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Levels of brominated flame retardants are increasing in U.S. populations, yet little data are available on body burdens of these and other persistent hormonally-active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function.
Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables.
Ethnically diverse cohorts of girls 6-to-8 years old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 36 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breastfeeding in adjusted models.
Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9–855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breastfed, whose mothers were younger, or whose caregivers (usually parents) were less educated. Girls in California had higher GMs than in Ohio for the pesticides and most PCB congeners, but the opposite for CB-99 and −118.
Several of these potential HAAs were detected in nearly all of these young girls, some at relatively high levels, with variation by geographic location and other demographic factors that may reflect exposure pathways. The higher PBDE levels in California likely reflect differences in fire regulation and safety codes, with potential policy implications.
During the last few decades, concern has grown about the health effects of exposure to environmental contaminants that have hormonally active properties. While some of the chemicals of original concern were banned in many Westernized countries (such as DDT/DDE and PCBs), they are persistent in the environment. More recently, levels of a class of brominated flame retardants, the polybrominated diphenyl ethers (PBDEs), have been found to be increasing in the environment and subsequently in human biospecimens, and are present at higher concentrations in human serum and milk in the U.S. than in Europe (Hites 2004; Norstrom et al. 2002; Sjodin et al. 2004a). In contrast, levels of PCBs have been declining since the 1970s (Sjodin et al. 2004a). The PBDE studies have tended to include only adults (Bradman et al. 2007a and b; Hites 2004; Petreas et al. 2002; Sjodin 2004a; Schecter et al. 2005; Thomsen et al. 2002) and although there is much data on PCBs and DDT/DDE in adults and newborns, levels of these compounds are not routinely monitored in children under age 12y. The Centers for Disease Control and Prevention (CDC 2005) reports concentrations of these potential hormonally active agents (HAAs) in older children (12–19y) in the National Health and Nutrition Examination Survey (NHANES); more recent data on PBDEs were published separately (Sjodin et al. 2008) and in the very recent new report (CDC 2009).
Exposure to these persistent compounds in children is primarily through the diet (including breast feeding), as well as dust or inhalation for PBDEs (Lorber 2008). As the reproductive system does not fully mature until later puberty during adolescence, chemicals that affect the endocrine system might potentially alter such development. The observed trend towards pubertal development occurring at younger ages (Hermann-Giddens et al. 1997; Euling et al, 2008) has raised the possibility that exogenous exposures may be contributing factors. Due to these concerns and the association of early menarche with increased risk of breast cancer, a study of determinants of puberty in girls is being conducted within the NIEHS/NCI-sponsored Breast Cancer and the Environment Research Centers (BCERC), which include transdisciplinary research collaborations integrated across biologic, epidemiologic, and community outreach projects. Of primary interest are exposures to potential HAAs in young girls before breast development (Hiatt et al. 2009). Working with community representatives, laboratory staff at the National Center for Environmental Health of the Centers for Disease Control and Prevention (CDC), and the relevant literature, we identified numerous compounds for evaluation in a small pilot sample of girls who provided urine and serum specimens (Pinney et al. 2008, Windham et al. 2008, Wolff et al. 2007a). Factors considered in determining which chemical families were subsequently measured in the entire cohort included high detection frequency and adequate variability. This current analysis focuses on persistent organo-halogenated compounds measured in serum, which was collected at two sites. To provide data lacking on children of this age (6–9y), our goal was to characterize the distribution of these compounds and to compare them by geographic and other common demographic variables.
In the BCERC epidemiologic studies, girls ages 6–8 years at enrollment are being followed to measure onset and progression of pubertal maturation, including breast and pubic hair development. This longitudinal study began in 2005 at three sites: 1) Mount Sinai School of Medicine, which recruited girls through clinics, schools, and neighborhood centers in East Harlem in New York City; 2) Cincinnati Children's Hospital/ University of Cincinnati, Ohio (abbreviated as OH site), which recruited through public and parochial schools in the greater Cincinnati metropolitan area and through the Breast Cancer Registry of Greater Cincinnati; and 3) the Kaiser Permanente Northern California group, which recruited members of the Kaiser Foundation Health Plan born and still residing in the San Francisco Bay area (abbreviated as the CA site). Eligibility criteria for the study included age 6–8 years, female sex, and no underlying endocrine-associated medical conditions. All sites obtained informed consent from parent or guardian and child assent, administered by each institution's IRB. Study designs and methods were standardized for most but not all components, as each Center retained some unique scientific aims or modified procedures for the unique circumstances of its population.
At the time of the baseline and subsequent annual visits, girls had a physical exam and primary care givers (usually a parent) completed detailed questionnaires on demographic and a wide variety of other factors potentially related to puberty. Girl's race and Hispanic ethnicity, highest education of a primary provider (usually a parent), household income, history of breast-feeding and maternal age at delivery were obtained from baseline questionnaires. For the purposes of this report, girl's race/ethnicity is classified into mutually exclusive categories in the following priority order: Black (regardless of ethnicity), Hispanic (including any race other than Black), non-Hispanic Asian or Pacific Islander, non-Hispanic White, or Other (the last three are summarized without the term "non-Hispanic" in the text). Height and weight were measured during the physical exam using calibrated scales and stadiometers by research staff that had been trained and certified uniformly across all three sites. Body mass index (BMI) was calculated as weight/height-squared (kg/m2) and then classified as <85th national percentile or ≥ 85th percentile, indicating risk for obesity (Himes and Dietz 1994), using age and sex-specific CDC growth charts (CDC 2000). Age and BMI were calculated for the time of the serum draw (in months and years).
