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Showing papers by "Research Triangle Park published in 2008"


Journal ArticleDOI
06 Nov 2008-Nature
TL;DR: Despite low average levels of genetic differentiation among Europeans, there is a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans.
Abstract: Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres.

1,460 citations


Journal ArticleDOI
18 Jul 2008-Immunity
TL;DR: It is found that the development of Th17 and Foxp3(+) Treg cells was associated in immune responses and molecular antagonism and plasticity of Treg and Th17 cell programs are demonstrated.

1,087 citations


Journal ArticleDOI
TL;DR: Using a sensitive qRT-PCR platform, experimental validation is used to reveal how the deregulated brain microRNAs are biomarkers for known and novel pathways in AD pathogenesis related to amyloid processing, neurogenesis, insulin resistance, and innate immunity.
Abstract: MicroRNAs have essential functional roles in brain development and neuronal specification but their roles in neurode- generative diseases such as Alzheimer's disease (AD) is unknown. Using a sensitive qRT-PCR platform we identified regional and stage-specific deregulation of miRNA expression in AD patient brains. We used experimental validation in addition to literature to reveal how the deregulated brain microRNAs are biomarkers for known and novel pathways in AD pathogenesis related to amyloid processing, neurogenesis, insulin resistance, and innate immunity. We additionally recovered miRNAs from cerebrospinal fluid and discovered AD-specific miRNA changes consistent with their role as potential biomarkers of disease.

879 citations


Journal ArticleDOI
TL;DR: The use of BMI as a measure of obesity can introduce misclassification problems that may result in important bias in estimating the effects related to obesity.
Abstract: Body mass index (BMI) has various deficiencies as a measure of obesity, especially when the BMI measure is based on self-reported height and weight. BMI is an indirect measure of body fat compared with more direct approaches such as bioelectrical impedance. Moreover, BMI does not necessarily reflect the changes that occur with age. The proportion of body fat increases with age, whereas muscle mass decreases, but corresponding changes in height, weight and BMI may not reflect changes in body fat and muscle mass. Both the sensitivity and specificity of BMI have been shown to be poor. Additionally, the relation between BMI and percentage of body fat is not linear and differs for men and women. The consequences of the errors in the measurement of obesity with BMI depend on whether they are differential or nondifferential. Differential misclassification, a potentially greater problem in case-control and cross-sectional studies than in prospective cohort studies, can produce a bias toward or away from the null. Nondifferential misclassification produces a bias toward the null for a dichotomous exposure; for measures of exposure that are not dichotomous, the bias may be away from the null. In short, the use of BMI as a measure of obesity can introduce misclassification problems that may result in important bias in estimating the effects related to obesity.

821 citations


Journal ArticleDOI
TL;DR: In this paper, a systematic review of bridgeless power factor correction (PFC) boost rectifiers, also called dual-boost PFC rectifiers is presented, where loss analysis and experimental efficiency evaluation for both CCM and DCM/CCM boundary operations are provided.
Abstract: In this paper, a systematic review of bridgeless power factor correction (PFC) boost rectifiers, also called dual boost PFC rectifiers, is presented. Performance comparison between the conventional PFC boost rectifier and a representative member of the bridgeless PFC boost rectifier family is performed. Loss analysis and experimental efficiency evaluation for both CCM and DCM/CCM boundary operations are provided.

739 citations


Journal ArticleDOI
TL;DR: In this paper, the authors proposed an alternative to petroleum-derived fuels and chemicals using renewable energy sources such as biomass, which can also serve as a feedstock for the synthesis of a variety of industrial chemicals and polymers.
Abstract: Alternatives to petroleum-derived fuels and chemicals are being sought in an effort to improve air quality and increase energy security through development of novel technologies for the production of synthetic fuels and chemicals using renewable energy sources such as biomass. In this context, ethanol is being considered as a potential alternative synthetic fuel to be used in automobiles or as a potential source of hydrogen for fuel cells as it can be produced from biomass. Renewable ethanol can also serve as a feedstock for the synthesis of a variety of industrial chemicals and polymers. Currently, ethanol is produced primarily by fermentation of biomass-derived sugars, especially those containing six carbons, whereas 5-carbon sugars and lignin, which are also present in the biomass, remain unusable. Gasification of biomass to syngas (CO + H2), followed by catalytic conversion of syngas, could produce ethanol in large quantities. However, the catalytic conversion of syngas to ethanol remains challenging,...

725 citations


Journal ArticleDOI
TL;DR: NAFLD is associated with higher overall and liver-related mortality in the general US population and Liver disease is a significant cause of death among persons with NAFLD.

