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Prenatal Exposure to PBDEs and Neurodevelopment
[do action="authors"]Julie B. Herbstman,1 Andreas Sjödin,2 Matthew Kurzon,1 Sally A. Lederman,1 Richard S. Jones,2 Virginia Rauh,1 Larry L. Needham,2 Deliang Tang,1 Megan Niedzwiecki,1 Richard Y. Wang,2 Frederica Perera1[/do][do action="affiliations"]1Columbia Center for Children's Environmental Health, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA; 2Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA[/do][do action="citation-string"]Environ Health Perspect 118:712-719 (2010). http://dx.doi.org/10.1289/ehp.0901340 [online 04 January 2010] [/do]
[do action="abstract"]
Background: Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds that are persistent and bioaccumulative and therefore have become ubiquitous environment contaminants. Animal studies suggest that prenatal PBDE exposure may result in adverse neurodevelopmental effects.
Objective: In a longitudinal cohort initiated after 11 September 2001, including 329 mothers who delivered in one of three hospitals in lower Manhattan, New York, we examined prenatal PBDE exposure and neurodevelopment when their children were 12–48 and 72 months of age.
Methods: We analyzed 210 cord blood specimens for selected PBDE congeners and assessed neurodevelopmental effects in the children at 12–48 and 72 months of age; 118, 117, 114, 104, and 96 children with available cord PBDE measurements were assessed at 12, 24, 36, 48, and 72 months, respectively. We used multivariate regression analyses to evaluate the associations between concentrations of individual PBDE congeners and neurodevelopmental indices.
Results: Median cord blood concentrations of PBDE congeners 47, 99, and 100 were 11.2, 3.2, and 1.4 ng/g lipid, respectively. After adjustment for potential confounders, children with higher concentrations of BDEs 47, 99, or 100 scored lower on tests of mental and physical development at 12–48 and 72 months. Associations were significant for 12-month Psychomotor Development Index (BDE-47), 24-month Mental Development Index (MDI) (BDE-47, 99, and 100), 36-month MDI (BDE-100), 48-month full-scale and verbal IQ (BDE-47, 99, and 100) and performance IQ (BDE-100), and 72-month performance IQ (BDE-100).
Conclusions: This epidemiologic study demonstrates neurodevelopmental effects in relation to cord blood PBDE concentrations. Confirmation is needed in other longitudinal studies.
[/do][do action="abstract"]Key words: biomarkers, children, neurodevelopment, PBDEs, polybrominated diphenyl ethers, prenatal, World Trade Center, WTC[/do]
[do action="notes-rule-above"]Address correspondence to J. Herbstman, Columbia Center for Children's Environmental Health, Mailman School of Public Health, 100 Haven Ave. #25F, New York, NY 10032 USA. Telephone: (212) 304-7273. Fax: (212) 544-1943. E-mail: email@example.com[/do][do action="notes"]This research was supported by the September 11th Fund of the New York Community Trust and United Way of New York City; the New York Times 9/11 Neediest Fund; the National Philanthropic Trust; National Institute of Environmental Health Sciences grants ES09089, 5P01 ES09600, and 5R01 ES08977, and U.S. Environmental Protection Agency grant R827027.[/do][do action="notes"]The authors declare they have no actual or potential competing financial interests.[/do][do action="notes"]
We thank C. Dodson, W-J Wang, K. Lester, and L. Stricke.
[/do][do action="notes"] Received 17 August 2009; accepted 04 January 2010; online 04 January 2010.[/do]
[do action="notes"] The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. [/do]
Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds applied to a wide array of textiles, building materials, and electronic equipment, including computers and televisions. Because they are additives rather than chemically bound to consumer products, they have the propensity to be released into the environment (Darnerud et al. 2001). PBDEs are persistent organic chemicals, and some congeners can bioaccumulate; therefore they have become ubiquitous contaminants detectable in the environment, in animals, and in humans (Hites 2004; Sjodin et al. 2008b).
A number of toxicologic studies have demonstrated that exposure to PBDEs may have endocrine-disrupting effects. Most of these studies have focused on thyroid hormone disruption and a smaller number on disruption of the estrogen/androgen hormone system [reviewed by Darnerud (2008)]. Endocrine disruption during critical developmental periods may result in irreversible effects on differentiating tissue, including the brain (Bigsby et al. 1999). Causal relationships between prenatal exposure to PBDEs and indices of developmental neurotoxicity have been observed in experimental animal models [reviewed by Costa and Giordano (2007)]. Thus, the disruption of endocrine pathways by prenatal exposure to hormonally active environmental chemicals may affect neurodevelopment in children.
Although the association between prenatal exposure to PBDEs and adverse neurodevelopmental effects has been observed in animal models, it has not been adequately explored in human populations. In a longitudinal cohort study initiated by the Columbia Center for Children's Environmental Health (CCCEH), we examined the impact of prenatal exposures to selected toxicants, including PBDEs, that may be present in the ambient environment but may also have been emitted from the World Trade Center (WTC) buildings in New York City after the 11 September 2001 (9/11) terrorist attack. Here we report the relationship between prenatal PBDE and polybrominated biphenyl (PBB-153) measured in umbilical cord blood in humans and indicators of neurodevelopment at 12–48 and 72 months of age.
Study population. We established a prospective cohort study of women who were pregnant on 11 September 2001 and subsequently delivered at one of three downtown hospitals including Beth Israel, St. Vincent's (and St. Vincent's affiliated Elizabeth Seton Childbearing Center), which are all approximately 2 miles from the WTC site, and New York University Downtown Hospital, which is within a half-mile of the WTC site. The study methods have been described previously (Lederman et al. 2004). In brief, beginning 12 December 2001 [when institutional review board (IRB) approval was obtained], women were approached in the hospital when they presented for labor and delivery. The women were briefly screened for eligibility, recruited, and enrolled, and they consented before delivery. This study was conducted in accordance with all applicable requirements of the United States (including IRB approval), and all human participants gave written informed consent before participation in this study. Eligible women included those who were between 18 and 39 years of age, reported smoking < 1 cigarette per day during pregnancy, were pregnant on 11 September 2001 (based on their estimated date of conception), and reported no diabetes, hypertension, HIV infection or AIDS, or use of illegal drugs in the preceding year. Not all mothers agreed to have their child followed after birth. For example, some of the Chinese children were to be raised in China [see Supplemental Material, Table 1 (doi:10.1289/ehp.0901340) for follow-up information].
Concentrations (ng/g lipid) of PBDEs and BB-153 in cord blood.
Data collection. Medical records of the mother and newborn were abstracted for information relating to pregnancy, delivery, and birth outcomes. Interviews were conducted (generally the day after delivery) by bilingual interviewers in the preferred or native language (English, Spanish, or Chinese) of the participants. Demographic information, reproductive history, background environmental exposures, occupational history, and the location of the residences and workplaces of the woman during each of the 4 weeks after 11 September 2001 were determined during this interview. Maternal intelligence was measured using the Test of Non-Verbal Intelligence, Second Edition (TONI-2), a 15-min, language-free measure of general intelligence that is relatively stable and free of cultural bias (Brown et al. 1990).
Developmental assessment. When the children were approximately 12, 24, and 36 months of age, the Bayley Scales of Infant Development, Second Edition (BSID-II) were administered, providing scores from the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The BSID-II is a widely used developmental test designed for children 12–42 months of age that is norm-referenced and can be used to identify children with developmental delay. The assessment provides a developmental quotient (raw score/chronological age), generating a continuous MDI or PDI score, both with mean ± SD = 100 ± 15.
When the children were 48 and 72 months of age, the Wechsler Preschool and Primary Scale of Intelligence, Revised Edition (WPPSI-R) was administered, which measures cognitive development and contains verbal and nonverbal performance tests. We used the WPPSI-R because of its availability in Chinese, rather than the third edition.
Not all children were available for all developmental assessments, resulting in different numbers of children tested at each age. Assessments were conducted in the first language of the child (English or Chinese) by trained research technicians. In some cases, when the primary language of the child was not English or Chinese (e.g., Yiddish), we relied on maternal translation. Statistical analyses for this study were conducted with and without the children for whom the child's primary language was not English or Chinese (n = 30), and the results were similar (data not shown).
Most assessments were conducted at the CCCEH. However, a proportion of the assessments were conducted in the child's home if the parents were unable or unwilling to come to the center to complete the follow-up [see Supplemental Material, Table 1 (doi:10.1289/ehp.0901340) for details].
Blood collection. Umbilical cord blood was collected at delivery, and maternal blood was typically collected on the day after delivery. On average, 30.7 mL blood was collected from the umbilical cord, and 30–35 mL blood was collected from the mothers. Samples were transported to the laboratory and processed within several hours of collection. The buffy coat, packed red blood cells, and plasma were separated and stored at –70°C. Frozen plasma from 210 cord samples was transferred on dry ice to the Centers for Disease Control and Prevention for laboratory analyses for the PBDEs and PBB-153. The concentrations of these chemicals in the cord blood were used as an indicator of fetal exposure during gestation (Mazdai et al. 2003; Qiu et al. 2009).