Blood samples were collected only at the CA and OH sites using materials and procedures provided by the CDC, after which they were processed to serum and stored frozen at −80°C until shipment. Samples were collected over the course of a few years as recruitment continued (in OH) or some girls only provided serum at follow-up visits (in CA). Ohio generated 270 samples and California 348, with a mean sample volume of 1.9 mls, for determining the concentrations of 11 PBDE "congeners" (including 2,2',4,4',5,5'-hexabromobiphenyl), 35 PCB congeners, and nine organochlorine pesticides (o,p' and p,p'-DDT, the metabolite p,p'-DDE, hexachlorobenzene (HCB), beta and gamma-hexachlorocyclohexane (HCCH), oxychlordane, trans-nonachlor, and mirex). The highly sensitive laboratory techniques used by the CDC for measuring the selected exposure biomarkers have been published (Sjodin et al. 2004b). Briefly, the methodology includes automatic fortification of the samples with internal standards as well as formic acid and water for denaturation and dilution of the samples. The samples were extracted by solid phase extraction; removal of co-extracted lipids was performed on a silica:silica/sulfuric acid column. Final quantitative determination of the target analytes was performed by gas chromatography isotope dilution high resolution mass spectrometry (GC-IDHRMS). Blank samples (n=3) were included in every set of 24 unknowns and 3 quality control samples. Reported concentrations were blank-corrected. The limit of detection was determined as the highest of (i) the instrumental detection limit or (ii) 3xSD of the blank samples. Hence, the limit of detection is directly proportional to the sample volume and the lipid concentration of the serum and was determined individually for each serum sample and analyte. The available amount of sample ranged from 0.2g to 2g. Detection limits were typically in the low pg/g serum range or sub to low ng/g lipid. As an additional quality control measure, a pool of serum was purchased (from the Interstate Blood Bank in Ohio, assembled from females of mixed race in their 20's) and samples interspersed with approximately every 10 valid girls' samples at each site. Concentrations in this report are lipid-adjusted (ng/g lipid weight), with lipids determined using commercially available kits (Roche Diagnostic Corp) for measurement of total triglycerides and total cholesterol.
For each analyte, up to 618 girls provided samples, but seven were missing lipid values, three were not reportable by the lab and nine did not have questionnaire data, so they were excluded from further analyses. The distribution of each analyte (mean, median, standard deviation, range, etc) was examined and is reported for those in which more than 60% of samples were above the detection limits. In addition, geometric means (GMs) were calculated because of the non-normal distribution. Following prior practice (Wolff et al. 2005), for measurements below the limit of detection (LOD), we substituted the value LOD/√2 for calculation of descriptive statistics. We summed the individual concentrations for the six most frequently detected PCB and PBDE congeners, separately (CBs 99, 118, 138/158 (co-eluted), 153, 170, and180, labeled PCBsum; and BDEs 28, 47, 99, 100, 153, 154, labeled PBDEsum) and examined these variables similarly. We calculated a correlation matrix and Pearson correlation coefficients for the 17 compounds (including sums). Coefficients of variation (CVs) were calculated in the 52 quality control samples as SD/mean × 100.
Analysis by co-factors (categories of site, child's race/ethnicity, age and BMI, caregiver education and income, maternal age at delivery and menarche, and history of breast feeding) was conducted comparing primarily GM levels by t-tests and ANOVA. Twenty-five girls were missing data on one or more of these covariates. We then performed multivariate analyses using the General Linear Model (GLM) procedure that accommodates unbalanced designs including those factors significantly associated with body burden levels, except income because of its correlation with education. Because breast feeding may represent a direct source of exposure, we present results for most variables without breast feeding in the model, adding it to report results only for this variable. Generally, inclusion of breast feeding did not affect the other associations. The model yields adjusted geometric means and their differences from a selected reference category for each variable.
Age at blood draw ranged from 6–10 years (the only 10-year old had recently turned ten), with the majority aged 7–8 years old (Table 1). The sample was racially diverse with 52% white overall, and of fairly high socioeconomic status (SES) based on education level of the care-giver. About one-third of the girls had a BMI indicating risk for obesity and the majority had been breastfed (Table 1). There were some differences between the two sites with girls from CA being older at blood draw, having older mothers, more likely to be Asian or Hispanic, and breast-fed, than in the OH sample, but with a slightly lower level of care-giver education. The proportion of girls at risk for obesity was very similar in the two sites.
Seven of 11 PBDE congeners were detected among more than 60% of samples, five of these in more than 80%. BDE-47 had the highest concentration (GM 42.8 ng/g lipid), followed by BDE-153, then BDE-99 and BDE-100 (Table 2). Ten of 35 PCB congeners and three pesticides were also detected in more than 60% of the girls (Table 2). Among the pesticides, p,p'-DDE was measured in nearly all samples and at a factor of 10–50 times higher (GM 107.3 ng/g lipid) than the other pesticides. Ten PCB congeners were detected in more than 60% of samples with five detected in nearly all girls. PCB congeners 153 and 138/158 were measured at the highest concentrations (GM 8.1 and 6.1 ng/g lipid, respectively). Fifty-two similarly-labeled QC samples (non-fortified human serum) were included intermixed with the girls' samples. After excluding one QC outlier result, the coefficients of variation (CVs) for the blind QCs for those analytes detected in more than 75% of samples ranged from 4% (p,p'-DDE) to 36% (BDE-99). When the study samples from the same batch as the outlier blind QC sample were re-analyzed, the correlation between the original and repeated measurements ranged from 0.68 (CB-74) to 0.9996 (BDE-99), with an average of 0.95, so the original values were considered accurate for use.
The primary PBDE congener concentrations were significantly correlated with each other (Pearson r's > 0.6), with BDE-153 slightly less correlated than others but still significant. The primary PCB congeners were also significantly correlated with each other, with CB-153,-170,-180 and −138/158 particularly highly correlated (r>0.9). The pesticides were moderately correlated with each other (r's = 0.2–0.5, p<0.001). Across groups, the PCB sum was most strongly correlated with HCB and t-nonachlor levels, and somewhat less so with p,p'-DDE, with CB-118 the least correlated of the PCB congeners with pesticides. PBDE levels were not at all correlated with the PCB sum or individual congeners, except for BDE-153, which was the only PBDE congener significantly correlated with the pesticides.
