30 results on '"Hoekstra EJ"'
Search Results
2. The Denver school-based adolescent hepatitis B vaccination program: a cost analysis with risk simulation.
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Deuson RR, Hoekstra EJ, Sedjo R, Bakker G, Melinkovich P, Daeke D, Hammer AL, Goldsman D, and Judson FN
- Abstract
OBJECTIVES: This study sought to compare the cost-effectiveness of a school-based hepatitis B vaccine delivery program with that of a vaccine delivery program associated with a network health maintenance organization (HMO). METHODS: The vaccination program enrolled 3359 sixth-grade students from 18 middle schools in Denver, Colo. Immunization status and direct and indirect program costs were compiled. The sensitivity of the outcomes was assessed by simulation methods. RESULTS: The per-dose cost-effectiveness ratio for the school-based delivery system was $31. This cost-effectiveness ratio remained stable when the model was simulated with costs that were underestimated or overestimated by 20%. In the network HMO, the direct cost per dose was $68 and the societal cost was $118 when the child's father worked full-time and the mother worked part-time. There is less than a 5% chance that the network HMO-based vaccination program could be more cost-effective than the school-based program. CONCLUSIONS: The cost per dose of the school-based program was significantly less than that of the network HMO-based program, because in the school program government-purchased vaccine was available at a lower cost and parents did not incur work-loss costs. [ABSTRACT FROM AUTHOR]
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- 1999
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3. Impact of a large-scale immunization initiative in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
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Hoekstra EJ, LeBaron CW, Megaloeconomou Y, Guerrero H, Byers C, Johnson-Partlow T, Lyons B, Mihalek E, Devier J, Mize J, Hoekstra, E J, LeBaron, C W, Megaloeconomou, Y, Guerrero, H, Byers, C, Johnson-Partlow, T, Lyons, B, Mihalek, E, Devier, J, and Mize, J
- Abstract
Context: Inner-city immunization rates have lagged behind those in other areas of the country.Objective: To evaluate the impact of an initiative linking immunization with distribution of food vouchers in the inner city.Design: Retrospective analysis of immunization data gathered in 1996 and 1997.Setting: Nineteen Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) sites serving 30% of the Chicago, III, birth cohort.Participants: A total of 16581 children 24 months old or younger.Interventions: Voucher incentives (varying frequency of food voucher issuance based on immunization status) and assessment of immunization status and referral to immunization provider.Main Outcome Measures: Age-appropriate immunization rates and WIC enrollment rates.Results: During the 15-month period of evaluation, immunization rates increased from 56% to 89% at sites performing voucher incentives. The proportion of children needing voucher incentives declined from 51% to 12%. Sites performing assessment and referral, but not providing voucher incentives, showed no evidence of improvement in immunization coverage. No difference was observed in enrollment rates between sites performing voucher incentives and those that did not.Conclusion: Applied in a large-scale, programmatic fashion, voucher incentives in WIC can rapidly increase and sustain high childhood immunization rates in an inner-city population. [ABSTRACT FROM AUTHOR]- Published
- 1998
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4. Physical work load and the onset of maternity leave.
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Koemeester AP, Leegwater A, Broersen JPJ, and Hoekstra EJ
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This study assesses the impact of performing physical job tasks at work during pregnancy. A prospective follow-up study was conducted among nurses and office workers. At 15 weeks of gestation, all participants were asked to describe their regular job tasks, the physical activities involved and their exposure to other occupational stressors. The physical activities identified were walking, standing, lifting, stooping, squatting, and sitting. Job adaptations were frequently realized for nurses. Despite these adaptations, from 23 weeks of gestation, and on, significantly more nurses had stopped working compared to office workers. From this point in gestation 44% of the nurses were performing their work as usual compared to 75% of the office workers. These results suggest that, if appropriate job adaptations are not possible, the onset of maternity leave should be regulated according to the level of physical effort required by the work. In addition, withdrawal from work due to the combination of pregnancy and physical workload could be minimized by a change in job tasks from the fifth month of gestation, allowing only office duties from then on. [ABSTRACT FROM AUTHOR]
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- 1997
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5. Experience in global measles control, 1990-2001.
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Henao-Restrepo A, Strebel P, Hoekstra EJ, Birmingham M, and Bilous J
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Worldwide during the 1980s remarkable progress was made in controlling measles through increasing routine measles vaccination to nearly 80%. In 2000, an estimated 777,000 measles deaths occurred, of which 452,000 were in the African Region of the World Health Organization (WHO). In 2001, WHO and the United Nations Children's Fund published a 5-year strategic plan to reduce measles mortality by half by 2005. Strategies include providing a second opportunity for measles immunization to all children through nationwide supplementary immunization activities, increasing routine vaccination coverage, and improving surveillance with laboratory confirmation of suspected measles cases. In 2000, over 100 million children received a dose of measles vaccine through supplementary immunization activities, a number projected to increase during 2002-2005. Current systems for monitoring measles vaccination coverage and disease burden must be improved to accurately assess progress toward measles control goals. Copyright © 2003 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]
- Published
- 2003
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6. Has the 2005 measles mortality reduction goal been achieved? A natural history modelling study.
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Wolfson LJ, Strebel PM, Gacic-Dobo M, Hoekstra EJ, McFarland JW, Hersh BS, and Measles Initiative
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- 2007
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7. Analysis of PBT and PET cyclic oligomers in extracts of coffee capsules and food simulants by a HPLC-UV/FLD method.