Laboratory methods. Details regarding the analysis of the plasma samples for PBDEs are given elsewhere (Hovander et al. 2000; Sjodin et al. 2004). Briefly, the samples were automatically fortified with 13C-labeled internal standards. The samples were subjected to an initial liquid/liquid extraction with hexane:methyl-tert-butyl ether after denaturation with 1 M HCl and isopropanol (Hovander et al. 2000). Thereafter, coextracted lipids were removed on a silica:silica/sulfuric acid column using the Rapid Trace equipment (Zymark, Hopkinton, MA) for automation. Final determination of the target analytes was performed by gas chromatography-isotope dilution high-resolution mass spectrometry employing an MAT95XP (ThermoFinnigan MAT, Bremen, Germany) instrument (Sjodin et al. 2004). Concentrations of target analytes were reported as picograms per gram whole weight (weight of plasma) and nanograms per gram lipid weight (weight of plasma lipids). The plasma lipid concentrations were determined using commercially available test kits from Roche Diagnostics Corp. (Indianapolis, IN) for the quantitative determination of total triglycerides (product no. 011002803-0600) and total cholesterol (product no. 011573303-0600). Final determinations were made on a Hitachi 912 Chemistry Analyzer (Hitachi, Tokyo, Japan). Limits of quantification were determined in relation to the method blanks and in relation to the quantification limit of the instrument, which is proportional to the sample size. Cotinine concentrations were measured in cord and maternal blood by use of liquid chromatography in conjunction with atmospheric pressure ionization tandem mass spectrometry (Bernert et al. 1997).
The plasma samples were analyzed for the following PBDE congeners (by International Union of Pure and Applied Chemistry numbers): 2,2,2´,4,4´-tetraBDE (BDE-47); 2,2´,3,4,4´-pentaBDE (BDE-85); 2,2´,4,4´,5-pentaBDE (BDE-99); 2,2´,4,4´,6-pentaBDE (BDE-100); 2,2´,4,4´,5,5´-hexaBDE (BDE-153); 2,2´,4,4´,5,6´-hexaBDE (BDE-154); 2,2´,3,4,4´,5´,6-heptaBDE (BDE-183); and 2,2´,4,4´,5,5´-hexaBB (BB-153).
Quality control/quality assurance. We determined background levels by measuring the level of target analytes in blank samples in the same run as the study samples (three blanks per 24 study samples). All concentrations reported were corrected for the average amount present in the blank samples. The limit of detection (LOD) when no analytical background was detected in blank samples was defined as a signal-to-noise ratio > 3. When an analytical background was detected in the blanks, the LOD was defined as three times the SD of the blanks.
The plasma samples used in this cohort were not collected solely for the purpose of PBDE analysis. Therefore, we examined the ratio of BDE-99 over BDE-47 for any indication of contamination from indoor particulate matter, with the assumption that a high ratio would indicate sample contamination during sample collection. The median ratio of BDE-99 over BDE-47 is 1.2 in residential dust samples (Sjodin et al. 2008a), whereas in human samples this ratio is typically significantly lower. In the 2003–2004 National Health and Nutrition Examination Survey (NHANES), the median ratio of BDE-99 to BDE-47 was 0.23, whereas the 95th percentile of this ratio was 0.43 (Sjodin et al. 2008b). In our study, we found that 16 of 210 samples had a BDE-99 to BDE-47 ratio > 0.43, corresponding to 7.6% of the samples. This frequency of samples having a ratio > 0.43 is similar to that of the NHANES survey, and we can thus conclude that no detectable contamination occurred during the collection of the cord samples in this study. Statistical analyses for this study were conducted both including and excluding the aberrant samples (n = 16), and the results were similar (data not shown).
WTC exposure. In previous analyses in this cohort, we used two indices to describe exposure to the WTC: geographic proximity to the WTC during the first month after 9/11 and timing of exposure relative to date of delivery. We found that women who lived closest to the WTC during the first month after 9/11 (constituting the group we would estimate to have the largest exposure to the WTC) did not have higher concentrations of PBDEs compared with those who lived farther from the towers in the first 4 weeks after the attack. However, we found that women who delivered sooner after 9/11 (constituting the group who were further along in their pregnancy on 9/11) tended to have higher cord blood concentrations of PBDEs (unpublished data). Because we quantify prenatal PBDE exposure using a biological marker that integrates exposure from all sources, the source of the PBDEs is not relevant to the effect of prenatal exposure to PBDEs on neurodevelopment. To our knowledge, PBDEs are not associated with any other neurotoxic exposure that could confound the observed associations.
Statistical methods. Concentrations of PBDEs were lipid- and natural log-adjusted. PBDEs commonly detected in cord blood (detected in > 55% of samples) were handled as continuous variables in the statistical models. This was the case for BDEs 47, 99, 100, and 153. We used the LOD divided by the square root of 2 for concentrations below the LOD. Based on the log-normal distribution of each of these BDE congeners, we also compared participants having cord concentrations in the highest 20% with those in the lowest 80% of the population distribution to evaluate the impact of having exposures at the high end of the exposure distribution. This categorization was selected because it distinguished those with exposures in the tail of the log-normal distribution. The majority of cord samples (> 50%) had levels below the limits of detection for BDEs 85, 154, and 183, and BB-153. We evaluated BDE-85 and BB-153 as dichotomous measures (detected vs. nondetected); we did not analyze BDEs 154 and 183 because only 6% and 4% of the samples, respectively, had detectable concentrations (Table 1).
We generated descriptive statistics and evaluated bivariate associations using analysis of variance and chi-square tests to compare stratum-specific means and proportions, respectively. We examined the data using lowess curves and determined that linear models using natural logarithmic (ln)-transformed PBDE concentrations fit the data well. Therefore, we conducted multivariate linear regression analyses to evaluate the relationships between prenatal PBDE concentrations (using continuous measures for ln-transformed BDEs 47, 99, 100, and 153 and dichotomous measures for BDEs 85, 154, and 183) and continuous scores on developmental tests (MDI and PDI at 12, 24, and 36 months and Full, Verbal, and Performance scores at 48 and 72 months). We were not able to consider developmental test scores as dichotomous measures, using the test-specific recommended cutoffs for defining children as "delayed" or "borderline delayed" because of the small sample size and small number of children who met these criteria.
We selected covariates for inclusion in multivariate models based on their a priori association with neurodevelopment (Tong and Lu 2001), including age at testing, sex of child, ethnicity (Asian, black, white, or other), environmental tobacco smoke (ETS) exposure in the home [yes/no; based on self-report and validated in this data set by cotinine measured in cord blood, using methodology described by Jedrychowski et al. (2009)] and IQ of the mother. We also considered the inclusion of additional covariates if they changed the beta coefficient for PBDEs > 10% when they were added to the a priori set one at a time. This resulted in a final covariate set that added to our a priori set gestational age at birth (based on the best obstetric estimate), maternal age, maternal education, material hardship during pregnancy (defined as having gone without either food, shelter, gas/electric, clothing, or medication/medical care because of financial constraint), and breast-feeding [considering both breast-feeding duration and exclusiveness, defined by Lederman et al. (2008)]. The results of these models are presented as model 1. We also created a model 2, which included all the previous covariates plus two study-specific variables: the language (including whether the mother aided in translation) and location (home or study site) of the interview and assessment. We explored the effects of whether the mother ate fish/seafood when she was pregnant (yes/no) and also the effects of cord blood total mercury and lead concentrations (continuous measures), but found that these covariates did not materially change the relationships between PBDE concentrations and developmental indicators.
To determine whether only a few cases could have a substantial association with the adjusted PBDE regression coefficients, we used AV plots to examine the residuals from the regression lines for the adjusted PBDE regression coefficients to find possible influential cases. These are cases that are outliers both for the outcomes (PDI, MDI, WPPSI) and the independent variables of interest (PBDE compounds). When the possible influential cases were removed, the largest changes in the regression coefficients were < 1 point, with no changes in significance levels, using p < 0.05 as a cut point.
Median cord concentrations of PBDE congeners 47, 99, and 100 in the full cohort were 11.2, 3.2, and 1.4 ng/g lipid; 81.4%, 59.5%, and 63.6%, respectively, were above the LOD (Table 1). Overall concentrations and the proportion of participants with PBDE concentrations above the LOD were not significantly different in the study subsample. The proportion of participants with detectable concentrations of BDEs 85, 153, 154, and 183 ranged from approximately 4% to 50%. PBDE congeners 47, 99, and 100 were highly intercorrelated (r = 0.74–0.88).