The crude GM of the PBDE sum and all congeners except BDE-85 were significantly lower in girls from the OH than the CA site. Blacks tended to have the highest PBDE GM concentrations, followed closely by Hispanics, compared to Whites with the lowest. The PBDEsum was also lower in girls who were older, of high BMI, and with higher educated care-givers. Levels did not vary consistently by mother's age at delivery and whether the girl was breast-fed or by duration. In adjusted models including age, BMI, race, site, maternal age and care-giver education, most crude associations remained significant (table 3). CA girls had adjusted GMs that were significantly on the order of 30% higher than OH girls for all six frequently detected PBDE congeners. Blacks had significantly higher GMs than Whites for most congeners whereas adjusted levels in Hispanics were similar to Whites. There was a tendency to lower mean levels with high BMI or higher education, but not consistently statistically significant. Age of child or mother and breast feeding were generally not associated after adjustment.
For the PCBsum, the crude GM was significantly lower in girls from OH, but this varied by congener; the lower chlorinated congeners (CB-74, 99, 105, 118) showed higher GMs in OH and comprised a larger proportion of the PCB sum than in CA. This may be reflective of race/ethnicity differences as Asians tended to have the highest GMs of the more highly chlorinated congeners (CB-170, 180, and 187). Crude levels were higher in girls with older mothers or who were breastfed, and by longer duration of breast-feeding. After adjustment (table 4), GMs of several congeners and the sum were still higher in CA girls, but CB-99 and CB-118 were significantly lower in CA. Black and Hispanic girls had lower adjusted GMs for all six frequently-detected congeners, whereas Asian girls had similar GMs, as Whites. History of breastfeeding was consistently associated with higher GM PCB levels, approximately doubled for several congeners (CB-153, 170, 180), as was older maternal age, adjusting for each other. The association of higher PCB levels with higher education appeared to be independent of race. Adjusted GMs were lower among heavy girls, and somewhat so among older girls, although the later was not consistently statistically significant (table 4).
Crudely, the pesticides had similar descriptor patterns as the PCBs except by race. With adjustment, girls in CA again had higher levels, particularly of p,p'-DDE. The adjusted GM of p,p'-DDE was higher in Asians and Hispanics, compared to Whites, but not of HCB and t-nonachlor, while Blacks had the lowest GMs of all three compounds (table 4). GM levels of the pesticides decreased with child's age but increased with maternal age and somewhat so with care-giver education (attenuated by adjustment for breast-feeding). Girls who were breast-fed had significantly higher GM levels of all pesticides, up to 50% higher for p,p'-DDE.
Our results show that many of these potential hormonally-active agents, most of which have been little studied previously in children of this age, were detectable in a large proportion of young girls, some at relatively high levels. Concentrations of many, most consistently the PBDEs, varied by geographic location with higher levels found in the California site. There were variations by race, with Blacks having the highest mean PBDE levels, but about 50% lower mean PCB levels and slightly lower pesticide levels, than Whites, even after adjustment for other factors. Hispanics had significantly lower levels of PCBs as well, but higher levels of p,p'-DDE. Asians had similar levels to Whites of all compounds except p,p'-DDE, for which they had the highest GM. As compared to the other compounds, patterns for PBDE levels by the other descriptors differed, including for BMI, SES (as measured by care-giver education), maternal age at delivery and history of being breast-fed. The girls who provided serum specimens were similar demographically to those who did not, so our results for these characteristics should be generalizable to the entire sample.
This is the first study to examine individual PBDE levels in elementary school-aged children in the U.S., reporting mean and median values generally 2–10 times greater than earlier published data (Hites 2004; Petreas et al. 2002; Thomsen et al. 2002). Sjodin et al (2004a) reported increasing PBDE concentrations in pooled U.S. serum samples from 1985 to 2002 and Hites (2004) estimated an exponential increase by a factor of 100 in the last 30 years, or a doubling every 4–6 years. Furthermore, studies from the U.S. generally report higher levels than those from Japan and Europe, particularly for BDE-47. Our GM for BDE-47 (42.8 ng/g lipid) is 50 percent higher than that of recent (2003–2004) NHANES data for 12–19 year olds, with differences of a similar magnitude for BDEs- 99, 100, and 153 (table 2 and CDC 2009). The lack of detection of some congeners in a large proportion of girls should not be interpreted to suggest absence of the compound, but is dependent on assay sensitivity and sample volume available.
The higher PBDE levels in CA than OH suggest greater exposure, as the difference was not explained by other co-variates examined. A recent study of dust samples taken from homes in California and Massachusetts found PBDE levels were 3–9 times higher in CA (Zota et al. 2007). Unlike other states, California has a history of stringent regulations (CA 2000) regarding flammability of upholstered furniture that can only be met by the addition of flame retardants, such as PBDEs. The primary commercial BDE mixture used to meet the polyurethane standard has been pentaBDE, which contains mainly BDE-47 and BDE-99, but also BDE-100, BDE-153, and BDE-154; the congeners we detected most frequently.
House dust and diet are considered the primary sources of PBDE exposure and young children are more likely to have higher dust exposure due to mouthing and playing activities, as well as to be exposed via breast milk (Lorber 2008). Our generally higher levels may therefore also indicate young children at greater risk of exposure, as with some other environmental chemicals and supported by exposure pathway modeling (Lorber 2008). Confirming this likelihood, the youngest age group in the NHANES data (12–19y) generally had higher mean PBDE levels than those of older age groups (Sjodin et al. 2008) and in pooled serum samples, recent data from Australia showed children 7–12y had higher PBDE levels than adults over 30y, but lower than children 2–6y (Toms et al. 2009). An increase in levels from newborn to early childhood (up to age 3 or 4y) has been attributed to breast-feeding (Carrizo and Grimalt, 2007; Toms et al. 2009). However, we did not find significant differences by whether or duration girls were breastfed, nor by mother's age at delivery or child's age within our relatively narrow range. Thus by age 6 and older, differences in PBDE body burdens may be most reflective of post-natal environmental exposures that are continuing, including from dust and diet.