571 citations


Journal ArticleDOI
TL;DR: The performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples and the capability to perform sample preparation for bacterial infectious disease pathogen, methicillin-resistant Staphylococcus aureus and for human genomic DNA using magnetic beads are demonstrated.
Abstract: Point of care testing is playing an increasingly important role in improving the clinical outcome in health care management. The salient features of a point of care device are rapid results, integrated sample preparation and processing, small sample volumes, portability, multifunctionality and low cost. In this paper, we demonstrate some of these salient features utilizing an electrowetting-based Digital Microfluidic platform. We demonstrate the performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples. Using the same microfluidic cartridge, a 40-cycle real-time polymerase chain reaction was performed within 12 minutes by shuttling a droplet between two thermal zones. We further demonstrate, on the same cartridge, the capability to perform sample preparation for bacterial infectious disease pathogen, methicillin-resistant Staphylococcus aureus and for human genomic DNA using magnetic beads. In addition to rapid results and integrated sample preparation, electrowetting-based digital microfluidic instruments are highly portable because fluid pumping is performed electronically. All the digital microfluidic chips presented here were fabricated on printed circuit boards utilizing mass production techniques that keep the cost of the chip low. Due to the modularity and scalability afforded by digital microfluidics, multifunctional testing capability, such as combinations within and between immunoassays, DNA amplification, and enzymatic assays, can be brought to the point of care at a relatively low cost because a single chip can be configured in software for different assays required along the path of care.

559 citations


Journal ArticleDOI
TL;DR: This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGiv-C as a therapy for C IDP.
Abstract: Summary Background Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740. Findings During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33·5%, 95% CI 15·4–51·7; p=0·0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10·9 kPa, 4·6–17·2; p=0·0008) and the non-dominant hand (8·6 kPa, 2·6–14·6; p=0·005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0·011). The incidence of serious adverse events per infusion was 0·8% (9/1096) with IGIV-C versus 1·9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension. Interpretation This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP.

549 citations


Journal ArticleDOI
TL;DR: A minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract, is developed to improve reporting of abstracts of RCTs published in journal articles and conference proceedings.
Abstract: Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract

547 citations


Journal ArticleDOI
TL;DR: The genomewide association analysis again identified the APOE linkage disequilibrium region as the strongest genetic risk factor for AD.
Abstract: Objective To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs. Design Case-control study with replication. Setting Memory referral clinics in Canada and the United Kingdom. Participants The hypothesis-generating data set consisted of 753 individuals with AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria recruited from 9 memory referral clinics in Canada and 736 ethnically matched control subjects; control subjects were recruited from nonbiological relatives, friends, or spouses of the patients and did not exhibit cognitive impairment by history or cognitive testing. The follow-up data set consisted of 418 AD cases and 249 nondemented control cases from the United Kingdom Medical Research Council Genetic Resource for Late-Onset AD recruited from clinics at Cardiff University, Cardiff, Wales, and King's College London, London, England. Main Outcome Measures Odds ratios and 95% confidence intervals for association of SNPs with AD by logistic regression adjusted for age, sex, education, study site, and French Canadian ancestry (for the Canadian data set). Hazard ratios and 95% confidence intervals from Cox proportional hazards regression for age at onset with similar covariate adjustments. Results Unadjusted, SNP RS4420638 within APOC1 was strongly associated with AD due entirely to linkage disequilibrium with APOE. In the multivariable adjusted analyses, 3 SNPs within the top 120 by P value in the logistic analysis and 1 in the Cox analysis of the Canadian data set provided additional evidence for association at P < .05 within the United Kingdom Medical Research Council data set: RS7019241 (GOLPH2), RS10868366 (GOLPH2), RS9886784 (chromosome 9), and RS10519262 (intergenic between ATP8B4 and SLC27A2). Conclusions Our genomewide association analysis again identified the APOE linkage disequilibrium region as the strongest genetic risk factor for AD. This could be a consequence of the coevolution of more than 1 susceptibility allele, such as APOC1, in this region. We also provide new evidence for additional candidate genetic risk factors for AD that can be tested in further studies.