Characteristics of the full cohort (n = 329), the subset of 210 participants with cord PBDE (and PBB) measurements, and the subset of 152 with both cord measurement and a neurodevelopmental test are shown in Table 2. Those with cord blood measurements were similar to the full cohort except that there were proportionally more Chinese participants with cord blood measurements (34.3% compared with 28.0% in the full cohort) and those with measurements were slightly smaller in birth length. The study sample and the full cohort were similar except that mothers included in the study sample were slightly older at the time of delivery (31.2 vs. 30.2 years, p < 0.01) and were more educated (not statistically significant). Those in the study sample were more likely to have completed maternal IQ measurements, which is expected, considering that this measurement was collected at follow-up visits, not at the delivery hospital. There were no differences in the proportions working and/or living closest to the WTC (within 1 or 2 miles) at the time of the attack.
Characteristics of all cohort members (n = 329), participants with cord blood measurement of PBDEs (n = 210), and those included in our study sample (n = 152).
There were 118, 117, 114, 104, and 96 children with available cord PBDE measurements who also had a developmental assessment at 12, 24, 36, 48, and 72 months of age, respectively. For those assessed at all of these time points, the median cord plasma concentrations of BDE-47 and 99 were 12.1 ng/g lipid and 3.5 ng/g lipid. For BDE-100, median concentrations were approximately 1.5 ng/g lipid for children assessed at 12–48 months; for those assessed at 72 months, the median cord blood concentration was 1.4 ng/lipid.
In cross-sectional analyses using multivariate linear regression, prenatal exposure to BDE-47 was negatively associated with neurodevelopmental indices (Table 3). These relationships were statistically significant for 12-month PDI (borderline), 24-month MDI, and 48-month Full and Verbal IQ scores. For every ln-unit change in BDE-47, scores were, on average, 2.1–3.1 points lower on developmental indices. For BDE-99 (Table 4), statistically significant negative associations were detected for 24-month MDI [β = –2.82; 95% confidence interval (CI), –4.86 to –0.78]. Prenatal exposure to BDE-100 was negatively associated with neurodevelopmental indices (Table 5), with statistically significant relationships observed for 24-month MDI, 48-month Full, Verbal, and Performance IQ scores, and 72-month Performance IQ scores. For every ln-unit change in BDE-100, scores were, on average, 3.4–4.0 points lower on developmental indices. For BDE-153 (Table 6), statistically significant negative associations were detected for 48-month and 72-month Full and Performance IQ scores. For every ln-unit change in BDE-153, scores were, on average, 3.1–4.2 points lower. The strength of association between BDE-153 and IQ scores was much larger in the adjusted models compared with the univariate model. It appears that the strong positive association of maternal education between IQs at ages 48 and 72 months was responsible for much of this change.
Association (95% CIs) between prenatal exposure to BDE‑47 and indices of neurodevelopment at 12, 24, 36, 48, and 72 months of age.
Association (95% CIs) between prenatal exposure to BDE‑99 and indices of neurodevelopment at 12, 24, 36, 48, and 72 months of age.
Association (95% CIs) between prenatal exposure to BDE‑100 and indices of neurodevelopment at 12, 24, 36, 48, and 72 months of age.
Association (95% CIs) between prenatal exposure to BDE‑153 and indices of neurodevelopment at 12, 24, 36, 48, and 72 months of age.
We also evaluated the difference in mean developmental score comparing children who were in the highest 20% of the prenatal exposure distribution with those in the lower 80% of the distribution for BDEs 47, 99, and 100 (Figure 1). We found that, on average, children with the higher prenatal concentrations of BDEs 47, 99, and 100 scored lower than the rest of the population on nearly all neurodevelopmental indices at all time points (12–48 and 72 months). These differences ranged in magnitude; the largest differences were observed with all three congeners for the 24-month MDI (statistically significant differences of –7.7, –9.3, and –10.9 points for BDEs 47, 99, and 100, respectively) and for 48-month Verbal and Full IQ scores (ranging from –5.5 to –8.0 points). For BDE-153, adjusting for the same covariate set, those in the highest 20% of the exposure distribution scored, on average, 6.3 points lower at 48 months (95% CI, –13.0 to 0.4) and 8.1 points lower at 72 months (95% CI, –15.6 to –0.6) on the performance IQ scale.
Difference in mean developmental score (and 95% confidence interval around the mean) comparing individuals in the highest quintile (20%) of exposure with those in the lower 80% of BDEs 47, 99, and 100. Mean differences were adjusted for age at testing, race/ethnicity, IQ of mother, sex of child, gestational age at birth, maternal age, ETS (yes/no), maternal education, material hardship, breast-feeding, language, and location of interview.
We used multivariate linear regression models to evaluate whether having detectable prenatal concentrations of BDE-85 and BB-153 was significantly related to developmental indices. Adjusting for the exact age of the child at test administration, ethnicity, IQ of the mother, sex of the child, gestational age at birth, maternal age, ETS (yes/no), maternal education, material hardship, and breast-feeding, we found that those with detectable cord concentrations of BDE-85 scored, on average, 11 points lower on the 24-month MDI (95% CI, –17.0 to –5.2); 6.4 points lower on 24-month PDI (95% CI, –11.8 to –0.8); 7.7 points lower on 36-month PDI (95% CI, –15.0 to –0.4); 6.5 points lower on 48-month Verbal IQ (95% CI, –13.3 to 0.2); and 6.9 points lower on 48-month Full IQ (95% CI, –12.8 to –0.9). There were no statistically significant associations between prenatal BB-153 levels with developmental indices measured at any other ages.
We found evidence suggesting that children who had higher cord blood concentrations of BDEs 47, 99, and 100 scored lower on tests of mental and physical development at ages 12–48 and 72 months. These associations were significant for 12-month PDI (BDE-47); 24-month MDI (BDEs 47, 99, and 100); 48-month Full IQ (BDEs 47, 100, and 153); Verbal IQ (BDEs 47 and 100) and Performance IQ (BDEs 100 and 153); and 72-month full and Performance IQ (BDEs 100 and 153). Children who were in the highest 20% of cord blood concentrations of BDEs 47, 99, or 100 had significantly lower developmental scores compared with children who were in the lower 80% of the exposure distributions for these chemicals. These differences were particularly evident at 48 months of age.
Adverse neurodevelopmental effects associated with prenatal PBDE exposure can be detected both at early ages (12–36 months) and as the children age (48 and 72 months). Neurodevelopmental deficits documented by the WPPSI during the preschool period are an important predictor of subsequent academic performance (Kaplan 1993). Documenting the first appearance of potentially longer-term adverse effects at early ages is also important, because these indicators may identify children who could benefit from early intervention programs. The identification of later deficits may indicate the persistence of early effects and/or an increase in the magnitude of effect with age, as has been shown in some animal studies (e.g., Viberg et al. 2003a).
Our results are consistent across congeners and over time. This may be predictable because the PBDE congeners are highly correlated, and for individuals, repeated developmental scores are also correlated. Although the number of participants lost to follow-up between 12 and 72 months was relatively low (81% of subjects available for analyses at 12 months were also assessed at 72 months) and losses are independent of exposure, our overall sample is relatively small. Therefore, even small losses to follow-up may limit our power to detect significant differences in multivariate models. The resulting small sample size precluded the analysis of exposure effects on developmental delay, and we were unable to look at interactions. However, the developmental deficits of the magnitude we observed in this study are likely to have the largest functional impact on those who score at the lower end of the population distribution.
The only other epidemiologic study reporting the neurodevelopmental effects of prenatal exposure to PBDEs was published recently (Roze et al. 2009). In this study of 62 Dutch children, the authors present correlations between exposure to PBDEs (measured during the 35th week of pregnancy) and > 20 indices of child development and behavior at age 60–72 months. The authors report that prenatal PBDE exposure was associated with some adverse effects on development (reduced fine manipulative abilities and increased attentional deficits) as well as some beneficial effects (better coordination, better visual perception, and better behavior). The authors evaluated, but did not find statistically significant, correlations between prenatal PBDE exposures and any of the WPPSI-R domains. Our results are not consistent with these findings. However, important differences in exposure (median exposure in our population was 4 times higher for BDEs 47 and 99; 2.3 times higher for BDE-100; and one-fifth their concentration for BDE-153), sample size, and statistical analyses performed may account for some of the observed inconsistencies.
Our results are consistent with published toxicologic experiments [reviewed by Costa and Giordano (2007)]. For example, studies evaluating the neurodevelopmental effects of neonatal exposure to PBDEs in mice during critical developmental periods have reported altered habituation patterns (Viberg et al. 2003a, 2003b), hyperactivity (Gee and Moser 2008), and learning and memory deficits (Dufault et al. 2005; Viberg et al. 2003a). There is some evidence suggesting that BDE-99 is more potent than BDE-47 (Viberg et al. 2003a) and also that effects worsen (or are more apparent) with age (Viberg et al. 2003a). In general, we observed the largest associations with prenatal exposure to BDE-100, and the associations with prenatal exposures were still apparent, albeit not consistently significant, in our smaller sample examined at 72 months of age.