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Alberto Lopes J, Tsochatzis ED, Karasek L, Hoekstra EJ, and Emons H
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- Chromatography, High Pressure Liquid, Cyclization, Polyesters chemistry, Polyesters isolation & purification, Polyethylene Terephthalates chemistry, Polyethylene Terephthalates isolation & purification, Coffee chemistry, Food Analysis methods, Food Contamination analysis, Food Packaging, Polyesters analysis, Polyethylene Terephthalates analysis, Polymerization
- Abstract
A HPLC-UV/FLD method was validated for the quantification of six polyethylene terephthalate (PET) and four polybutylene terephthalate (PBT) oligomers. PBT oligomers are EU regulated, while the PET ones are considered non-intentionally added substances (NIAS). LOQs were higher than 0.4 and 3.5 μg kg
-1 for the simulants and in the polymer extracts, respectively. Recoveries ranged from 95 to 114 % with RSDs below 12%. Migration testing of PBT and polypropylene coffee capsules were performed with H2 O and simulant C, and extracts were obtained with accelerated solvent extraction (ASE). For the latter legislative limits weren't surpassed. As no migration limits are existing for the analytes, both EFSA's toxicological threshold of concern (TTC) and sum of oligomers approaches were applied. The majority of oligomers were below the TTC (90 µg/person/day), but the limit value of 50 µg/kg food was surpassed for some capsules, which indicates a significant intake in both single and multiple consumption., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
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8. Quantification of PET cyclic and linear oligomers in teabags by a validated LC-MS method - In silico toxicity assessment and consumer's exposure.
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Tsochatzis ED, Alberto Lopes J, Kappenstein O, Tietz T, and Hoekstra EJ
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- Computer Simulation, Dimerization, Food Contamination analysis, Mutagenicity Tests, Polyethylene Terephthalates chemistry, Reproducibility of Results, Tea, Chromatography, High Pressure Liquid methods, Food Packaging, Mass Spectrometry methods, Polyethylene Terephthalates analysis, Polyethylene Terephthalates toxicity
- Abstract
Determination of polyethylene terephthalate (PET) dimer up to heptamer 1st series cyclic oligomers, applying an LC-qTOF-MS method, has been developed and validated. Recoveries ranged between 80 and 112% with RSDs lower than 15%. An innovative semi-quantitative approach has been applied for 2nd and 3rd series cyclic oligomers, using the closest structural-similar 1st series cyclic oligomer standard as analytical reference. Oligomers from the three series were quantified in PET teabags after migration experiments with water and food simulants C (20% v/v ethanol in water) and D1 (50% v/v ethanol in water). No legal migration limits exist currently for these substances. In silico genotoxicity assessment of all identified oligomers has been performed and showed no genotoxicity alert for linear or cyclic molecules. Exposure assessment was performed using EFSA's approach on the total sum of migrating oligomers and on toxicological threshold-of-concern. Amounts found in water were in some cases significantly higher than the respective limits, especially in the worst-case scenario of multiple consumption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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9. Lmx1b Influences Correct Post-mitotic Coding of Mesodiencephalic Dopaminergic Neurons.
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Wever I, Largo-Barrientos P, Hoekstra EJ, and Smidt MP
- Abstract
The Lim Homeobox transcription factor 1 beta (LMX1b) has been identified as one of the transcription factors important for the development of mesodiencephalic dopaminergic (mdDA) neurons. During early development, Lmx1b is essential for induction and maintenance of the Isthmic Organizer (IsO), and genetic ablation results in the disruption of inductive activity from the IsO and loss of properly differentiated mdDA neurons. To study the downstream targets of Lmx1b without affecting the IsO, we generated a conditional model in which Lmx1b was selectively deleted in Pitx3 -expressing cells from embryonic day (E)13 onward. Supporting previous data, no significant changes could be observed in general dopamine (DA) marks, like Th, Pitx3 and Vmat2 at E14.5. However, in depth analysis by means of RNA-sequencing revealed that Lmx1b is important for the mRNA expression level of survival factors En1 and En2 and for the repression of mdDA subset mark Ahd2 during (late) development. Interestingly, the regulation of Ahd2 by Lmx1b was found to be Pitx3 independent, since Pitx3 mRNA levels were not altered in Lmx1b conditional knock-outs (cKOs) and Ahd2 expression was also up-regulated in Lmx1b/Pitx3 double mutants compared to Pitx3 mutants. Further analysis of Lmx1b cKOs showed that post-mitotic deletion of Lmx1b additional leads to a loss of TH+ cells at 3 months age both in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Remarkably, different cell types were affected in the SNc and the VTA. While TH+AHD2+ cells were lost the SNc, TH+AHD2- neurons were affected in the VTA, reflected by a loss of Cck expression, indicating that Lmx1b is important for the survival of a sub-group of mdDA neurons.
- Published
- 2019
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10. Molecular marker differences relate to developmental position and subsets of mesodiencephalic dopaminergic neurons.
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Smits SM, von Oerthel L, Hoekstra EJ, Burbach JP, and Smidt MP
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- Animals, Dopaminergic Neurons cytology, Mice, Substantia Nigra cytology, Substantia Nigra embryology, Ventral Tegmental Area cytology, Ventral Tegmental Area embryology, Dopaminergic Neurons metabolism, Gene Expression Regulation, Developmental, Substantia Nigra metabolism, Ventral Tegmental Area metabolism
- Abstract
The development of mesodiencephalic dopaminergic (mdDA) neurons located in the substantia nigra compacta (SNc) and ventral tegmental area (VTA) follow a number of stages marked by distinct events. After preparation of the region by signals that provide induction and patterning, several transcription factors have been identified, which are involved in specifying the neuronal fate of these cells. The specific vulnerability of SNc neurons is thought to root in these specific developmental programs. The present study examines the positions of young postmitotic mdDA neurons to relate developmental position to mdDA subset specific markers. MdDA neurons were mapped relative to the neuromeric domains (prosomeres 1-3 (P1-3), midbrain, and hindbrain) as well as the longitudinal subdivisions (floor plate, basal plate, alar plate), as proposed by the prosomeric model. We found that postmitotic mdDA neurons are located mainly in the floorplate domain and very few in slightly more lateral domains. Moreover, mdDA neurons are present along a large proportion of the anterior/posterior axis extending from the midbrain to P3 in the diencephalon. The specific positions relate to some extent to the presence of specific subset markers as Ahd2. In the adult stage more of such subsets specific expressed genes are present and may represent a molecular map defining molecularly distinct groups of mdDA neurons.