Journal ArticleDOI
TL;DR: The authors examined the extent to which variation in observed classroom supports (quality of emotional and instructional interactions and amount of exposure to literacy and math activities) predicts trajectories of achievement in reading and math from 54 months to fifth grade.
Abstract: This nonexperimental, longitudinal field study examines the extent to which variation in observed classroom supports (quality of emotional and instructional interactions and amount of exposure to literacy and math activities) predicts trajectories of achievement in reading and math from 54 months to fifth grade. Growth mixture modeling detected two latent classes of readers: fast readers whose skills developed rapidly and leveled off, and a typical group for which reading growth was somewhat less rapid. Only one latent class was identified for math achievement. For reading, there were small positive associations between observed emotional quality of teacher-child interactions and growth. Growth in math achievement showed small positive relations with observed emotional interactions and exposure to math activities. There was a significant interaction between quality and quantity of instruction for reading such that at higher levels of emotional quality there was less of a negative association between amoun...


Journal ArticleDOI
TL;DR: This review addresses what have the authors learned about the effects of EDCs on fish, wildlife, and human health, discusses representative animal studies on (anti)androgens, estrogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals, and evaluates regulatory proposals being considered for screening and testing these chemicals.

Journal ArticleDOI
TL;DR: It is suggested that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND, which are assessed in three independent populations of European origin.
Abstract: Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=69 x 10(-5)) In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=26 x 10(-6)) These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND

Journal ArticleDOI
TL;DR: In this article, the authors examined trends in A1C levels for adults with diagnosed diabetes using three consecutive waves of the National Health and Nutrition Examination Survey (NHANES): 1999-2000, 2001-2002, and 2003-2004.
Abstract: OBJECTIVE —The purpose of this study was to examine whether glycemic control has improved in recent years among individuals with diagnosed diabetes. RESEARCH DESIGN AND METHODS —We examined trends in A1C levels for adults with diagnosed diabetes using three consecutive waves of the National Health and Nutrition Examination Survey (NHANES): 1999–2000, 2001–2002, and 2003–2004. We estimated mean A1C levels and the proportion with A1C RESULTS —Mean A1C levels among individuals with diagnosed diabetes declined from 7.82% in 1999–2000 to 7.47 and 7.18% in 2001–2002 and 2003–2004, respectively. After controlling for demographics and diabetes duration, A1C levels were 0.308 ( P = 0.20) and 0.511 ( P = 0.03) percentage points lower in 2001–2002 and 2003–2004, respectively, than in 1999–2000. The logistic results indicated corresponding improvements over time: the predictive margin for having A1C CONCLUSIONS —Glycemic control improved between 1999 and 2004. This trend may represent an important improvement in diabetes care and is encouraging for future reduction of diabetes-related complications.


Journal ArticleDOI
TL;DR: The findings provide a reference point for future studies on the prevalence and nature of co-occurring conditions in FX; suggest the possibility that certain conditions cluster together; provide evidence that male and female carriers experience elevated rates of co‐occurrence conditions compared with matched groups of non‐carrier children; and emphasize the importance of including an assessment of co­occurring Conditions in any clinical evaluation of individuals with abnormal variation in the FMR1 gene.
Abstract: Parents enrolling in a national survey of families of children with fragile X (FX) reported whether each of their children had been diagnosed or treated for developmental delay or eight conditions frequently associated with FX: attention problems, hyperactivity, aggressiveness, self-injury, autism, seizures, anxiety, or depression. This article reports results for 976 full mutation males, 259 full mutation females, 57 premutation males, and 199 premutation females. Co-occurring conditions were frequently reported for all FMR1 gene variations. The number of co-occurring conditions experienced was strongly associated with parent reports of their child's ability to learn, adaptability, and quality of life. Most individuals with the full mutation experienced multiple co-occurring conditions, with a modal number of 4 for males and 2 for females. Most (>80%) full mutation males and females had been diagnosed or treated for attention problems. Premutation males, when compared with a matched group of non-FX males, were more likely to have been diagnosed or treated for developmental delay, attention problems, aggression, seizures, autism, and anxiety. Premutation females were more likely to have been diagnosed or treated for attention problems, anxiety, depression, and developmental delay. Clusters of conditions were identified, seeming to occur in an additive fashion. Self-injury, autism, and seizures rarely occurred in isolation, but were more likely in individuals who also had problems with attention, anxiety, and hyperactivity. The findings provide a reference point for future studies on the prevalence and nature of co-occurring conditions in FX; suggest the possibility that certain conditions cluster together; provide evidence that male and female carriers experience elevated rates of co-occurring conditions compared with matched groups of non-carrier children; and emphasize the importance of including an assessment of co-occurring conditions in any clinical evaluation of individuals with abnormal variation in the FMR1 gene.

Journal ArticleDOI
TL;DR: Although Affymetrix GeneChip 500K genotype data from 2,514 individuals belonging to 23 different subpopulations was investigated, the existing differences were characterized by a strong continent-wide correlation between geographic and genetic distance, which provided evidence for a spatial continuity of genetic diversity in Europe.