A number of potential mechanisms have been proposed to explain the cognitive and locomotive deficits observed in animals after PBDE exposure during critical developmental periods, including direct neurotoxic effects on neuronal and glial cells (Costa et al. 2008) resulting from changes in the quantity of cholinergic nicotinic receptors in the hippocampus (Viberg et al. 2003a) and induction of apoptotic cerebellar granule cell death (Reistad et al. 2006). In addition, there is compelling experimental and epidemiologic evidence suggesting that PBDEs can interfere with thyroid hormone pathways (Legler 2008). Because thyroid hormones are critical for normal brain development, this provides an attractive explanation for observed neurodevelopmental effects after neonatal PBDE exposure (Bigsby et al. 1999; Porterfield 2000). Toxicologic evidence corroborating this theory includes potentially causal associations between neonatal exposure to BDE-47, BDE-99, or commercial PBDE mixtures (DE-71 and Bromokal 70-5 DE) and reduced thyroxine (T4) concentrations in experimental murine models (Fowles et al. 1994; Hallgren et al. 2001; Kuriyama et al. 2007).
Although only limited human epidemiologic data are available, increased levels of BDEs 47, 99, and 100 in dust in the homes of adult human males recruited through a U.S. infertility clinic were associated with altered hormone levels. PBDEs were inversely associated with free androgen index and with luteinizing and follicle-stimulating hormones and were positively associated with inhibin B, sex hormone–binding globulin, and free T4 (Meeker et al. 2009). In another study of adult males, increased serum concentrations of PBDEs were positively related to T4 and inversely related to total triiodothyronine (T3) and thyroid-stimulating hormone (TSH) (Turyk et al. 2008). The positive associations between PBDEs and T4 levels demonstrated in these human studies are not consistent with the results from experimental animal models, raising the possibility that the underlying mechanism of the effect of PBDEs on thyroid disruption may differ among species. However, it is difficult to extrapolate findings from studies evaluating exposure effects in adults to prenatal exposures, because PBDEs may exhibit differential effects on thyroid hormone levels at different stages of the life span. A recent study of PBDEs measured in human cord blood of infants born to a cross-section of women delivering in Baltimore, Maryland, showed a consistent nonsignificant negative association with both total and free T4 in infants (Herbstman et al. 2008). More research is necessary to fully characterize the association of human prenatal exposure to PBDEs with thyroid hormone levels.
The exact mechanism of thyroid disruption by PBDEs in humans has not yet been elucidated, but two potential pathways through which PBDE exposure could lead to thyroid disruption have been proposed [reviewed by Zhang et al. (2008)]. The structural similarities of T4 and T3 to polyhalogenated aromatic hydrocarbons suggest that hydroxylated PBDE metabolites could displace thyroid hormones from thyroid transport proteins (i.e., transthyretin), altering free thyroid hormone levels (Turyk et al. 2008). Alternatively (or in addition), PBDEs might affect hormone levels by influencing thyroid hormone synthesis and/or stimulating thyroid hormone metabolism (Szabo et al. 2009; Turyk et al. 2008). Brain development in the fetus is contingent on the precise timing of thyroid hormone levels, particularly for T4, and deviations above or below the normal levels can lead to developmental deficits (Williams 2008). The fetus originally derives all thyroid hormone from the mother, but over the course of the pregnancy, its thyroid gland develops, and hormones produced within the fetus gradually replace the maternal source. The surge in maternal T4 in the first trimester, coupled with TSH inhibition, is thought to provide a supply of hormone during this critical developmental period, and alteration of T4 levels by PBDEs at this time could alter neurodevelopment (Williams 2008). Although low serum T4 from maternal hypothyroidism during gestation (e.g., iodine deficiency) is known to cause mental retardation in children, elevated levels of T4 have been associated with increased rates of miscarriage (Anselmo et al. 2004) and could potentially be linked to neurodevelopmental problems.
Because of their similar chemical structures, PBDEs and polychlorinated biphenyls (PCBs) have been compared in terms of their potential health effects. Although PCBs were banned in most industrialized countries > 25 years ago, they are still measurable in human and environmental samples because of their long half-lives in the environment and in humans (Talsness 2008). Prenatal exposure to PCBs has been shown in several cohort studies to significantly reduce cognitive function during childhood [reviewed by Schantz et al. (2003)] and has also been associated in some studies with altered thyroid hormone levels (Chevrier et al. 2007; Herbstman et al. 2008). Because of the structural similarity of PCBs and PBDEs, it has been postulated that they exert biological effects through similar processes.
This study population is unique in that participants were initially recruited to measure the extent and the effects of prenatal exposure to contaminants (including PBDEs) that were potentially released by the destruction of the WTC towers. Studies examining environmental samples collected pre- and post-9/11 near the WTC site found indications of higher concentrations of PBDEs after the attacks (Litten et al. 2003) and nearer to the WTC disaster site (Butt et al. 2004). These trends may be attributable to debris containing office equipment known to be treated with PBDEs (de Wit 2002). In our study population, cord plasma levels of PBDEs were not significantly related to residential distance from the WTC site. There is some evidence suggesting that PBDE exposure may be related to the WTC attack based on the gestational age on 9/11, such that women who were in the second half of their pregnancy on 9/11 had children with higher cord concentrations of PBDEs (unpublished data). It is also possible that just after 9/11, some women had elevated levels of PBDEs but that these levels declined with the passage of time between the peak exposure and delivery, resulting in lower observed levels. In either scenario, it is not clear how much this apparent association between gestational age on 9/11 and exposure concentration contributes to the body burden, and it is certain that sources other than the WTC are also accountable. In this report, our interest is in the association between the integrated prenatal PBDE exposure from multiple sources and neurodevelopment. It is also possible that there are other unknown factors associated with PBDEs that may confound the observed relationships between prenatal PBDE exposure and adverse neurodevelopment.
Levels of cord blood PBDEs in our population are consistent with those reported in other U.S. populations (Herbstman et al. 2007; Mazdai et al. 2003; Wu et al. 2007). Compared with cord blood measurements in an inner-city population in Baltimore, Maryland, our study population had slightly lower median concentrations (i.e., 11.2 ng/g lipid vs. 13.6 ng/g lipid for BDE-47) (Herbstman et al. 2007). In the Baltimore cohort as well as in this New York City cohort, higher cord PBDE concentrations were associated with mothers' African American or non-Asian race/ethnicity, although a higher proportion of the Baltimore population was African American (70% vs. 15%) and a lower proportion was Asian (8% vs. 30%). Increasing maternal age was associated with lower PBDE concentrations in the Baltimore cohort but not in New York City; however the median maternal age was also lower in Baltimore (25 years vs. 30 years) (Herbstman et al. 2007). The demographic differences between these two populations may explain the small differences in blood levels observed at the population level.
Although dietary ingestion was once thought to be the largest route of PBDE exposure in humans, the similarity of PBDE levels in foods in Europe, Asia, and North America fails to adequately explain the high blood levels in the U.S. population (Frederiksen et al. 2009). Dust inhalation may be a more important exposure route to PBDEs, particularly BDEs 47, 99, and 100. In a review of median PBDE levels in dust and air samples, measured BDE-47 dust levels in Europe and North America were 32 and 429 ng/g of dust, respectively. Similar disparities were observed for BDE-99 and BDE-100 levels (Frederiksen et al. 2009; Sjodin et al. 2008a). Particular attention should be given to this exposure route in young children, who are more likely to encounter dust because of their proximity to the floor. Dust is estimated to contribute from 80 to 93% of PBDE exposure in toddlers, and their small body size compounds the effect of their exposures (Costa and Giordano 2007). In this study, we were not able to control for postnatal dust exposure.
In the general population, infants and toddlers have the highest body burden of PBDEs, and along with dust exposure, exposure via breast milk is thought to be a major contributor to this burden (Costa et al. 2008; Toms et al. 2009). Breast-fed infants are estimated to be exposed to 306 ng/kg body weight/day PDBE compared with 1 ng/kg body weight/day in adults, with the most prominent congeners being BDEs 47, 99, and 153 (Costa et al. 2008). In our study, breast-feeding rates were higher in children with higher cord PBDE levels, indicating that PBDEs measured in cord blood may underestimate the exposure of breast-fed children. Breast-feeding was, as expected, associated with higher scores on neurodevelopmental indices, making it an important potential confounder to include in multivariate statistical models.
This report is among the first epidemiologic studies to demonstrate inverse associations between elevated cord blood concentrations of PBDEs and adverse neurodevelopmental test scores. These findings indicate a need for additional work to advance our understanding of the effects of perinatal exposure to PBDEs on neurodevelopment and to evaluate the role of thyroid hormones in this process. Additional PBDE congeners not measured in our study should also be examined to determine whether other congeners, including those that are highly brominated, play a role in developmental outcomes. Future work should also explore the possibility of interactions of PBDEs with other chemicals such as PCBs and dichlorodiphenyldichloroethylene. Although additional studies exploring the associations between PBDE exposure and developmental effects are underway, the identification of opportunities to reduce exposure to these compounds should be a priority.