By race, we found significantly higher PBDE levels in Black than in White girls, with intermediate levels in Hispanics before adjustment, suggesting possible differences in exposure. There are few comparison data available; NHANES data are for all ages combined and are not adjusted, but do indicate that Mexican and African Americans had higher GMs than non-Hispanic Whites for BDE-47 and BDE-99, and the 95th percentile levels were particularly high for African Americans (Sjodin et al. 2008). A study of cord blood levels in Baltimore found Asians had lower mean BDE-47 and BDE-153 levels than non-Hispanic Whites, and African Americans initially had higher PBDE levels, but not after adjustment (Herbstman et al. 2007). The reasons for potentially higher levels in Blacks should be explored further, perhaps including differences in metabolism and environmental conditions, such as condition of housing and furniture, or take-home exposures from parental occupations.
Examining the organo-chlorine compounds, the median we report for p,p'-DDE (101.5 ng/g lipid) is similar to that reported in NHANES for 12–19 year olds during 1999–2002 and 2003–04 and that for hexachlorobenzene is slightly less (CDC 2009). For the other pesticides we examined, the majority (75–90%) of 12–19 year olds in NHANES data had levels below the detection limit, so GMs were not calculated. We thus had higher detection rates for trans-nonachlor (69%), B-hexachlorocyclohexane (36%), and p,p'-DDT (30%). The mean and maximum p,p'-DDE levels we report are higher than recently reported in pregnant women (88 and 622 ng/g respectively) in Sweden (Glynn et al. 2007), but as expected are much lower than in earlier cohorts of pregnant women (Hertz-Picciotto et al. 2005) and do not represent a comparable population.
For PCBs, our median levels tended to be similar, but slightly higher than, those in the recent NHANES data for 12–19 year olds (table 2, CDC 2009). Comparing studies of neurodevelopment in children, Longnecker et al. (2003) reported much higher median CB-153 levels in maternal serum ranging from about 30–140 ng/g in the U.S. and up to 450 ng/g in the Faroe Islands. Most of these samples are from much earlier cohorts or have established exposure sources.
GM levels were higher in CA than OH for the three pesticides most frequently detected and four of the six frequently detected PCB congeners, similar to PBDEs. Consistent with these results, in the Nurses Health Study, Laden et al. (1999) reported that mean DDE levels were higher in participants from the West than the Midwest. Our results were not explained by race or SES, but race categories do not describe immigrant status. Pesticide exposure patterns differ in countries outside the U.S. (Bradman et al. 2007b, Smith 1999), hence a larger influx of immigrants (e.g. the parents) to CA from developing countries in Latin American and Southeast Asia, where some of these pesticides are still used, may explain higher levels of persistent pesticides in their offspring, via placental transport or breast-feeding.
In NHANES data combining all ages (CDC 2009), levels of p,p'-DDE were higher among Mexican Americans than Blacks or Whites, consistent with our findings for Hispanic girls. As noted above, the higher DDE levels we find in Asians and Hispanics may reflect a higher proportion of immigrants. Also similar to our results, some of the PCB congener levels in NHANES were lower among Mexican Americans. In contrast to the PBDEs, we found lower PCB levels in Blacks, as well as lower pesticide levels, which were not evident in NHANES data. Other studies have suggested lower PCB levels in Black than in White gravidas, but results were inconsistent by adjustment and these are not comparable populations (Herbstman et al. 2007, Wolff et al. 2007b). Nor are the NHANES data, which are for all ages (>12) and genders combined, and Asians are not separated, so our data thus add important detail to the literature.
Our finding of an inverse relationship between BMI and several pesticides or PCBs is difficult to interpret as either a contributor to or consequence of chemical levels. We examined BMI because of changing growth and fat stores in children of this age (Wolff and Landrigan, 2002). Exposure to some of the compounds occurs through breast-feeding, which may affect later BMI. We observed a slight trend towards lower BMI among breast-fed girls, which was, however, not statistically significant. Furthermore, in models that control for breast-feeding, the inverse association of the chemicals with BMI persisted. To explore this further, we examined the relationship between height and the pesticides or the PCBsum (adjusting for the other co-variates) and also found an inverse relationship. Similarly, a study from Germany found that girls with higher DDE levels during childhood had reduced growth at age 10 and shorter height at age 8, but reported no associations with PCBs (Karmaus et al. 2001, 2002). Levels of these persistent chemicals in girls primarily represent in utero and lactational exposures from the mother, as well as possibly later childhood exposure from diet and other sources. Studies with data on maternal or early childhood PCB levels show inconsistent results with later childhood anthropometric measures (Blank et al. 2000; Hertz-Picciotto et al. 2005, Gladen et al. 2000; Guo et al. 1995), likely further complicated by pubertal status at the time of anthropometric measurement.
In adults, a complex pharmacokinetic model has been proposed to explain interaction between BMI, time since exposure and organochlorine concentrations in adipose tissue (Wolff and Anderson 1999), which may also explain some of the findings in girls. DDE levels were inversely related to BMI in nulliparous Chinese women (Perry MJ et al. 2005), but varied in other studies. PCB levels were also lower in obese women in at least one study (Herbstman et al. 2007), but not in another (Wolff et al. 2007b). These observations seem less likely to support an effect on growth in children and perhaps suggest a "dilution" effect, which we can examine further when the longitudinal data collection is complete. Unlike typical findings in adults and with maternal age in our study, we found that some of the PCBs and pesticide levels were lower in older children, likely reflecting tapering effects of exposure occurring trans-placentally or through breast-feeding.
In summary, our study provides data that was previously lacking on body burdens of HAAs in young children from a large, racially diverse population using the most sensitive assays now available. Similar to some studies (Bradman et al. 2007a, Herbstman et al. 2007), but not all, we did not see strong correlations between PBDEs and PCBs, nor were their descriptors consistent. The variation we found by race and BMI, which are both relevant to puberty, as well as by site, warrant further investigation, both with respect to puberty and to identify factors contributing to exposure.