- Published
- 2013
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11. Lmx1a encodes a rostral set of mesodiencephalic dopaminergic neurons marked by the Wnt/B-catenin signaling activator R-spondin 2.
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Hoekstra EJ, von Oerthel L, van der Heide LP, Kouwenhoven WM, Veenvliet JV, Wever I, Jin YR, Yoon JK, van der Linden AJ, Holstege FC, Groot Koerkamp MJ, and Smidt MP
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- Animals, Immunohistochemistry, In Situ Hybridization, LIM-Homeodomain Proteins genetics, Mice, Polymerase Chain Reaction, Transcription Factors genetics, Dopaminergic Neurons metabolism, LIM-Homeodomain Proteins metabolism, Transcription Factors metabolism
- Abstract
Recent developments in molecular programming of mesodiencephalic dopaminergic (mdDA) neurons have led to the identification of many transcription factors playing a role in mdDA specification. LIM homeodomain transcription factor Lmx1a is essential for chick mdDA development, and for the efficient differentiation of ES-cells towards a dopaminergic phenotype. In this study, we aimed towards a more detailed understanding of the subtle phenotype in Lmx1a-deficient (dreher) mice, by means of gene expression profiling. Transcriptome analysis was performed, to elucidate the exact molecular programming underlying the neuronal deficits after loss of Lmx1a. Subsequent expression analysis on brain sections, confirmed that Nurr1 is regulated by Lmx1a, and additional downstream targets were identified, like Pou4f1, Pbx1, Pitx2, C130021l20Rik, Calb2 and Rspo2. In line with a specific, rostral-lateral (prosomer 2/3) loss of expression of most of these genes during development, Nurr1 and C130021l20Rik were affected in the SNc of the mature mdDA system. Interestingly, this deficit was marked by the complete loss of the Wnt/b-catenin signaling activator Rspo2 in this domain. Subsequent analysis of Rspo2-/- embryos revealed affected mdDA neurons, partially phenocopying the Lmx1a mutant. To conclude, our study revealed that Lmx1a is essential for a rostral-lateral subset of the mdDA neuronal field, where it might serve a critical function in modulating proliferation and differentiation of mdDA progenitors through the regulation of the Wnt activator Rspo2.
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- 2013
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12. Release of bisphenol A from polycarbonate: a review.
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Hoekstra EJ and Simoneau C
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- Animals, Benzhydryl Compounds analysis, Benzhydryl Compounds toxicity, Cooking and Eating Utensils legislation & jurisprudence, Diffusion, Estrogens, Non-Steroidal analysis, Estrogens, Non-Steroidal toxicity, Europe, Food Packaging legislation & jurisprudence, Humans, Infant, Infant Food analysis, Infant, Newborn, Legislation, Food, Milk chemistry, Phenols analysis, Phenols toxicity, Plastics toxicity, Polymers chemistry, Polymers toxicity, Solubility, Water chemistry, Benzhydryl Compounds chemistry, Consumer Product Safety legislation & jurisprudence, Estrogens, Non-Steroidal chemistry, Food Contamination legislation & jurisprudence, Phenols chemistry, Plastics chemistry
- Abstract
The release of Bisphenol A (BPA) from polycarbonate baby bottles into food and food simulants is reviewed in the perspective of the current intensive discussions on the risks of this substance. Potential factors that have been reported to influence the release of BPA are reviewed. Unlike most polymers polycarbonate is hydrolyzed under alkaline conditions by scale formation, residual alkaline detergents and boiled water. Data suggest that brushing of the bottle did not raise the release of BPA. Claims that used bottles release more BPA than new bottles and that mineral composition of the aqueous food simulant affect release could not be substantiated. There are indications that aminolysis of polycarbonate by milk and ethanolysis of polycarbonate by 50% ethanol might take place under relevant test conditions. The relatively few migration data following the test conditions of European food contact material legislation, comply with the specific migration limit. Two test conditions were identified that reflect real use and exposure, and might cause higher release of BPA compared to the test conditions of European food contact material legislation. Further detailed studies are necessary to verify whether these two exposure scenarios are more severe.
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- 2013
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13. LMX1B is part of a transcriptional complex with PSPC1 and PSF.