Attached Files
Related EHP Articles
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- Gee JR, Moser VC. 2008. Acute postnatal exposure to brominated diphenylether 47 delays neuromotor ontogeny and alters motor activity in mice. Neurotoxicol Teratol 30(2):79–87.
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ST. LOUIS (AP) - Protests over the fatal police shooting of 18-year-old Michael Brown have migrated to the city of St. Louis as demonstrators continue to press for broader reforms to local and federal law enforcement.
About 100 protesters marched Tuesday from St. Louis City Hall to the downtown federal courthouse several blocks away. They were calling attention not only to Brown's death but also the fatal shooting of 25-year-old Kajieme Powell by St. Louis police 10 days later.
The demonstrators want amnesty for protesters arrested by St. Louis police since Brown's Aug. 9 shooting by Ferguson officer Darren Brown. The St. Louis police force is among many local departments summoned for crowd control.
Protesters also called for creation of a civilian review board to monitor St. Louis police shootings and other uses of force.
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subset: commoncrawl


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Entertainment of Monday, 12 November 2012
Source: GhanaWeb
Ghana's King of rhythm and blues after a successful premiere of his "Number 1" single which was on various charts around the world continues to show a massive comeback with release of others singles.
He has been on numerous platforms this year including Ghana MT Naija, Keri Hilson Concert, RnB Rave and a lot more.
One of the songs that his making serious waves this year is Chemphe's "Number 1" single which has led to numerous award nominations this year. One of the recent nominations was the 4syte music video awards which he bagged two nominations for best edited and Best male video.
Critics have given very good remarks about the video and are poised to win both accolades.
The Europe GMAs is no exception to Chemphe's numerous nominations. The recent release of the nomination list indicated Chemphe being nominated for Best Male Artiste category.
The event will be held in London (UK) this month and will be a very interesting night seeing the Ghanaians in the diaspora, being recognized at GMA on their offshore home soil.
Chemphe is however set to release his "Left Over" video this month and is also impressed with the support from the national populace for his anti-poverty project.


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When Wendy (right) was self diagnosed with a gluten intolerance in 2006, she immediately felt relief from a life of digestive issues. But a new issue arose, her food choices lacked flavor and texture and her choices of what to eat became limited. Wendy began her journey into the world of gluten free cooking and baking. After many years of self study, she decided to take an immersion course at the acclaimed Culinary Institute of America and began trying recipes out on unsuspecting friends. Soon friends and family began asking for treats for their parties, and they were not even gluten intolerant. Wendy knew her fresh baked goods were ready for the public.
So, Wendy and Letha (left) decided to take the plunge and open their own bakery. Bake Me Happy is committed to making your next bite the most decadent thing you have tried since sliced bread. Satisfy your next craving with a baked good that won't crumble to dust and leave you feeling like there is no pleasure in food. Wendy is a part of the community she serves, understanding the importance of what she does, and also knows that you cannot rush a perfect recipe.
Bake Me Happy is a wholesale, gluten free bakery. We're often asked how we got started in the gluten-free business. The short answer is that within our own family we discovered an intolerance to gluten that necessitated a change in diet. The broader answer is that, because we personally know how it feels to require a not-quite-mainstream diet, we're committed to making it easier for other gluten-free folks to enjoy delicious food that doesn't separate them from their gluten-full friends and family. For us, it's not enough to make a passable gluten-free substitute; we'd rather create something that everyone in the house, office or restaurant, or at the party will enjoy. We love spreading the love, and we'll always go the extra mile to bring people together and make them feel special. Why? Because we get responses like these:
"Better than ANY gluten-filled cookie."
"I am a devoted customer for life."
"Better than the original."
"Best Peanut Butter Cookie. Ever."
Bake Me Happy will use this loan to acquire assistance with marketing and PR. The loan will assist us with updating our website as well as developing increased media presence and press releases. We believe that we are gaining momentum in the Columbus, Ohio area, but we need to increase our marketing for brand recognition. Bake Me Happy will benefit from the investment in marketing through increased sales in the retail as well as wholesale market.


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Asked by:
Win2k8 Server Disk Defragmenter
The versions of Disk Defragmenter in Win2k3, Win2k and WinXP provide a report indicating what files are defragmented and the extent of that fragmentation. The version in Vista and Win2k8 do not appear to have this anymore. Is this something that was taken out, or is there some setting I am missing? Quite honestly, I would really like to know what I am getting myself in for, if I need to run this on a database server.
Greg Wilkerson
All replies
Hi Greg,
Advanced users can use the command line tool Defrag.exe to generate detailed reports and perform other advanced tasks.
For more information about Defrag.exe, please refer to the following articles:
Running Disk Defragmenter from Command Prompt
Get Detailed Statistics By Running Windows Vista Disk Defragmenter From The Command Prompt
Hope it helps.
Tim Quan - MSFT
- Marked as answer by Tim QuanModerator Friday, November 07, 2008 2:54 AM
- Unmarked as answer by Greg Wilkerson Friday, November 07, 2008 12:50 PM
- Marked as answer by Tim QuanModerator Monday, November 10, 2008 8:38 AM
- Unmarked as answer by Greg Wilkerson Monday, November 10, 2008 2:09 PM
Thanks Tim,
But, that really doesn't help at all. Ultimately, I need to know how many fragments are present in my database files. The comment about "file fragments larger that 64MB" concerns me, too. Database file fragments are almost always greater than 64MB is size, many in the GB range. Defragmenting a database file system is a time consuming, performance degrading process and must be a planned and coordinated event. So, knowing the fragmentation status of the database files is important.
I guess the -w and -a options are mutually exclusive. I hoped that using that option would address fragments > 64MB. No joy!
Will the older defrag utility run on w2k8/vista? I'll try it on my Vista machine.
Thanks again,
Hi, Greg
Why do you need to know how many fragments are present in your database files? What are you trying to accomplish?
I'm asking because maybe there is an alternative way, if we know why you need to know the number of fragments...
many thanks
Malu Menezes
Messages in this forum are provided "AS IS" with no warranties
Storage Team at Microsoft
Hi Malu,
What I am trying to accomplish is to actively manage the database file fragmentation that results from either planned or unplanned data file growths. A file defragmentation for database files is not something that I care to set up to run automatically. The defrag process is very disk intensive and database response plummets when those run. I typically have to schedule a maintenance window when defrags are necessary. With the database file fragments typically being GBs in size, the amount of time required to complete the defrag can be extensive. A defrag is not necessary if the file only has a few, I don't know, say 5 fragments. But, if it has 10 or 20 or 50, I do need to defrag it. That is where the reporting of the old defrag utility was valuable. Part of being a DBA is actively managing potential performance issues. This is one of those.
Also, can you address the comment from the defrag utility about fragment > 64MB. In virtually all cases, the database file fragments are going to be larger the 64MB.
Please refer me to the appropriate technical articles if my thoughts are misguided or if SQL Server 2005 and 2008 is somehow less sensitive to database file fragmentation.
For the Microsoft guys that are listening, are the any updates to this? Is there a reason I should not care? Is there a reason why I should just trust the defragger to run on its own and be assured that when it does decide to run, it will not bring my database response to a crawl? Is there a reason why the reporting capability was removed?
I'm just looking for some answers.
Greg Wilkerson
I am listening, and while I am ex Microsoftee, what I am saying here does not represent any official Microsoft position
The line of thought is that defragging runs/fragments/pieces of files that are > 64MB in length provides very limited benefits. Assume that you have a database file stored as 64MB, SomeOtherFile1, 64MB, etc. If the database is being read/written in say 4kb chunks, you will get quite a few reads/writes done sequentially with the first 64MB run, then need some disk head repositioning, then do quite a few read/writes without disk head repositioning. Avoding this one disk head repositioning can cause quite some I/O and possibly some application downtime if the I/O is deemed too disruptive
I dont think SQL 2005/2008 are any less sensitive
Does this help?
Hi Dilip,
Interesting line of thought. I can see that point, to a point. I do have concerns about database files that may have a LOT of fragments. Especially large databases used for reporting where processes execute 100's of thousands of reads. To appease those concerns, I will have to put some numbers together. But, as the current tool is implemented I still have no way of knowing and that is disturbing. Why hide the fragment data? What possible advantage is provided to the customer by removing this? Now I, and my customers, have less information available to make intelligent decisions from.
Greg Wilkerson
You need to defragment INSIDE SQL server databases not use an external version.