Funding Sources: This work was funded by the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), NIH, DHHS to the Breast Cancer & the Environment Research Centers at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center (U01 ES012801) and the University of Cincinnati/Cincinnati Children's Hospital Medical Center (U01 ES12770), with support from the University of Cincinnati Center for Environmental Genetics (P30-ES006096), the CA Department of Public Health (CDPH), and the NIH/NCRR-sponsored UCSF Center for Translational Science Institute (UL1 RR024131). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, the NCI, the CDC, or the CDPH. Before initiation of the study, human subjects approval was obtained from the IRBs of the institutions carrying out subject recruitment and data collection, e.g. Kaiser Permanente, Northern California (Number: CN-04LKush-04-H, last re-approved on Oct. 14, 2008) and the University of Cincinnati (CCHMC IRB # 03-18-05, last re-approved on Nov 1, 2008).
We wish to acknowledge the contributions of numerous BCERC collaborators, including Drs. Mary Wolff, Susan Teitelbaum and Antonia Calafat, as well as the field staff at each site; Janice Barlow, M. Kathryn Brown and other members of the Community Outreach and Translation Core; and Dr. Gwen Collman. We thank Isaac J. Ergas, Lixia Zhang, Ling Shen, and Lusine Yaghjyan for initial data management and analyses.
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How do you build a supply for returning to work while breastfeeding?
Comments (8)
I pumped for 10 minutes after every feeding, and your body will make enough for baby, don't worry. How often will you be able to pump once you go back to work. It helped me to pump with DD schedule.
Me (33) DH (32) Married 9/12/2010
DD - 3/12 (6 lbs 3 oz / 18 1/2 in long)
DS - 3/14 (6 lbs 7 oz/ 19 1/2 in long)
I fed off one side at night & pumped the other in the morning bc I got the most out then ( engorged ). I put that in the freezer. So one feeding a day I freeze. I had only about 2w in the freezer. I went back to work yesterday but I was able to pump enough for today. I have formula just in case too. So I have a stash in the freezer & I rotate one frozen & replace it so it gets used. Today LO had 2 fesh bottles & one frozen. I pumped 3 so one went back into the freezer to keep a fresh freezer rotation. Then off days I'll add one to the freezer & have fresh for the first work day. I like to have at least 3 days worth in the freezer as back up. I'm not into freezing 100 bags.
In my world everyone's a pony & they eat rainbows & poop butterflies
I also pumped after the morning feeding.
Samantha and Hubby - After 2 losses, our rainbow baby boy arrived 8/7/12.
You won't need a huge stash for when you return to work. Try pumping first thing in the morning while baby nurses on the other side and then maybe two other times through the day after a nursing session. When you go back baby will only need 1-1.25 oz per hour of separation from you. Never more than 3 oz in the bottle and go to kellymom and print out the information on bottle feeding the breast baby for your caregivers to read. Ideally you need to pump every 3 hours rather than four to keep your supply up if possible.


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overall service is good, breakfast is good. and very friendly staff. only less in room maintanance. the shower room of my room looks like 2 star hotel facility and the glass are dirty. i hope aston manado can increase inroom cleanliness.
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/ Meniscus tear (cartilage)
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The long and the short of it
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It's a common style dilemma for the Christmas and summer party season - to go maxi or mini?
Quiet fashionista Michelle Williams rocks both looks and seems to base her style choice on the occasion.
For red carpet events the actress always goes long, and for a more casual look she opts for teeny weeny lengths that show of her pins.
Take a tip from Williams and keep your hemlines classy not trashy.
No matter the length of the skirt, Williams always manages to stay looking sweet and demure.
If it's short down below she always covers up on top, but if her skirt length is long then she has no qualms about baring her shoulders.
Maxi or mini lengths - which do you prefer on Michelle Williams?
- Stuff
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Letting God Into Every Room of Your Heart
When you become a Christian, something truly amazing happens: God comes to live inside your heart. You become the home of God. If we're going to really live the Christian life, we need to decide to surrender all of our heart
- 12/15/2012
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Our hotel made the reservation for us on a busy Friday night. It is a small restaurant with a quiet pleasant atmosphere in the Rocks. Service was friendly and attentive. Great specials and ample selection of seafood on the menu. I had the Barrimundi, my son the Snapper and my wife a seafood pie, and all of us spent much of the meal saying how much we enjoyed the food. Good selection of Australian wines. It was a great night out.
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I have a 1999 Cadillac Deville (base). The "check gas cap" sign came on in my car. I bought a new one but the sign is still on. When that light came on the "service engine soon" sign also came on, they both are still on is there a way to turn them off?
Saturday, November 27th, 2010 AT 2:43 PM


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One of Choice's Outstanding Academic Titles for 1999
The View from the Tower: Origins of an Antimodernist Imageby Theodore Ziolkowski
View All Available Formats & Editions
Setting out to locate modern turriphilia in its cultural context and exploring the biographical circumstances that motivated W.B. Yeats, Robinson Jeffers, R.M. Rilke and Carl G. Jung to choose unusual retreats, the author traces the emergence of a variety of symbolic associations with the proud towers of the past, ranging from spirituality and intellect to sexuality and sequestration. 25 halftones.
Editorial Reviews
Product Details
- 9780691059075
- Publisher:
- Princeton University Press
- Publication date:
- 08/24/1998
- Series:
- Princeton Legacy Library Series
- Pages:
- 217
- Product dimensions:
- 5.84(w) x 9.27(h) x 0.81(d)
Read an Excerpt
The View from the Tower
Origins of an Antimodernist Image
By Theodore Ziolkowski
PRINCETON UNIVERSITY PRESSCopyright © 1998 Princeton University Press
All rights reserved.