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Hoekstra EJ, Mesman S, de Munnik WA, and Smidt MP
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- Animals, Cell Line, Gene Expression Regulation, Developmental, HSP70 Heat-Shock Proteins metabolism, Homeodomain Proteins metabolism, LIM-Homeodomain Proteins genetics, Mesencephalon embryology, Mesencephalon metabolism, Mice, Mice, Inbred C57BL, Neurogenesis, Neurons cytology, Neurons metabolism, Nuclear Proteins genetics, Nuclear Receptor Subfamily 4, Group A, Member 2 genetics, Nuclear Receptor Subfamily 4, Group A, Member 2 metabolism, PTB-Associated Splicing Factor, Protein Binding, RNA-Binding Proteins genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Transcription Factors genetics, Transcriptional Activation, LIM-Homeodomain Proteins metabolism, Nuclear Proteins metabolism, Protein Interaction Mapping, RNA-Binding Proteins metabolism, Transcription Factors metabolism
- Abstract
The LIM homeodomain transcription factor Lmx1b is essential for the development of the isthmic organizer and mesodiencephalic dopaminergic neurons. The uncoupling of Pitx3 and Th expression, in the Lmx1b null mutant, suggests that Lmx1b may act as a positional activator of the mdDA domain, eventually leading to properly differentiating mdDA neurons. In this study, we aimed to elucidate how Lmx1b functions mechanistically in this developmental process, by searching for molecular interactors of Lmx1b at the protein level. Initially, affinity-purification of LMX1B-HIS overexpressed protein in MN9D dopaminergic cells followed by mass-spectrometry analysis, resulted in the identification of PSPC1 protein as a possible binding partner of LMX1B. Subsequent immunoprecipitation experiments revealed an interaction between LMX1B and PSPC1 in a larger protein complex also containing PSF. This complex was observed in vitro and in vivo, and we hypothesize that, via PSF and PSPC1, LMX1B may be part of the previously identified Nurr1 transcriptional complex wherein interaction with the co-repressor PSF and the transcription factor Pitx3 is needed to drive expression of Nurr1 target genes in specifying the dopaminergic phenotype. Furthermore, we identified GRLF1, DHX9, MYO1C, HSP70 and TMPO as potential LMX1B interactors. DHX9 and GRLF1 are highly expressed in the developing mdDA neuronal field, and GRLF1 and MYO1C have both been linked to neurite outgrowth. The identification of these proteins suggests that Lmx1b may act directly in the transcriptional activation of Nurr1 target genes and be involved in other processes like neurite outgrowth as well.
- Published
- 2013
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14. Lmx1a is an activator of Rgs4 and Grb10 and is responsible for the correct specification of rostral and medial mdDA neurons.
- Author
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Hoekstra EJ, von Oerthel L, van der Linden AJ, Schellevis RD, Scheppink G, Holstege FC, Groot-Koerkamp MJ, van der Heide LP, and Smidt MP
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- Animals, Brain cytology, Brain embryology, Brain metabolism, Cell Line, GRB10 Adaptor Protein genetics, Gene Expression Profiling, Gene Expression Regulation, Developmental, LIM-Homeodomain Proteins genetics, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mutation, Oligonucleotide Array Sequence Analysis, RGS Proteins genetics, Transcription Factors genetics, Transcription, Genetic, Vesicular Monoamine Transport Proteins genetics, Vesicular Monoamine Transport Proteins metabolism, Dopaminergic Neurons metabolism, GRB10 Adaptor Protein metabolism, LIM-Homeodomain Proteins metabolism, RGS Proteins metabolism, Transcription Factors metabolism
- Abstract
The LIM homeodomain transcription factor Lmx1a is a very potent inducer of stem cells towards dopaminergic neurons. Despite several studies on the function of this gene, the exact in vivo role of Lmx1a in mesodiencephalic dopamine (mdDA) neuronal specification is still not understood. To analyse the genes functioning downstream of Lmx1a, we performed expression microarray analysis of LMX1A-overexpressing MN9D dopaminergic cells. Several interesting regulated genes were identified, based on their regulation in other previously generated expression arrays and on their expression pattern in the developing mdDA neuronal field. Post analysis through in vivo expression analysis in Lmx1a mouse mutant (dr/dr) embryos demonstrated a clear decrease in expression of the genes Grb10 and Rgs4, in and adjacent to the rostral and dorsal mdDA neuronal field and within the Lmx1a expression domain. Interestingly, the DA marker Vmat2 was significantly up-regulated as a consequence of increased LMX1A dose, and subsequent analysis on Lmx1a-mutant E14.5 and adult tissue revealed a significant decrease in Vmat2 expression in mdDA neurons. Taken together, microarray analysis of an LMX1A-overexpression cell system resulted in the identification of novel direct or indirect downstream targets of Lmx1a in mdDA neurons: Grb10, Rgs4 and Vmat2., (© 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)
- Published
- 2013
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15. One country, two worlds - the health disparity in China.
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Meng Q, Zhang J, Yan F, Hoekstra EJ, and Zhuo J
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- Adult, China epidemiology, Economic Development, Emigration and Immigration, Female, Health Care Reform, Health Status Indicators, Healthcare Disparities, Humans, Rural Health, Young Adult, Health Status Disparities
- Abstract
As result of its spectacular economic growth, millions of Chinese have been lifted out of poverty, making China a model for impoverished countries. Although, for many, economic growth has led to prosperity, ever-growing disparities exist between those who have benefited from the economic advancement and those left behind. Massive gaps in development exist between: regions, urban and rural and social groups. This contribution is to develop a detailed understanding of the health disparity in China by examining the discrepancies in major health indicators. Current efforts to reduce the disparities, and its challenges, opportunities and global implications are also assessed.
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- 2012
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16. Spatial and temporal lineage analysis of a Pitx3-driven Cre-recombinase knock-in mouse model.