Twilliamsen, I believe you're talking about database fragmentation of indexes etc. Greg is talking about File System fragmentation. I'm facing the same problem taking over some SQL servers where the DB's were set to default growth size AND autoshrink.. :----(
Greg, i'm using Contig.exe from Sysinternals now and so far so good. I agree that MS made a horrible decision to get rid of the details in the Defragmenter. With the new Windows system, it seems like the trend it to hide EVERYTHING.. menus, options, etc. Admins like to see what's going on, we like reports, graphs, etc. I hate when they decide for me what is important or not, whether i'm right or wrong.
Have you found a tool or a solution?
I'm considering alternatives such as a restore or copy of the files to a contiguous block on the disk... This may seem pointless now with the contig.exe as i can defrag the individual files. But the thought of "transplanting" the file to an "open space" seems attractive :)
I actually like your "contig.exe" solution. My only recourse would be to do what you say. Restore the database and hope the physical fragmentation is reduced.
With the advent and acceptance of SSDs, this is all pointless. I'm starting to do more and more SSD implementations and when using those drives, fragmentation doesn't seem matter.
This is off subject, I've yet to try to defrag an SSD. I'll be that's lightening fast! I'm going to try that today!
You should probably hold off on those SSD defrags. SSDs store data across multiple NAND chips and locations, basically be design the drive will be fragmented. However, unlike your standard mechanical drive, there is no read/write head to move and "search" for the data so defragmentation is not much of a concern on an SSD drive. Also, on top of it not making much of a difference, a NAND chip cell is only good for a certain number of write cycles. Defragging an SSD will in effect reduce the lifespan of the drive.
- Edited by Chris Przekop Tuesday, March 11, 2014 5:38 PM


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This property has been removed by the agent. It may be let or temporarily removed from the market
2 bedroom semi-detached house to rentBramley Crescent, Madginford, Maidstone, Kent
£750 pcm| £173 pw fees apply
Property Description
Letting information:
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|31 July 2012 (1883 days ago)
Full description
Delightfully well maintained semi-detached bungalow situated on this sought after and popular residential development with an excellent selection of local amenities. L-Shaped Entrance Hall. Living Room. Well fitted Kitchen with appliances. Two good sized Bedrooms. Bathroom. Separate W.C. Long driveway providing parking for several vehicles leading to concrete sectional garage with a 40ft rear garden.
Room Dimensions
LIVING ROOM 17' into bay x 11'
BEDROOM 1 14'3" x 10'1"
BEDROOM 2 10' x 8'5
KITCHEN 11'5" x 10'1"
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In the mid-1890s, when the U.S economy was in a depression, news spread across the country that rich deposits of gold had been found in the Yukon and Klondike regions of Alaska and Canada. Thousands of people flocked to the frozen Northwest in the hopes of striking it rich. The voyage was dangerous and conditions in the remote gold fields were exceedingly harsh, but this didn't stop the unprecedented wave of migration that came to be known as the Yukon Gold Rush. Listen to hear about three individuals of the time: a prospector, a con man, and a detective.
Story Length: 8:01
© 2011 National Public Radio, Inc. Used with the permission of NPR. All rights reserved.
The Dust Bowl was one of the worst man-made environmental disasters. It turned the southern Great Plains of the U.S. into a desert. When the native prairie grass was pulled out and replaced with wheat fields, the loose soil had nothing to hold it. The dirt blew away in the wind, and as it traveled it gathered into enormous dust storms that choked people and animals with dirt. In this public radio story you will hear archival interviews with people who lived through the Dust Bowl. You also hear an early recording of the poem "Hard Luck Okie" which examines the reasons why people moved West.Read More
In the early 20th Century Americans streamed to the middle of the country because of the Homestead Acts. These were federal laws that gave people ownership of the land for free. In this audio story you will hear from people who grew up on homesteads in Montana in the early 20th century. Both families were fairly isolated and self-sufficient, working hard to make a living off the land, but their affection for that lifestyle is still strong.Read More
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PRZOOM - /newswire/ -
San Jose, CA, United States, 2005/09/27 - A comprehensive hands-on introduction to PLC technology.
During this 3-day Hands-On seminar, held October 2527, 05, the fear of shutting down a PLC system is overcome by spending approximately 60% of the time programming and uploading/downloading exercises to and from the PLC. You will learn about programming, connecting input/output devices, solving (elementary and then increasingly more complex) problems, and troubleshooting. You will gain a very thorough understanding of PLCs by taking this course.
You should attend if you are involved with the programming, installation, use, care, or economics associated with programmable logic controllers; including maintenance technicians and supervisors, engineers, operations, management, and field service personnel.
NTT has been the industry leader in hands-on industrial training for maintenance, operations and repair professionals for over twenty one years. NTT earned that position by providing clients with the most professional, value added, Hands-On training, from the most respected industry subject matter experts, on the latest equipment, for over 21 years! NTT consistently earns a 99.6% satisfaction rating from our clients. We have over 85% of the Fortune 500 training with us again and again! Without exception, NTT provides the most focused, information-rich industrial technical training available.
Agency / Source: National Technology Transfer, Inc.
Availability: All Regions (Including Int'l)
Traffic Booster: [/] Quick PRZOOM - Press & Newswire Visibility Checker
Distribution / Indexing: [+]


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SAMA Foreign Holdings
Country: Saudi Arabia
Established: N/A
Entity Structure: Fund in Central Bank
US$ Billion: 432.0*
Origin: Oil
Transparency Rating: 2
Some of the funds are managed by the Saudi Arabian Monetary Agency (SAMA), the central bank of the Kingdom of Saudi Arabia which was established in 1952. Many of the surplus oil revenues are invested in low-risk assets, such as Sovereign Debt.
*US$ 433.0 billion as of November 2008
News and Updates2/1/2008
SAMA's vice governor recently suggested that Kingdom of Saudi Arabia was planning a new sovereign fund which would invest in foreign securities.
WebsiteKingdom of Saudi Arabia Ministry of Finance
Saudi Monetary Agency
1. All figures quoted are from official sources, or, where the institutions concerned do not issue statistics of their holdings, from other publicly available sources.
Fund Information Feedback: please email email@example.com
Please read Fund Feedback Policy, only reply if you are representative of this Fund.
|Legal Notice © 2008 - 2010 Sovereign Wealth Fund Institute Inc. All Rights Reserved.


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Ryan to deliver speech in Ohio on helping middle class
freedomingood provo, UtahOct. 23, 2012 5:19 p.m.
Middle class, help yourselves by giving your boss a big raise.
Trust us, he won't spend it on imported cars, imported luxuries and German Yachts. He'll hire your brother and dozens more with it even if he has nothing for them to do.
And he certaily will not build a factory in China and fire all of you.
mcclark Salt Lake City, UTOct. 23, 2012 1:18 p.m.
Tax cuts for the wealthy, it worked so well for Bush, so its time to double down.


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My wonderful wife has stated that she will buy me a new keyboard for Xmas. I still am undecided on which to go with so need your guys help. Everyone talks about mechanical keyboards being amazing. One of my coworkers had one and said he couldn't take the clicks of it. I've also read that Cherry MX switches were the best to use for the least amount of noise.
Basically I've gone into information overload. Everyone talks about the DAS keyboards as being great, the Razer as being crap, and i think Corsair as being another decent choice. Never using a mechanical keyboard I am wondering 2 things:
Are the clicks loud enough to bother other people in the room?
Am I going to hate it?
Is the feel of the keyboard that much different that I should try one out at a store before buying one online?
Ok ... I realize that the questions will have different answers based on your own individual answers but thought I'd ask anyway.
EDIT: I'd like to keep the price around $100 but could go a bit more if necessary.
Do you have a store with demo models out? I know a lot of the gaming stuff isn't out at stores like Best Buy.
We have a store called Canada Computers. They have a demo of just about everything out. You can go see.
I have the k60 from corsair. I have to say that the open bottom is the best for getting rid of keyboard sludge. There's no pan, so one blast of air and every crumb is gone. Problem being, there are some hardware issues I've heard of. Repeating key, which I've had, but stops when you he the key next. They'll RMA for this, but it's not enoug of an issue for me. Happens rarely. My caps lock led is burned out. Again they'll RMA for this, but it's not enough of a hassle for me.
If I did it over again, I'd get the K90 for the backlight.
The clicks aren't that noticeable for me. It's more the key bottoming out with no case around it. It's way louder than an MS keyboard. Took some getting used to.
I'd say the big feature for me has nothing to do with the cherry switches. It's the clean factor of this design.
Oh, also the key swap. It comes with red, textured keys for 1-5 and WASD and a key puller tool. This helps my young sons use the WASD keys in minecraft.
Do you want/need the numpad?
I only ask because the CM Storm Quickfire Rapid is my fave budget(ish) mech keyboard.
*Also... you have no idea how proud I was of myself this afternoon for not going after the most obvious joke ever and asking if it has to be a keyboard.
My keyboard is no longer in production, but I hear tell that the new model is just as good.
The backlight is adjustable, and can even be turned off if you are bashful. It is not super loud, but has a good typist feel.