The Proud Towers
* 1 *
The vogue of tower habitation in the years immediately following World War I surely constitutes one of the more remarkable phenomena in the history of poetic ecology. Like Simeon the Stylite and his ascetic followers, who sought refuge from the temptations of late antiquity atop their pillars in the desert, these modern "turrites" took to their towers as strongholds of security in what they regarded as the wasteland of Western civilization. In 1919 William Butler Yeats and his family spent the first of several summers in Thoor Ballylee, a Norman castle twenty miles inland from the Atlantic coast of Ireland. The following year, on a bluff overlooking the Pacific near Carmel, Robinson Jeffers laid the first stones of Hawk Tower, where he was to live and write for the next forty years. In 1921 Rainer Maria Rilke moved into the Chateau de Muzot, the step-gabled thirteenth-century tower in the Swiss canton of Valais where he passed the remaining five years of his life. In 1923 Carl Gustav Jung built the squat tower on the upper Lake of Zurich that became the cornerstone of his compound at Bollingen and for four decades his private sanctuary of introspection.
Other artists and thinkers of the twentieth century also fancied towers. When Gerhart Hauptmann commissioned his villa in 1901 at Wiesenstein near Agnetendorf, he specified a corner tower, with a view of the Silesian forests, to which he liked to withdraw for meditation. But towers play no conspicuous role in his writings, and in any case he always went downstairs to the library to dictate his texts. Paul Hindemith lived from 1923 to 1927 in the "Cow-Herd's Tower" ("Kuhhirtenturm") on the city walls of Frankfurt-Sachsenhausen, but the opera and song cycle that he composed there offer no resonance of his abode. Similarly, off and on from 1927, when he became headmaster of the Beacon Hill School, until 1937, Bertrand Russell maintained his study in the tower of Telegraph House on the Sussex Downs—again with no discernible impact on his thought.
What distinguishes Yeats, Jeffers, Rilke, and Jung is the fact that they not only spent years living in towers; towers play a constitutive role, both literal and symbolic, in their writings. Whether these writers share any characteristics that might account for their common turriphilia, and whether by moving into towers they reified an image already prevalent in their works or, alternatively, by writing about towers internalized the reality of their lives—these are some of the questions to be addressed in the following pages.
* 2 *
Let us begin by asking precisely what we mean when we say "tower." The standard architectural definition—a structure whose height is disproportionate with reference to its base—does not get us very far. The towers inhabited by our four writers have spiritual dimensions rather than architectonic ones. In this respect they exemplify an ancient tradition. Joseph Campbell once suggested that "the most striking symbolic features of the earliest high culture centers of both the Old World and the New were the great temple towers and pyramids rising high above the humble rooftops clustered about their bases." All these towers—from the storied pagodas of the Far East and the stupas of Southeast Asia to the obelisks of Egypt and the great stepped temples of Central America—occupy a similar place in their respective cultures: they represent the cosmic mountain regarded as the home of deity and thus reunite symbolically a heaven and earth that were originally one. Just as the ancient Hebrews imagined Jehovah on Mount Horeb in the Sinai, the Greeks located their gods on Mount Olympus; the Indians situated Siva's earthly retreat on the mythic Mount Meru at the center of the world; Hindus, Buddhists, and Muslims alike venerated Adam's Peak in Sri Lanka; the Japanese regarded Mount Fuji as the habitation of the supreme Shinto deity; and Buddhist temples in Korea still feature a small shrine to the indigenous mountain god.
To the extent that upward-striving towers exemplify the human desire to transcend the restraints of temporal existence and restore the contact between heaven and earth that was shattered by the Fall, they differ profoundly in their religious function from the great pyramids of Egypt, whose stereometric mass invites our attention not upward but inward, where they enclose bodies and treasures. (Pyramids evolved in the fifth millennium B.C. from the dwarf walls that originally surrounded the sunken burial chambers of the inhabitants of the Nile Valley.) In its original religious capacity, therefore, the tower stands alone as the embodiment of pure vertical structure: its space neither contains nor functions. Fortress towers, which are not independent structures, came later, as did such functional forms as lighthouses, bell towers, watchtowers, guard towers, water towers, radio towers, and other modern adaptations.
* 3 *
Of the various towers that punctuated the landscape of the ancient world the oldest and, for Western civilization, most influential were the terrace temples of Mesopotamia. The great stepped tower that the Hebrews saw in Babylon when Nebuchadnezzar brought them there in 587 B.C. marked the high point of a tradition reaching back three or four thousand years. Why the early inhabitants of the Mesopotamian basin began building their temples on terraced elevations is still a matter of debate. According to one theory the Sumerians migrated to the plains of southern Mesopotamia from a mountainous land where they had been accustomed to worship their deities on heights; the terrace temples represented their effort to reproduce by artificial means the elevations that their spirituality required. Another view, taking the climatic conditions of southern Mesopotamia into account, proposes that frequent floods necessitated locating the temples on earthen elevations which, as they were repaired and improved, grew higher and higher. In any case, excavations have shown that the earliest strata go back to the fifth millennium. In the course of the fourth millennium, great terrace temples were erected in Eridu, Uruk, Nippur, Ur, and other centers of southern Mesopotamia—centuries before Babylon became a city of any importance.
At the peak of Sumerian civilization it was the function of these towering ziggurats to symbolize, as Campbell puts it, "the graded stages of a universal manifestation of divinity." As the worshiper climbed past the seven stepped terraces, he not only moved through the levels between earth and heaven as represented by the seven planetary deities but also advanced through the seven grades of human consciousness, until he reached the sanctuary containing the inner shrine that constituted the seat of whichever supreme deity was worshiped locally. At the same time, these spatiotemporal models of heavenly and earthly life also provided excellent observation posts for the priests, whose astronomical investigations caused the ziggurats, especially in the course of the first millennium B.C., to acquire a reputation as places of intellectual activity.