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Smidt MP, von Oerthel L, Hoekstra EJ, Schellevis RD, and Hoekman MF
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- Animals, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit Disorder with Hyperactivity metabolism, Attention Deficit Disorder with Hyperactivity pathology, Depression genetics, Depression metabolism, Depression pathology, Diencephalon cytology, Dopaminergic Neurons cytology, Gene Knock-In Techniques, Genes, Reporter, Homeodomain Proteins genetics, Humans, Integrases genetics, Integrases metabolism, Mice, Mice, Transgenic, Parkinson Disease genetics, Parkinson Disease metabolism, Parkinson Disease pathology, Protein Structure, Tertiary, Schizophrenia genetics, Schizophrenia metabolism, Schizophrenia pathology, Transcription Factors genetics, Cell Differentiation physiology, Cell Lineage physiology, Diencephalon embryology, Dopaminergic Neurons metabolism, Genetic Loci physiology, Homeodomain Proteins biosynthesis, Transcription Factors biosynthesis
- Abstract
Development and function of mesodiencephalic dopaminergic (mdDA) neurons has received a lot of scientific interest since these neurons are critically involved in neurological diseases as Parkinson and psychiatric diseases as schizophrenia, depression and attention deficit hyperactivity disorder (ADHD). The understanding of the molecular processes that lead to normal development and function of mdDA neurons has provided insight in the pathology and provided critical information on new treatment paradigms. In order to be able to study specific genetic ablation in mdDA neurons a new tools was developed that drives Cre-recombinase under the control of the Pitx3 locus. The Pitx3 gene is well known for its specific expression in mdDA neurons and is present at the onset of terminal differentiation. Analysis of newly generated Pitx3-Cre knock-in mice shows that Cre expression, measured through the activation of eYfp by removal of a "Stop" signal (LoxP-Stop-LoxP-eYfp reporter mouse), is present at the onset of terminal differentiation and mimics closely the native Pitx3 expression domain. In conclusion, we present here a new Cre-driver mouse model to be used in the restricted ablation of interesting genes in mdDA neurons in order to improve our understanding of the underlying molecular programming.
- Published
- 2012
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17. Phox2b influences the development of a caudal dopaminergic subset.
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Hoekstra EJ, von Oerthel L, van der Linden AJ, and Smidt MP
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- Animals, Dopaminergic Neurons metabolism, Female, Gene Expression Regulation, Developmental, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Mice, Mice, Inbred C57BL, Mutation, Neurogenesis genetics, Pregnancy, Spinal Nerve Roots metabolism, Spinal Nerve Roots physiology, Transcription Factors genetics, Transcription Factors metabolism, Trigeminal Caudal Nucleus metabolism, Trigeminal Caudal Nucleus physiology, Ventral Tegmental Area metabolism, Ventral Tegmental Area physiology, Dopaminergic Neurons physiology, Homeodomain Proteins physiology, Neurogenesis physiology, Transcription Factors physiology
- Abstract
The developing mesodiencephalic dopaminergic (mdDA) neuronal field can be subdivided into several molecularly distinct domains that arise due to spatiotemporally distinct origins of the neurons and distinct transcriptional pathways controlling these neuronal subsets. Two large anatomically and functionally different subdomains are formed that eventually give rise to the SNc and VTA, but more subsets exist which require detailed characterization in order to better understand the development of the functionally different mdDA subsets, and subset-specific vulnerability. In this study, we aimed to characterize the role of transcription factor Phox2b in the development of mdDA neurons. We provide evidence that Phox2b is co-expressed with TH in a dorsal-caudal subset of neurons in the mdDA neuronal field during embryonic development. Moreover, Phox2b transcripts were identified in FAC-sorted Pitx3 positive neurons. Subsequent analysis of Phox2b mutant embryos revealed that in the absence of Phox2b, a decrease of TH expression occurred specifically in the midbrain neuronal subset that normally co-expresses Phox2b with TH. Our data suggest that Phox2b is, next to the known role in the development of the oculomotor complex, involved in the development of a specific caudal mdDA neuronal subset.
- Published
- 2012
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18. Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons.
- Author
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Jacobs FM, Veenvliet JV, Almirza WH, Hoekstra EJ, von Oerthel L, van der Linden AJ, Neijts R, Koerkamp MG, van Leenen D, Holstege FC, Burbach JP, and Smidt MP
- Subjects
- Analysis of Variance, Animals, Calcium-Binding Proteins, Cell Differentiation drug effects, Cell Differentiation physiology, Female, Fluorescent Antibody Technique, Gene Regulatory Networks physiology, Genotype, In Situ Hybridization, Intercellular Signaling Peptides and Proteins metabolism, Mice, Mice, Knockout, Microarray Analysis, Neurons physiology, Nuclear Receptor Subfamily 4, Group A, Member 2 metabolism, Polymerase Chain Reaction, Pregnancy, Receptors, Dopamine D2 metabolism, Transcription Factors deficiency, Diencephalon cytology, Diencephalon embryology, Gene Regulatory Networks drug effects, Homeodomain Proteins metabolism, Neurons metabolism, Transcription Factors metabolism, Tretinoin pharmacology
- Abstract
Development of meso-diencephalic dopamine (mdDA) neurons requires the combined actions of the orphan nuclear receptor Nurr1 and the paired-like homeobox transcription factor Pitx3. Whereas all mdDA neurons require Nurr1 for expression of Th and survival, dependence on Pitx3 is displayed only by the mdDA subpopulation that will form the substantia nigra (SNc). Previously, we have demonstrated that Pitx3(-/-) embryos lack the expression of the retinoic acid (RA)-generating enzyme Ahd2, which is normally selectively expressed in the Pitx3-dependent DA neurons of the SNc. Restoring RA signaling in Pitx3(-/-) embryos revealed a selective dependence of SNc neurons on the presence of RA for differentiation into Th-positive neurons and maintenance throughout embryonic development. Whereas these data are suggestive of an important developmental role for RA in neurons of the SNc, it remained unclear whether other Nurr1 and Pitx3 target genes depend on RA signaling in a manner similar to Th. In the search for genes that were affected in Pitx3-deficient mdDA neurons and restored upon embryonic RA treatment, we provide evidence that Delta-like 1, D2R (Drd2) and Th are regulated by Pitx3 and RA signaling, which influences the mdDA terminal differentiated phenotype. Furthermore, we show that regulation of Ahd2-mediated RA signaling represents only one aspect of the Pitx3 downstream cascade, as Vmat2, Dat, Ahd2 (Aldh1a1), En1, En2 and Cck were unaffected by RA treatment and are (subset) specifically modulated by Pitx3. In conclusion, our data reveal several RA-dependent and -independent aspects of the Pitx3-regulated gene cascade, suggesting that Pitx3 acts on multiple levels in the molecular subset-specification of mdDA neurons.