I like the Saitek keyboards because they tend to last me, there are not tons of functions on them to just break, and I can do work on them.
What I cannot speak to is Saitek brand's quality now that they are owned by Mad Catz.
I use the Azio Levetron Mech5, and it's one of the nicest keyboards I've ever used. It is mechanical and it feels great to the touch, for gaming, typing, you name it. I don't think it's loud enough to bother anyone but then I've always used mechanical keyboards myself so I might be desensitized to it.
The great thing about the Levetron is that it's very customizable. You can move the numpad to either side, or even remove it entirely (I have mine sitting between my monitors to give my keyboard a smaller footprint). It also has a rail system that lets you mount a set of 6 hotkeys (included) if you like, in a position that works best for you. I keep mine over the F1-F4 keys and angled slightly upward, so I can reach under it. Or you can remove that entirely if you like. The Levetron also has a volume control knob and a button to deactivate the Windows key. You connect it via one or two USB ports, but if you don't have anything else plugged into the keyboard itself you should be fine using just one. It's purely a matter of power use.
Azio has stated that they intend to release additional add-ons for the Levetron but I've yet to see any. The rail looks just like a rifle mount rail, so I kind of want to put a scope on it.
I hadn't seen the Mech5 before. It looks a little.. aggressive. I can vouch for mechanical keyboards though. I break out my old IBM clicky every now and again for LAN parties and the over-engineered heft on that thing satisfies.


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Samsung NV7 OPS review
The NV7 is very well constructed to the extent that it feels like it is almost a solid block of metal. The switchgear and general construction is similarly top-class. It has an unusual inteface that soon becomes intuitive and is not hard to use. An annoyance is that the image stabilisation system seems to switch itself off form time to time and it is easy to accidently fully press the shutter before focussing is finished. A more steady thinking approach gives reliable images and after a false start the camera quickly started performing well for me.
See this thread for more information:
Out of focus shots and blurring until I remembered to check that the IS was still set and wait until the sometimes slowish focus had locked in before fully pressing the shutter.
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Our friend Sean from the SGTreport.com has released an excellent interview with author James Wesley Rawles. The pair discuss the inevitable wave of inflation coming to the US as a result of the Fed's policies which James says will be "Weimar-style", which means HYPERINFLATION. Where it gets really scary is that precious few people are prepared and in James own words, "People have no idea what the collapse of Western civilization might look like."
Full interview below:
Part 2: 'People have no idea what COLLAPSE might look like'


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Lord, When Did We See You Hungry or Thirsty or a Stranger or Naked or Ill or in Prison?
By Deacon Keith Fournier
2/20/2013 (4 years ago)
Catholic Online (www.catholic.org)
The face of Jesus is found in the face of the poor, for those with eyes to see. The word of Jesus is spoken through the poor, for those who cultivate the ears to hear Him. The cry of Jesus is heard in the cry of the poor, at least for those who stop to listen. That is the deeper meaning behind this sobering scene recounting the last judgment recorded by the Evangelist Matthew in the 25th Chapter of his Gospel.
I was hungry and you fed me
By Deacon Keith Fournier
Catholic Online (www.catholic.org)
2/20/2013 (4 years ago)
Published in Year of Faith
Keywords: poverty, poor in spirit, holiness, Dorothy Day, henry Nouwen, matthew 25, last Judgement, holiness, Chiara Lubich, Catholic Worker Movement, Focolare, Lent, holiness, Deacon Keith Fournier
P>CHESAPEAKE, VA (Catholic Online) - I was drawn to my knees by the words of Jesus contained in the Gospel (Matt. 25: 31-46): "I was hungry, and you gave me food; I was thirsty, and you gave me something to drink; I was a stranger and you welcomed me; I was naked and you gave me clothing; I was sick and you took care of me; I was in prison, and you visited me."
How well I understand the question posed by his stunned disciples, "Lord, when did we see you hungry or thirsty or a stranger or naked or ill or in prison, and not minister to your needs." (Matthew 25.35-36) It was an extraordinary statement! However, as I have aged I have come to see the many faces of poverty and I am learning to recognize the face of Jesus revealed in them all.
Have you ever considered the significance of the fact that the same Jesus who promised to be with us always also told us that the poor would be with us always? That is because they are connected. Indeed, in a sense, they are one and the same - in a way that is revealed with the eyes of living faith. "The poor you will always have with you; but you will not always have me" (Jesus, Matthew 26:11) "And behold, I am with you always, until the end of the age." (Jesus, Matthew 28:20)
The face of Jesus is found in the face of the poor, for those with eyes to see. The word of Jesus is spoken through the poor, for those who cultivate the ears to hear Him. The cry of Jesus is heard in the cry of the poor, at least for those who stop to listen. That is the deeper meaning behind this sobering scene recounting the last judgment recorded by the Evangelist Matthew in the 25th Chapter of his Gospel:
"Then the king will say to those on his right, 'Come, you who are blessed by my Father. Inherit the kingdom prepared for you from the foundation of the world. For I was hungry and you gave me food, I was thirsty and you gave me drink, a stranger and you welcomed me, naked and you clothed me, ill and you cared for me, in prison and you visited me.'
"Then the righteous will answer him and say, 'Lord, when did we see you hungry and feed you, or thirsty and give you drink? When did we see you a stranger and welcome you, or naked and clothe you? When did we see you ill or in prison, and visit you?'And the king will say to them in reply, 'Amen, I say to you, whatever you did for one of these least brothers of mine, you did for me.'"
This scene follows what is called the Parable of the Talents (Matthew 25: 1- 28) where another sort of judgment is recorded. This one is a judgment concerning the contrasting way of life lived between two groups of people, those who believe that what they have is their own and those who understand that all that they have has been given - as a gift.
These two groups approach their relationship with the goods of this earth (which are all good because the Lord has made them) quite differently. The ones who were praised by the Master know the relationship they have with the Giver. They also know their obligations to bear fruit by living the call to love in deed and truth, the call to solidarity and stewardship, inherent in receiving those gifts.
These folks live their lives in gratitude. They look for ways to participate in the ongoing mission of the Lord. They know that He works now, through them. They understand what they truly have and they invest it by giving it away to others. Sadly, those who grasp on to the goods of the earth, thinking that they are their own and bury them, experience the barrenness of self centeredness and the hollowness of the empty pursuit of 'stuff'.
The point of this passage is as profound, in some respects, as the judgment scene. It participates in the same mystery. They both address matters of the heart and reveal what can be called the economy of heavenly scale. ""To anyone who has, more will be given, and he will grow rich; from anyone who has not, even what he has will be taken away." (Matthew 25:29)
Those who love the poor - like Jesus loved the poor- are given as a gift and instruction manual for the rest of us. They are a sign of the kingdom, making it present in their wake. They love in deed and truth. Dorothy Day, a heroic witness and prophetic voice of the 20th century, grasped this mystery so well. That is why she is moving forward in the cause for canonization.
She lived in the aftermath of the industrial age where human persons were too often as products to be used. Though some get stuck in her circuitous and intriguing journey into the fullness of the truth as found in the Catholic Church, her heroic witness is being considered by a Church which is built upon men and women who were profoundly converted through their encounter with Jesus Christ.
She gave herself away, living with the poor, because she truly understood and embraced her own poverty with brutal honesty. She learned to love in deed and truth. So too did her brother in that work of authentic solidarity, Peter Maurin. He once wrote with utter simplicity and searing honesty: "We cannot imitate the sacrifice of Christ on Calvary by trying to get all we can. We can only imitate the sacrifice of Christ on Calvary by trying to give all we can".
Another great Christian woman of the same age, Chiara Lubich, the foundress of the ecclesial movement Focolare, expressed the heart of this call to love in deed and truth:"Yes, love makes us be. We exist because we love. If we don't love, and every time we don't love, we are not, we do not exist ("Even what he has will be taken away"). There's nothing left to do but to love, without holding back. Only in this way will God give himself to us and with him will come the fullness of his gifts.
"Let us give concretely to those around us, knowing that by giving to them we are giving to God. Let's give always; let's give a smile, let's offer understanding, and forgiveness. Let's listen, let's share our knowledge, our availability; let's give our time, our talents, our ideas, our work; let's give our experience, our skills; let's share our goods with others so that we don't accumulate things and everything circulates."
"Our giving opens the hands of God and He, in his providence, fills us with such an abundance that we can give again, and give more, and then receive again, and in this way we can meet the immense needs of many."
The beloved disciple John wrote as an old man in his letters to the early churches dispersed because of persecution: "We know that we have passed from death to life because we love our brothers. Whoever does not love remains in death. Everyone who hates his brother is a murderer, and you know that no murderer has eternal life remaining in him."