Journal ArticleDOI
TL;DR: The impact of peer weight is larger among females and adolescents with high body mass index and the results are consistent with social multipliers for adolescent overweight policies.

Journal ArticleDOI
TL;DR: It is found that a considerable proportion of transmitted HIV-1 drug resistance is undetected by conventional genotyping and that minority mutations can have clinical consequences, suggesting an important role for sensitive baseline drug resistance testing.
Abstract: Background Transmitted HIV-1 drug resistance can compromise initial antiretroviral therapy (ART); therefore, its detection is important for patient management. The absence of drug-associated selection pressure in treatment-naive persons can cause drug-resistant viruses to decline to levels undetectable by conventional bulk sequencing (minority drug-resistant variants). We used sensitive and simple tests to investigate evidence of transmitted drug resistance in antiretroviral drug-naive persons and assess the clinical implications of minority drug-resistant variants.

Journal ArticleDOI
TL;DR: Although IC ABC HSRs are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for IC ABCHSRs in both US white and black patients suggests similar implications of the association between HLA’s positivity and risk of ABC H SRs inBoth races.
Abstract: Background. Although the human leukocyte antigen (HLA)–B*5701 is highly associated with a hypersensitivity reaction (HSR) to abacavir (ABC), variable sensitivities have been reported when clinical data alone have been used to define an ABC HSR. This study evaluated the sensitivity of detection of the HLA-B*5701 allele as a marker of ABC HSRs in both white and black patients, using skin patch testing to supplement clinical diagnosis. Methods. White and black patients, identified through chart review, were classified as having received a diagnosis of an ABC HSR based on clinical findings only (a clinically suspected ABC HSR) or based on clinical findings and a positive skin patch test result (an immunologically confirmed [IC] ABC HSR). Control subjects were racially matched subjects who tolerated ABC for 12 weeks without experiencing an ABC HSR. Patients and control subjects were tested for the presence of HLA-B*5701. Sensitivity, specificity, and odds ratios for the detection of HLA-B*5701 as a marker for an ABC HSR were calculated for white and black participants. Results. Forty-two (32.3%) of 130 white patients and 5 (7.2%) of 69 black patients who met the criteria for clinically suspected HSRs had IC HSRs. All 42 white patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 1945; 95% confidence interval, 110–34,352). Among all white patients with clinically suspected HSRs, sensitivity was 44% (57 of 130 patients tested positive for HLA-B*5701); specificity among white control subjects was 96%. Five of 5 black patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 900; 95% confidence interval, 38–21,045). Among black patients with clinically suspected HSRs, the sensitivity was 14% (10 of 69 tested positive for HLA-B*5701); specificity among black control subjects was 99%. Conclusions. Although IC ABC HSRs are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for IC ABC HSRs in both US white and black patients suggests similar implications of the association between HLA-B*5701 positivity and risk of ABC HSRs in both races.

Journal ArticleDOI
TL;DR: The thermal challenges in next-generation electronic systems, as identified through panel presentations and ensuing discussions at the workshop, Thermal Challenges in Next Generation Electronic Systems, held in Santa Fe, NM, January 7-10, 2007, are summarized in this article.
Abstract: Thermal challenges in next-generation electronic systems, as identified through panel presentations and ensuing discussions at the workshop, Thermal Challenges in Next Generation Electronic Systems, held in Santa Fe, NM, January 7-10, 2007, are summarized in this paper. Diverse topics are covered, including electrothermal and multiphysics codesign of electronics, new and nanostructured materials, high heat flux thermal management, site-specific thermal management, thermal design of next-generation data centers, thermal challenges for military, automotive, and harsh environment electronic systems, progress and challenges in software tools, and advances in measurement and characterization. Barriers to further progress in each area that require the attention of the research community are identified.

Journal ArticleDOI
TL;DR: A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper, based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally.
Abstract: A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and buffer composition were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776-fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on human insulin and interleukin-6 (IL-6) with a total time to result of 7 min for each assay.