- Published
- 2011
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19. Measles mortality reduction contributes substantially to reduction of all cause mortality among children less than five years of age, 1990-2008.
- Author
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van den Ent MM, Brown DW, Hoekstra EJ, Christie A, and Cochi SL
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- Child, Preschool, Global Health, Humans, Infant, Infant, Newborn, Measles prevention & control, Population Surveillance, Time Factors, Vaccination, Child Mortality trends, Infant Mortality trends, Measles mortality, Measles Vaccine administration & dosage
- Abstract
Background: The Millennium Development Goal 4 (MDG4) to reduce mortality in children aged <5 years by two-thirds from 1990 to 2015 has made substantial progress. We describe the contribution of measles mortality reduction efforts, including those spearheaded by the Measles Initiative (launched in 2001, the Measles Initiative is an international partnership committed to reducing measles deaths worldwide and is led by the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization)., Methods: We used published data to assess the effect of measles mortality reduction on overall and disease-specific global mortality rates among children aged <5 years by reviewing the results from studies with the best estimates on causes of deaths in children aged 0-59 months., Results: The estimated measles-related mortality among children aged <5 years worldwide decreased from 872,000 deaths in 1990 to 556,000 in 2001 (36% reduction) and to 118,000 in 2008 (86% reduction). All-cause mortality in this age group decreased from >12 million in 1990 to 10.6 million in 2001 (13% reduction) and to 8.8 million in 2008 (28% reduction). Measles accounted for about 7% of deaths in this age group in 1990 and 1% in 2008, equal to 23% of the global reduction in all-cause mortality in this age group from 1990 to 2008., Conclusions: Aggressive efforts to prevent measles have led to this remarkable reduction in measles deaths. The current funding gap and insufficient political commitment for measles control jeopardizes these achievements and presents a substantial risk to achieving MDG4., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)
- Published
- 2011
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20. Impact of supplementary immunization activities in measles-endemic areas: a case study from Guangxi, China.
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Zhuo J, Geng W, Hoekstra EJ, Zhong G, Liang X, and Zhang J
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- Adolescent, Child, Child, Preschool, China epidemiology, Humans, Immunization Schedule, Risk Factors, Socioeconomic Factors, Endemic Diseases, Immunization Programs, Measles epidemiology, Measles prevention & control, Measles Vaccine administration & dosage
- Abstract
Because of limited resources, each year during the period from 1999 through 2007, only about one-quarter of the 111 counties in Guangxi province were selected by means of risk assessment to participate in Supplementary Immunization Activities (SIAs), targeting children aged 8 months to 14 years during 1999-2003 and 8 months to 10 years during 2004-2007. Approximately 2 million doses of measles vaccines were administrated each year during SIAs. Estimated from the National Notifiable Diseases Surveillance System, with a reliable internal consistency over years, the average annual incidences of measles before SIAs (1993-1998), during the first phase (1999-2003), and during the second phase (2004-2007) were 16.05, 9.10, and 2.46 cases per 100,000, respectively. The overall provincewide annual incidence decreased by 84.67%, from 12.12 cases per 100,000 in 2000 to 2.10 cases per 100,000 in 2007. The percentage of counties with annual incidence ≥10 cases per 100,000 decreased from 55% in 1993 to <1% in 2007. Compared with the pre-SIA period, the greatest decrease in annual incidence was 83.93% for the 10-14.9-year-old group and the smallest decrease was 46.16% for children <1 year old. The multiple-year SIAs targeting children in selected high-risk counties were effective in controlling measles in mountainous, impoverished, and multiethnic measles-endemic areas., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
21. Measles supplementary immunization activities and GAVI funds as catalysts for improving injection safety in Africa.
- Author
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Hoekstra EJ, van den Ent MM, Dao H, Khalaf H, and Salovaara A
- Subjects
- Financing, Government economics, Global Health, Humans, Immunization Programs economics, Immunization Programs supply & distribution, Injections adverse effects, Measles epidemiology, Medical Waste Disposal, Syringes supply & distribution, United Nations, Disposable Equipment, Measles prevention & control, Measles Vaccine administration & dosage, Syringes adverse effects
- Abstract
Background: In 2000, reuse of disposable syringes and inadequately sterilized syringes resulted in 39% of all injections being unsafe, causing 22 million infections. We describe the contribution of measles supplemental immunization activities (SIAs) and Global Alliance for Vaccines and Immunisation (GAVI) funding in replacing disposable and sterilizable syringes with auto-disable (AD) syringes to improve injection safety in 39 African countries., Methods: We assessed trends in nationwide introduction of AD syringes against measles catch-up SIAs and GAVI funding using World Health Organization/United Nations Children's Fund (UNICEF) Joint Reporting Form for Immunization and UNICEF supply data., Results: In 19 (49%) of 39 countries, the measles program catalyzed the introduction of injection safety equipment, including AD syringes and safety boxes, training, and procurement of safety equipment during SIAs. GAVI was catalytic through financial support in 14 countries (36%) for including safe injection equipment in routine immunization. Additionally, GAVI funded 21 countries that had already introduced AD syringes in their national program. UNICEF AD syringe shipments to sub-Saharan Africa increased from 11 million to 461 million from 1997 to 2008. All 39 countries stopped using sterilizable syringes by 2004., Conclusions: The measles mortality reduction program and GAVI complemented each other in improving injection safety. All countries continued with AD syringes for immunization after measles catch-up SIAs and GAVI funding ended., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
22. Innovative use of surveillance data to harness political will to accelerate measles elimination: experience from Guangxi, China.