"The way we came to know love was that he laid down his life for us; so we ought to lay down our lives for our brothers. If someone who has worldly means sees a brother in need and refuses him compassion, how can the love of God remain in him? Children, let us love not in word or speech but in deed and truth." (I John 3: 14-18)
I knew a woman in Virginia Beach, Virginia named Brenda McCormick. She touched my life and challenged me to the core concerning this truth. She was not an easy person to be around. Prophets rarely are. She went home to the Lord years ago. She once wrote these words to me:
"In the end, there are two kinds of poor people: those who already know they are poor and those who don't know yet. Here is the crisis: If the latter don't discover this before they leave this planet, they are doomed to be poor forever. What can those of us who already know we are poor do for those who don't know yet? Love them."
As we enter into Lent I am reflecting again on what it means to love in deed and in truth; and how it can open the Hands of God. It was said of the early disciples that they "turned the world upside down" with their preaching (Acts 17). Well, they still can; if we learn how to love as he loved. We are invited to learn to love with His Love.
Like the Master whom we follow, we are invited to become the least of these. The late Fr. Henri Nouwen once warned of what he called the "lure of upward mobility" and referred to it as the greatest sin of the age. He spoke of God's extraordinary love, revealed in the Incarnation of Jesus Christ, as an alternative, a "downward mobility."
How extraordinary is this love of God. How hard it is to comprehend its invitation. The God of the entire universe came among us as a man. He emptied Himself and took upon Himself our humanity. In His sacred humanity he lived a full and complete human life, walking in intimate communion with His Father. He now makes it possible for us to do the same.
Because He was fully God, Jesus accomplished for us what we could never have accomplished for ourselves, he redeemed us, set us free from the punishment merited by our sin, bridged the separation caused by sin, and capacitated us to live our lives differently by grace. He defeated the last enemy, death and overcame the evil one. He did all of this because He is Love Incarnate and He can do nothing else but love in word and in deed.
He now invites us to walk in His way, the way of "kenosis". This is a Greek word which cannot really be translated in English. It is a self-emptying love. Jesus invites us to become the least of these. St Paul writes of Jesus "Though He was in the form of God, He did not count equality with God something to be grasped. Rather, He emptied Himself" (Philippians 2) This emptying the Apostle refers to is "kenosis" in Greek.
Pope St Leo the Great once wrote of Jesus: "He took the nature of a servant without stain of sin, enlarging our humanity without diminishing his divinity. He emptied himself; though invisible he made himself visible, though Creator and Lord of all things he chose to be one of us mortal men. Yet this was the condescension of compassion, not the loss of omnipotence. So he, who in the nature of God had created man, became in the nature of a servant, man himself."
God became the least of these. Will we? Will we allow the truth revealed in the life, death and Resurrection of Jesus Christ to become our pattern for daily living? Will we cooperate with the grace of conversion and be emptied of ourselves for others? We are invited to experience this mystery of faith and to make it real during this Lent.
When we empty ourselves, He comes and takes up His residence within us. Then, we can become His arms, embracing the world; His legs, still walking its dusty streets; and His Heart, still beating with the Divine Compassion manifested in Jesus Christ, the One who became the least of these in order to bring all of us into the full communion of Love.
'Help give every student and teacher Free resources for a world-class moral Catholic education'
Copyright 2017 - Distributed by THE CALIFORNIA NETWORK
Pope Francis Prayer Intentions for SEPTEMBER 2017
Parishes. That our parishes, animated by a missionary spirit, may be places where faith is communicated and charity is seen.
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I gave my back to those who beat me, my cheeks to those who plucked my beard; My face I did not shield from buffets and spitting. HYTHE, ... continue reading
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Abbott Labs (NYSE:ABT) is taking next steps as part of its plans to strengthen its foothold in the fast-growing India's nutritional market. The company will be investing approximately $65 million toward building its first nutrition manufacturing facility in India's Gujarat state. [1] Recently, the company opened its first nutritional R&D center in India through a tie-up with Syngene, a contract research unit of Biocon, one of the country's leading biotech company. Below we take a look at how these events could impact Abbott, a diversified healthcare major with a vast array of pharmaceuticals and other medical products, including nutritionals and diagnostics in its portfolio.
While our current price estimate for Abbott Labs stands at $66, we are awaiting the company's 10-k filing before we revise our price estimate to reflect the recent developments.
See our complete analysis for Abbott Labs
- Abbott's Investors Eying The Value From Acquisitions
- What To Watch For In Abbott's Q2 Earnings
- What If St. Jude Medical Acquisition Doesn't Pan Out For Abbott?
- No Surprises In Abbott's Earnings, But Investors Need To Be Convinced Of Value Of Acquisitions
- Abbott Labs: What To Look For In Q1 Earnings
- Nutritional Segment Subdues Abbott's Q4'16 Growth, But Future Growth Prospects Remain Strong
India: A Key Market Among Fast Growing Emerging Markets
India has a large number of diabetic patients and it has also been grappling with the prevalence of malnutrition. Further, as its middle class continues to grow, discretionary spending is likely to increase. These reasons coupled with increased health awareness will drive demand for health supplements. This presents a huge opportunity and remains a key target for Abbott Labs. To tap this expected surge in demand, the company has plans to have a fully integrated nutritional business in India and opening a manufacturing facility is the next step in that strategy. The plant will produce a range of nutritional drinks such as Ensure for elderly people and PediaSure for kids.
The company recently opened a nutritional R&D center in India, which will help Abbott develop affordable nutrition products for malnutrition and diabetes while addressing local preferences for taste and texture. The company is also mulling to add local sales and distribution functions.
The company is eying other emerging markets to give a boost to its nutritional business. It is also building manufacturing facilities in China. On a similar note, the company recently struck a R&D deal with a Russian group . We believe that such moves will certainly help the company increase its penetration in emerging markets to boost sales. If Abbott's plan materializes, this could positively impact the value of its nutritional division, which currently contributes about 13% to our current price estimate.
Submit a Post at Trefis Powered by Data and Interactive Charts| Understand What Drives a Stock at TrefisNotes:
- After Teva, US-based pharma giant Abbott Laboratories enters Gujarat, Business Standard, August 13 2012 [↩]


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My nonmember friends have talked to me about things that go on in the temple. How do they know about them, and what should I say about them?
First of all, don't let your friends' questions bother you. Temple symbols and ordinances have reached the public in various ways over the years, primarily by people who have left the Church. But just because these things are known to people outside the Church does not mean that they are any less sacred. What's important is that we continue to hold them sacred and show our commitment to the Lord.
Second, if people ask you about temple ceremonies, you can truthfully say that you don't know much about them because you haven't experienced them yet. However, to clear up misunderstandings, you could explain that we go to the temple to make covenants with Heavenly Father and that it "helps us focus on the Savior, His role in our Heavenly Father's plan, and our commitment to follow Him" (True to the Faith [2004], 171). Temple symbols and ceremonies are sacred and should not be discussed publicly, nor can they be properly understood or appreciated outside the context of the temple.
To learn more, you can read the following resources, both of which are available in some languages on LDS.org :
The booklet Preparing to Enter the Holy Temple (2004).
The "Temples" entry in True to the Faith, pages 170–74.
Is it all right to call Church leaders by their first names?
Sometimes we get so close to our leaders that we are tempted to become casual in our relationships with them. While it is good to be friendly, it is also important to show proper respect for them and their callings. In the Church it is customary to refer to adults as "Brother" or "Sister," a greeting that both shows respect and reminds us that we are children of Heavenly Father. Other more formal titles, such as elder, bishop, or president, are also used as signs of respect. Full-time missionaries set a good example of this by referring to each other as "Elder" or "Sister."
It is important to be respectful to our Church leaders and remember that although they are our friends, in a Church setting we should honor their callings and show respect by referring to them as "Brother" or "Sister."
President Monson said that serving a full-time mission is a priesthood responsibility. What does that mean?
Last general conference President Thomas S. Monson said: "To young men of the Aaronic Priesthood and to you young men who are becoming elders: I repeat what prophets have long taught—that every worthy, able young man should prepare to serve a mission. Missionary service is a priesthood duty—an obligation the Lord expects of us who have been given so very much." 1
Part of receiving the priesthood is agreeing to take upon yourself the responsibilities and duties that come with it. As with any gift that Heavenly Father gives, He expects you to use the priesthood to bless others. "For of him unto whom much is given much is required" (D&C 82:3).
Holders of the Aaronic Priesthood are "to warn, expound, exhort, and teach, and invite all to come unto Christ" (D&C 20:59). As President Monson stated, serving a full-time mission is a duty of priesthood holders. On a mission you will devote all of your energy, time, and focus to fulfilling that duty: serving, preaching the gospel, and inviting all to come unto Christ. Of course, fulfilling your duty always comes with blessings. Your mission will be a time of great joy and spiritual growth.
Thomas S. Monson, "As We Meet Together Again," Liahona and Ensign, Nov. 2010, 5–6; emphasis added.
From left: photo illustrations by David Stoker, Steve Bunderson, and Robert Casey