Journal ArticleDOI
TL;DR: A theory of the organizational determinants of effective implementation of comprehensive worksite health promotion programs is described, adapted from theory and research on the implementation of complex innovations in manufacturing, education and health care settings.
Abstract: The field of worksite health promotion has moved toward the development and testing of comprehensive programs that target health behaviors with interventions operating at multiple levels of influence. Yet, observational and process evaluation studies indicate that such programs are challenging for worksites to implement effectively. Research has identified several organizational factors that promote or inhibit effective implementation of comprehensive worksite health promotion programs. However, no integrated theory of implementation has emerged from this research. This article describes a theory of the organizational determinants of effective implementation of comprehensive worksite health promotion programs. The model is adapted from theory and research on the implementation of complex innovations in manufacturing, education and health care settings. The article uses the Working Well Trial to illustrate the model's theoretical constructs. Although the article focuses on comprehensive worksite health promotion programs, the conceptual model may also apply to other types of complex health promotion programs. An organization-level theory of the determinants of effective implementation of worksite health promotion programs.

Journal ArticleDOI
TL;DR: Data indicate that cells present at prospective joint sites and expressing Gdf5 constitute a distinct cohort of progenitor cells responsible for limb joint formation, which appear to be patterned along specific limb symmetry axes and rely on local signaling tools to make distinct contributions to joint formation.

Shelby1
01 Sep 2008
TL;DR: The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans and reached the following conclusions.
Abstract: The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http://cerhr.niehs.nih.gov/). See bisphenol A under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs. nih.gov/chemicals/bisphenol/bisphenol.html). The NTP reached the following conclusions on the possible effects of exposure to bisphenol A on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. The NTP has negligible concern that exposure to bisphenol A will cause reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings. NTP will transmit the NTP-CERHR Monograph on Bisphenol A to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD from CERHR.

Journal ArticleDOI
TL;DR: In this article, the output voltage of the preregulator is always self-adjusted so that the voltage across the linear current regulator of the LED string with the highest voltage drop is kept at the minimum value that is required to maintain the desired string current.
Abstract: This paper presents an LED driver circuit consisting of multiple linear current regulators and a voltage preregulator with adaptive output voltage. In the proposed driver, the output voltage of the preregulator is always self-adjusted so that the voltage across the linear current regulator of the LED string with the highest voltage drop is kept at the minimum value that is required to maintain the desired string current. Because the linear current regulators in this driver operate with the minimum voltages, the driver efficiency is maximized. The performance of the proposed driver was experimentally verified on a four-string LED setup with eight white LEDs in each string. The measured efficiency improvement of the linear current regulators was approximately 15% compared to the corresponding implementation with a constant preregulator voltage.

Journal ArticleDOI
TL;DR: In this article, an approach to infer ground-level nitrogen dioxide (NO2) concentrations by applying local scaling factors from a global three-dimensional model (GEOS-Chem) to tropospheric NO2 columns retrieved from the Ozone Monitoring Instrument (OMI) onboard the Aura satellite is presented.
Abstract: [1] We present an approach to infer ground-level nitrogen dioxide (NO2) concentrations by applying local scaling factors from a global three-dimensional model (GEOS-Chem) to tropospheric NO2 columns retrieved from the Ozone Monitoring Instrument (OMI) onboard the Aura satellite. Seasonal mean OMI surface NO2 derived from the standard tropospheric NO2 data product (Version 1.0.5, Collection 3) varies by more than two orders of magnitude ( 10 ppbv) over North America. Two ground-based data sets are used to validate the surface NO2 estimate and indirectly validate the OMI tropospheric NO2 retrieval: photochemical steady-state (PSS) calculations of NO2 based on in situ NO and O3 measurements, and measurements from a commercial chemiluminescent NO2 analyzer equipped with a molybdenum converter. An interference correction algorithm for the latter is developed using laboratory and field measurements and applied using modeled concentrations of the interfering species. The OMI-derived surface NO2 mixing ratios are compared with an in situ surface NO2 data obtained from the U.S. Environmental Protection Agency's Air Quality System (AQS) and Environment Canada's National Air Pollution Surveillance (NAPS) network for 2005 after correcting for the interference in the in situ data. The overall agreement of the OMI-derived surface NO2 with the corrected in situ measurements and PSS-NO2 is −11–36%. A larger difference in winter/spring than in summer/fall implies a seasonal bias in the OMI NO2 retrieval. The correlation between the OMI-derived surface NO2 and the ground-based measurements is significant (correlation coefficient up to 0.86) with a tendency for higher correlations in polluted areas. The satellite-derived data base of ground level NO2 concentrations could be valuable for assessing exposures of humans and vegetation to NO2, supplementing the capabilities of the ground-based networks, and evaluating air quality models and the effectiveness of air quality control strategies.

Journal ArticleDOI
TL;DR: Dietary bisphenol A was evaluated in a mouse two-generation study and there were no treatment-related effects and no evidence of nonmonotonic dose-response curves for any parameter, therefore, BPA is not considered a selective reproductive or developmental toxicant in mice.