- Author
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Zhuo J, Hoekstra EJ, Zhong G, Liu W, Zheng Z, and Zhang J
- Subjects
- China epidemiology, Humans, Incidence, Population Surveillance, Time Factors, Immunization Programs organization & administration, Measles epidemiology, Measles prevention & control, Measles Vaccine administration & dosage, Politics
- Abstract
The major challenge for measles elimination is to harness sufficient political will to provide the necessary financial and human resources. This is particularly relevant for local governments (at county and township levels in China) and communities that generally have not accepted measles as a serious health burden and thus have not made its prevention a high priority. An effort has been made to use surveillance data to harness political will and overcome or mitigate the shortage of resources in the impoverished province of Guangxi, one of China's 31 administrative divisions. A comprehensive information system collecting data pertaining to Expanded Program on Immunization (EPI-info) was refined to align with China's political system and translate international and national commitments into sustainable local actions. The EPI-info has proved an effective tool in identifying high-risk areas, strengthening routine immunization services, conducting mass measles immunization campaigns, and catalyzing capacity building at both county and local community levels. We outline the principles and operational features of the EPI-info and the rationale and steps taken to refine it., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
23. Reuse prevention syringes for reconstitution of lyophilized vaccines: Operational study and UNICEF plans for expanding introduction.
- Author
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Fleming JA, Hoekstra EJ, Moniaga V, Widjaya A, Soepardi J, Supartha N, Salovaara A, Khamassi S, and Nelson C
- Subjects
- Freeze Drying, Humans, Immunization Programs standards, Injections standards, Safety Management methods, United Nations, Disposable Equipment standards, Equipment Reuse standards, Immunization instrumentation, Injections instrumentation, Syringes standards, Vaccines administration & dosage
- Abstract
Since the 1990s, the United Nation's Children's Fund has encouraged injection safety for immunizations through bundling vaccines with appropriate amounts of supporting equipment and by supplying autodisable (AD) syringes for injections. However, poor vaccine reconstitution practices continue to be reported worldwide. By 2009, UNICEF will begin to phase out the distribution of standard disposable syringes for vaccine reconstitution and replace them with reuse prevention (RUP) syringes, with a full transition expected by the end of 2010. A field evaluation in Indonesia was conducted to identify introduction requirements, issues with healthcare worker training and acceptance, and RUP syringe performance and safety. Managers and health workers felt that RUP syringes improved injection safety and fit easily into country logistical systems. Healthcare workers felt they were intuitive to use, but recommended special training. The integration of RUP reconstitution syringes by UNICEF could increase injection safety by preventing the reuse of syringes and reducing vaccine contamination.
- Published
- 2009
- Full Text
- View/download PDF
24. Reducing measles mortality, reducing child mortality.
- Author
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Hoekstra EJ, McFarland JW, Shaw C, and Salama P
- Subjects
- Child, Preschool, Health Priorities, Humans, Infant, Infant, Newborn, Measles drug therapy, Measles mortality, Vitamin A therapeutic use, Child Welfare, Developing Countries, Global Health, Goals, Measles prevention & control, Measles Vaccine
- Published
- 2006
- Full Text
- View/download PDF
25. Review of concentrations and chemistry of trichloroacetate in the environment.
- Author
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Hoekstra EJ
- Subjects
- Biodegradation, Environmental, Trees metabolism, Environment, Environmental Pollutants analysis, Trichloroacetic Acid analysis, Trichloroacetic Acid chemistry
- Abstract
This paper reviews the concentrations of trichloroacetate (TCA) in the atmosphere-plant-soil system. Data originate mainly from Europe. The median TCA concentration in rainwater and canopy drip decreased until 1995. From then the median TCA concentration in rainwater remains rather constant while for canopy drip later data are not available. The same seems to hold for concentrations in air although a very limited data set is available. The median concentrations in coniferous needles and groundwater are constant for the period observed. The median TCA concentrations in soil decreased until 1992 and then remained constant.The TCA formation from chlorinated solvents in the atmosphere may explain a substantial percentage of the TCA amount in the atmosphere. The TCA concentrations in rainwater and canopy drip indicate that there will be other sources contributing to 10-50%. Waste incineration, biomass burning and natural formation in the marine boundary layer are potential candidate sources of TCA, but nothing can be said as yet on their TCA emission rates. Anthropogenic emissions of chlorine could also be a source.TCA can be formed from chlorinated solvents by biota. However, for coniferous trees the uptake of TCA from soil may be the predominant route. Biotic and abiotic reactions can cause to formation of TCA in soil, but also formation of TCA from chlorinated solvents by biota that excrete TCA, may contribute. Mass balance calculations of the bioactive soil top layer show that the production rate of TCA in certain soil types could be substantial. The mass balance calculations could not distinguish between natural and anthropogenic sources in soil.
- Published
- 2003
- Full Text
- View/download PDF
26. Determining measles-containing vaccine demand and supply: an imperative to support measles mortality reduction efforts.