If the tower originally possessed an essentially religious or spiritual meaning and provided the locus for the encounter of god and mortals, the rituals symbolizing the reunification of heaven and earth had implications that led to two other important associations. According to Herodotus (1.181–82), who visited Babylon around 460 B.C., the spacious temple on the summit held a richly adorned couch of unusual size. "There is no statue of any kind set up in the place, nor is the chamber occupied of nights by any one but a single native woman, who, as the Chaldaeans, the priests of this god, affirm, is chosen for himself by the deity out of all the women of the land." Herodotus also reports, though he disclaims any belief in the story, that the god reputedly comes down in person and sleeps upon the couch with the priestess—a legend that probably goes back to an early stage when the ruler and the priestess reenacted ritually the symbolic reunification of heaven and earth. Good comparatist that he is, Herodotus relates this account to stories about the priestesses of the temple of Theban Zeus in Egypt and the temple of Apollo at Patara. In all these cases the woman is prohibited from intercourse with mortal men. We note, therefore, that the tower, initially a religious site, soon acquired connotations of sexuality as well as sequestration—connotations that have persisted down to the psychoanalytical theories of Freud and his followers.
The origins of Etemenanki, the great tower of Babylon located next to the ancient sanctuary of Marduk, are still obscure. According to prevailing opinion, construction of this largest of the Mesopotamian ziggurats may well have been undertaken during the reign of Nebuchadnezzar I (1123–1101 B.C.), who defeated the Elamites and recovered the great statue of Marduk that had been taken away as booty earlier in the century. In an effort to surpass all existing terrace temples, Nebuchadnezzar planned an edifice that rose to a height of ninety-one meters on a base of ninety-one by ninety-one meters. For five centuries, however, the massive structure remained uncompleted until Nebuchadnezzar II (605–562 B.C.) made it his great obligation to the god Marduk as well as his ancestors to complete Etemenanki.
The tower of Babylon was not identical with the Tower of Babel that entered Western consciousness through the text of the Old Testament. Chapter n of Genesis was written by the scribe known as J sometime in the tenth century B.C.—several hundred years before his descendants in the Babylonian Captivity toiled at the completion of Nebuchadnezzar's great project. Whether he was inspired by the sight of actual ziggurats and ruins or knew them only from literary tradition is not certain. In either case, the Hebrews of the tenth century would have been dumbfounded by the massive towers of Mesopotamia. Although the notion of the encounter with deity on great heights was not unknown to them—witness the story of Moses' ascent of Mount Horeb to receive the Tables of Law—the idea of erecting artificial mountains for that purpose was totally alien to them. Moreover, the Bible often depicts mountain heights as places of evil or temptation. According to Ezekiel (20.28–31), who was contemptuous of the fertility cults associated with high places, God was angered because the early Hebrews offered their sacrifices on mountaintops and "presented the provocation of their offering." In the New Testament, too, Satan takes Jesus to lofty places—the pinnacle of the temple and a very high mountain—in order to tempt him (Matt. 4.5–9). Failing to appreciate the religious significance of the Babylonian edifices, the Hebrews saw in them a manifestation of human arrogance—a view that might have been reinforced by the intellectual pretensions of the Babylonian astronomers. Certainly the Hebrews could only have been offended by the notion of a god who lowered himself to couple with an earthly priestess.
Accordingly, the exalted Sumerian view of the tower as an image for the ascent of consciousness and the locus for the encounter with the divine was completely inverted by the Hebrews, in whose moralistic imagination the ruined or uncompleted ziggurats suggested not the humble approach to one's god but an act of titanic arrogance punished by the god with destruction. "Come, let us build ourselves a city, and a tower with its top in the heavens, and let us make a name for ourselves, lest we be scattered abroad upon the face of the whole earth" (Gen. 11.4).
The appeal of this notion to the Hebrew mind is attested by the fact that this story, unlike many other legends in Genesis, such as the Garden of Paradise or the Flood, has no parallel in Babylonian myth and shows many signs of having been originally composed by a non-Babylonian writer. That a ziggurat should have been destroyed by a Babylonian deity whose cozy sanctuary it provided is much less likely than that it should have been shattered by the wrathful Jehovah of the early Hebrews. Most Babylonian texts evince pride in the building of cities and towers. The use of brick and bitumen as building materials would have seemed unusual only to an observer accustomed, like the residents of Palestine, to stone as the basic unit of construction. Finally, the biblical etymology—"Therefore is the name of it called Babel; because the LORD did there confound the language of all the earth ..." (Gen. 11:9)—makes sense only for a speaker who does not understand the Sumerian meaning of the name ("gate of god") and derives it instead from Hebrew balal ("to confuse"). In short, the legend was presumably invented by Hebrews emerging from the simplicity of nomadic existence as an account of the fragmentation of primitive unity into separate communities, as their response to the technological achievements of the more advanced Babylonian civilization, and as an indictment of human superbia vis-à-vis the divine.
* 4 *
By the time of the Babylonian Captivity and Herodotus's visit to Babylon, the tower—specifically in the form of the ziggurat—had accumulated several distinct associations that were to play a significant role in its cultural apprehension. Foremost among these was the tower as a place of religious or spiritual experience, to which was attached a secondary association of intellectual insight. Where the Hebrew mind saw the haughty aspiration to power, the Greek imagination detected evidences of sexuality. For centuries, however, these associations lay as dormant as the ruins of the Mesopotomian ziggurats themselves.
It is one of the oddities of architectural history that the tower, after having occupied such a prominent place during several millennia of Sumerian history, played virtually no role in classical antiquity. The Greeks, in accordance with their general aesthetic principles, rejected for their own purposes any structure as asymmetrical as the tower. Even in the Alexandrine period the great lighthouse of Alexandria, the Pharos, was regarded as such an idiosyncrasy that it was numbered among the seven wonders of the ancient world. While the Romans had towers, they lacked any appreciation for the freestanding, functionless tower and built only structures that had a practical purpose, such as lighthouses or watchtowers on fortresses. (These may have been modeled in part on the Minoan nuraghi, squat round defensive towers from the second millennium B.C. that they could see in Corsica, Sicily, and Southern Italy—but especially in Sardinia. These primordial towers, often erected on ancestral graves, also embodied a magical link to the dead.)