- Author
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Costa A, Henao-Restrepo AM, Marie Hall S, Jarrett S, and Hoekstra EJ
- Subjects
- Child, Preschool, Forecasting, Humans, Infant, Mass Vaccination economics, Measles economics, Measles Vaccine economics, United Nations, Vaccination economics, Vaccination methods, World Health Organization, Mass Vaccination methods, Measles prevention & control, Measles Vaccine supply & distribution
- Abstract
Measles remains a major cause of mortality with an estimated 745,000 deaths in 2001. The timely, sustained, and uninterrupted supply of affordable vaccines is critical for global efforts to reduce measles mortality. The measles vaccine supply needs to be considered in the context of vaccine security. In 2000, the World Health Organization (WHO) and United Nations Children's Fund (UNICEF) issued a number of new recommendations for measles control that resulted in a two-fold increase in the number of measles-containing vaccine (MCV) doses administered between 2000 and 2002. Any additional increments in mass campaigns must be duly planned and have time lines so that vaccine production capacities are increased to optimal levels. The cornerstone of vaccine security efforts remains at the country level. WHO and UNICEF, with major partners, will review progress on measles mortality reduction and assess the feasibility of global measles eradication. Strong collaboration by all key stakeholders will be invaluable.
- Published
- 2003
- Full Text
- View/download PDF
27. Excluding polio in areas of inadequate surveillance in the final stages of eradication in China.
- Author
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Hoekstra EJ, Chai F, Wang XJ, Zhang XL, Yu JJ, and Bilous J
- Subjects
- Adolescent, Child, Child, Preschool, China epidemiology, Cluster Analysis, Feces microbiology, Humans, Infant, Male, Paralysis virology, Poliomyelitis diagnosis, Poliomyelitis epidemiology, Poliovirus isolation & purification, Poliomyelitis prevention & control, Population Surveillance methods
- Abstract
In 1996, China adopted a virological classification of acute flaccid paralysis (AFP) cases for its surveillance system. Only AFP cases with wild poliovirus in stool specimens are confirmed as polio. Cases with adequate stool specimens that are negative for wild poliovirus are not counted. This paper describes a methodology to rule out poliomyelitis in AFP cases with inadequate stool specimens. National surveillance data were analysed using dot maps to detect clusters of AFP cases with high-risk factors for poliomyelitis. The surveillance system and vaccine coverage were assessed during field investigations. Four clusters of AFP cases were identified, but no poliomyelitis cases. Programmatic failures in the identified high-risk areas included low vaccination rates, poor stool specimen collection and inadequate AFP surveillance. Programme strategies were implemented to correct the identified failures. Use of this methodology provides strong evidence consistent with the absence of wild poliovirus in China.
- Published
- 2000
28. Does reminder-recall augment the impact of voucher incentives on immunization rates among inner-city infants enrolled in WIC? Special Supplemental Program for Women, Infants, and Children.
- Author
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Hoekstra EJ, LeBaron CW, and Johnson-Partlow T
- Subjects
- Chicago, Humans, Infant, Program Evaluation, United States, Immunization Programs statistics & numerical data, Poverty Areas, Public Assistance, Reminder Systems economics
- Abstract
Inner-city infants (n = 565) enrolled in the WIC program were randomly assigned at 6 months of age to either of 2 groups: (1) voucher incentive (frequency of issuance of food vouchers based on immunization status) plus reminder-recall (calls and/or letters to families of under-vaccinated children) or (2) voucher incentive alone. At 12 months, both groups' immunization levels were high and not significantly different: 80% +/- 4% versus 79% +/- 5% (P =.749).
- Published
- 1999
- Full Text
- View/download PDF
29. Mass balance of trichloroacetic acid in the soil top layer
- Author
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Hoekstra EJ, de Leer EW, and Brinkman UA
- Abstract
Since the ban on the use of trichloroacetic acid (TCAA) as a herbicide in several countries, TCAA is still found ubiquitously in the environment. The presence of TCAA nowadays is suggested to originate mainly from the atmospheric degradation of tetrachloroethene. Our mass balance calculations indicate that this may be true for the presence of TCAA in the atmosphere. However, our mass balance calculations also provide tentative evidence for the formation of TCAA in soil. If our calculated production fluxes are realistic estimates, a very large source of TCAA in soil has been identified.
- Published
- 1999
- Full Text
- View/download PDF
30. Monitoring of exposure to benomyl in nursery workers.
- Author
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Hoekstra EJ, Kiefer M, and Tepper A
- Subjects
- Adult, Air Pollutants, Occupational analysis, Benzimidazoles urine, Carbamates urine, Crops, Agricultural, Female, Florida, Humans, Male, Rural Health, Skin chemistry, Benomyl analysis, Environmental Monitoring, Fungicides, Industrial analysis, Occupational Exposure
- Abstract
We compared urinary levels of the metabolite methyl-5-hydroxy-2-benzimidazole carbamate (5-HBC) among nursery workers exposed to the fungicide benomyl (specifically Benlate 50 DF [DuPont, Wilmington, DE]) and workers not exposed to benomyl. Environmental exposures were quantitated from gloves, body patches, and air samples collected with area and personal monitors. The median concentration of 5-HBC in the urine of benomyl-exposed workers was 23.8 mumol of 5-HBC per mole of creatinine. No 5-HBC was detected in the reference group. Industrial hygiene results and biological monitoring findings indicate that use of Benlate 50 DF in the ornamental industry can lead to absorption of the active ingredient, benomyl. Weighing, mixing, and application activities involved the highest exposures. Dermal contact appeared to be the primary route of exposure.
- Published
- 1996
- Full Text
- View/download PDF
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