In their literature and folklore, however, both Greeks and Romans were acquainted with certain symbolic aspects of the tower. While Lucretius does not specify a tower, in De rerum natura he created an unforgettable image of the serene temples from which the wise may look down upon the tribulations of the world:
sed nil dulcius est bene quam munita tenere edita doctrina sapientum templa serena, despicere unde queas alios passimque videre errare atque viam palantis quaerere vitae....
(But there is nothing more pleasant than to inhabit lofty and serene sanctuaries, well fortified by the teachings of the wise, from which you may look down upon others and see them everywhere wandering astray and seeking in their erring the path of life.)
Evidences not of the tower but of the sacred mountain are conspicuous at the beginning of the story of Cupid and Psyche, as related by Apuleius in his second-century novel The Golden Ass (Metamorphoses). Psyche's parents, perplexed because their beautiful daughter has received no suitors, consult the oracle of Apollo, who tells them to expose her on the summit of a nearby mountain ("montis in excelsi scopulo, rex, siste puellam," 4.33), where she will be taken by a husband not of mortal seed ("nee ... mortali stirpe creatum").
Yet another example is evident in the story of Danaë, as we know it from Horace (Odes 3.16), where Acrisius, the king of Argos, confines his daughter in a bronze tower—"inclusam Danaën turris aenea"—because he has been informed by an oracle that a son borne by her would put him to death. His efforts to prevent Danaë from bearing a child turn out to be in vain because Jupiter, smitten by her beauty, enters her bed in the form of a shower of gold, and they conceive Perseus (who in fact fulfills the fateful prophecy years later). A secularization of the story of Danaë is evident in the widespread fairy tale of Rapunzel, who is shut up in a tower by a witch but nonetheless succeeds in getting herself pregnant by the handsome young prince who uses her golden tresses as a ladder on which he climbs up to her room. A similar combination of sequestration and the encounter with deity—this time without the motif of sexuality—is evident in the early Christian legend of Saint Barbara. The daughter of a heathen who kept her confined in a tower with two windows, she had a third window added to complete the Trinity and, for her Christian faith, suffered the resulting martyrdom. She is represented iconographically as holding, or standing in front of, a tower with three windows.
Excerpted from The View from the Tower by Theodore Ziolkowski. Copyright © 1998 Princeton University Press. Excerpted by permission of PRINCETON UNIVERSITY PRESS.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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Hi guys I need some help, so I'm getting my BA done in September and have decided to go with 355cc! My surgeon told me this will take me do a 10D and just wanted to know if there is any petite 5'2 girls with the same size implants out there that could show me before and afters of your procedures... READ MORE
27, 3 Kids, 110lb, 5'6" 300cc silicone - San Diego, CA
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27 Yrs Old, No Kids, Pre Op 32A , 445cc Silicone HP - Honolulu, HI
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text: Town House Cafe ADD TO Trip Planner Only farmer owned and supplied restaurant in Boone County; all meat is local from the all natural GarnerHill Farm; serves breakfast, lunch and dinner; burgers, sandwiches, tamales, shrimp, soup of the day, salads, side orders; breakfast menu features omelets, eggs, ham, bacon, steak, biscuits and gravy, waffles, hot cakes, French toast Get Directions Gas Calculator The pet-friendly icon means that any portion or all of the listing accepts pets. Please check with each individual property for rules and regulations. The handicapped accessible icon notates listings that are either partially or fully accessible. Please check with the property or properties you're interested in for specific information. Details Phone: 870-741-2130 Address: 119 West Rush AvenueHarrison, AR 72601 Payment Accepted: American Express Facilities & Features: Dining Type of Service: Menu Seating Capacity: 60 Things to Do In Harrison EXPLORE


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Honestabe wrote in Liverpool Chat
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Sissoko would be an even better signing than wijnaldum tbh. he was massive for france.
Nvm, it's because we cannot recall ward or fulton til the season is over now.
Apparently we signed a 39y/o gk on a free from augsburg? cool i guess? think mignolet will go anywhere?
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(Borussia Dortmund)
5 months ago
Hey, mate. 2 cool votes for being fan of the two coolest football clubs in the world (LFC and BVB). YNWA!
5 months ago
Cheers back atcha! Gotta' be honest, just jumped on the dortmund bandwagon a few years ago when I started watching klopp interviews (when lewendowski and gotze were still in the team) ich spreche ein wenig deutsch, aber mon français est meilleur que mon allemand
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Just listened to DJ's in heaven. LOL just lol. I like since I laid my burden down.
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Just saw this comment! (I always forget I have a wall.... Oops) but thanks!
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Hi. I have followed this forum for a while but just only create an account to comment. I like the way you comment so 2 cool votes for ya and please accept my friend request? See you around!
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Indeed my friend, YNWA!
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You have been put on status for trolling. I suggest you stay away from the Premier League chat. Doesn't seem like you are offering too much in there except starting fires
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Understood my friend, cheers and thanks for the heads up. Will learn from this!
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Alright, thanks for the understanding of the situation
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Advisory Report
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Advisory Report 2011-1: Preferred Industry Practice for Reporting VUCS as a Research Functional Expense
NACUBO Advisory Report 2011-01 clarifies when it is appropriate to classify costs associated with voluntary uncommitted cost sharing (VUCS) in the "research" functional expense category in an institution's audited external financial statements. NACUBO's Financial Accounting and Reporting Manual (FARM) defines the functional category of research as including "all expenses for activities specifically organized to produce research, whether commissioned by an agency external to the institution or separately budgeted by an organizational unit within the institution." Some institutions have relied on the term "separately budgeted" and included all amounts budgeted as research whether or not the budgeted amount represents the actual effort expended. Functional expense reporting should not be driven solely by budget allocations, but rather by the actual amounts spent on a particular function.
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