text:
Urinary Concentrations of Parabens and Serum Hormone Levels, Semen Quality Parameters, and Sperm DNA Damage
[do action="authors"]John D. Meeker1, Tiffany Yang1, Xiaoyun Ye2, Antonia M. Calafat2, Russ Hauser3,4[/do][do action="affiliations"]1 Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA, 2 Centers for Disease and Control and Prevention, Atlanta, Georgia, USA, 3 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA, 4 Vincent Memorial Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts, USA[/do]
[do action="citations"]Environ Health Perspect 119:252-257 (2010). http://dx.doi.org/10.1289/ehp.1002238 [online 28 September 2010][/do]
[do action="abstract"]
Background: Parabens are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Widespread human exposure to parabens has been recently documented, and some parabens have demonstrated adverse effects on male reproduction in animal studies. However, human epidemiologic studies are lacking.
Objective: We investigated relationships between urinary concentrations of parabens and markers of male reproductive health in an ongoing reproductive epidemiology study.
Methods: Urine samples collected from male partners attending an infertility clinic were analyzed for methyl paraben (MP), propyl paraben (PP), butyl paraben (BP), and bisphenol A (BPA). Associations with serum hormone levels (n = 167), semen quality parameters (n = 190), and sperm DNA damage measures (n = 132) were assessed using multivariable linear regression.
Results: Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP. We observed no statistically significant associations between MP or PP and the outcome measures. Categories of urinary BP concentration were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage (p for trend = 0.03). When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage (p for trend = 0.03). Assessment of paraben concentrations measured on repeated urine samples from a subset of the men (n = 78) revealed substantial temporal variability.
Conclusions: We found no evidence for a relationship between urinary parabens and hormone levels or semen quality, although intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage warrants further investigation.
[/do][do action="abstract"]Key words: biomarker, endocrine, epidemiology, exposure, fertility, reproduction, thyroid[/do]
[do action="notes-rule-above"]Address correspondence to J. Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S. Observatory St., Ann Arbor, MI 48109 USA. Telephone: (734) 764-7184. Fax: (734) 936-7283. E-mail: email@example.com[/do][do action="notes"]This work was supported by grants ES009718 and ES00002 from the National Institute of Environmental Health Sciences, National Institutes of Health.[/do][do action="notes"]The authors declare they have no actual or potential competing financial interests.[/do][do action="notes"]
We gratefully acknowledge A. Bishop, T. Jia, and J. Reidy (Centers for Disease Control and Prevention) for measuring the urinary concentrations of the parabens.
[/do][do action="notes"] Received 31 March 2010; accepted 28 September 2010; online 28 September 2010.[/do]
[do action="notes"] The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. [/do]
Parabens are esters of 4-hydroxybenzoic acid that are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food or beverage processing (Andersen 2008). It is likely that repeated contact with products or foods containing parabens leads to widespread human exposure through ingestion, inhalation, or dermal contact. Methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), and butyl paraben (BP) have recently been detected in a high proportion of urine samples collected as part of a national U.S. survey of exposure to environmental chemicals (Calafat et al. 2010).
Parabens are thought to possess low toxicity (Golden et al. 2005; Soni et al. 2005). However, some parabens may be estrogenic in vitro (Routledge et al. 1998), although with activity levels several orders of magnitude lower than that of estrogen. Recent experimental studies have reported that certain parabens may also act as antiandrogens (Chen et al. 2007; Darbre and Harvey 2008; Satoh et al. 2005), and there is limited evidence that parabens may affect thyroid function (Rousset 1981; Taxvig et al. 2008; Vo et al. 2010). Several animal studies have explored the impacts of parabens on male reproductive effects, with some reporting that exposure to BP and PP, but not MP, adversely affects spermatogenesis and endocrine function in rats or mice (Kang et al. 2002; Oishi 2001, 2002a; 2002b; 2004). Conversely, in another recent study, Hoberman et al. (2008) found no association between MP or BP and reproductive markers in rats. Based on these limited animal studies, in addition to the observation that paraben estrogenicity depends on the length of the alkyl side chain (Darbre and Harvey 2008), the reproductive toxicity potential of parabens for which widespread human exposure has been documented is thought to be BP > PP > EP > MP.
To our knowledge, no human studies have investigated the association between paraben exposure and measures of male reproduction. In the present study we assessed relationships between urinary concentrations of several parabens and a range of male reproductive health markers in an ongoing study of environmental determinants of reproductive health. We also considered the potential for interactions between parabens and another estrogenic xenobiotic, bisphenol A (BPA), for which we recently reported associations with reproductive measures in this population (Meeker et al. 2010a, 2010b).
Materials and Methods
Participants were male partners in subfertile couples seeking treatment between 2000 and 2004 from the Vincent Memorial Obstetrics and Gynecology Service. After the study procedures were explained and all questions answered, subjects signed an informed consent. Men between 18 and 55 years of age without postvasectomy status who presented to the Andrology Laboratory were eligible to participate. Of those approached, approximately 65% consented. Most men who declined to participate in the study cited lack of time on the day of their clinic visit as the reason for not participating. The study was approved by the human studies institutional review boards of MGH, Harvard School of Public Health, the Centers for Disease Control and Prevention (CDC), and the University of Michigan.
On the day of each subject's clinic visit, a single spot urine sample was collected into a sterile polypropylene cup. Because the temporal reliability of parabens in urine is unknown, second and third urine samples were collected from a subset of men at subsequent clinic visits. These samples were generally collected between 1 week and 2 months after the first sample. After measuring specific gravity (SG) using a handheld refractometer (National Instrument Co. Inc., Baltimore, MD), each urine sample was divided in aliquots and frozen at –80°C. Samples were shipped on dry ice overnight to the CDC, where concentrations of total (free + conjugated) MP, PP, BP, and BPA were measured using a modification of the approach described by Ye et al. (2006). EP was not measured because of low detection rates among the U.S. population (Calafat et al. 2010). The analytical method and results for BPA have been previously reported (Meeker et al. 2010a, 2010b). The conjugated species of BPA and parabens were first hydrolyzed in 100 μL of urine using β-glucuronidase/sulfatase (Helix pomatia, H1; Sigma Aldrich, St. Louis, MO). The target compounds were preconcentrated by online solid-phase extraction, separated from other urine components by reversed-phase high-performance liquid chromatography, and detected by atmospheric pressure chemical ionization/isotope dilution/tandem mass spectrometry with peak focusing (Ye et al. 2006). The limits of detection (LODs) were 1.0 μg/L for MP and 0.2 μg/L for PP and BP. Low-concentration (2.2–9.0 μg/L) and high-concentration (10.5–53.8 μg/L) quality control materials (QCLs and QCHs, respectively) were prepared with pooled human urine that was analyzed with standards, reagent blanks, and study samples. The precision of measurements, expressed as the relative SD of 55–66 measures, depending on the analyte, was 5.8–12.1% for QCLs and 4.4–5.6% for QCHs. Paraben concentrations were corrected for SG using the formula
Pc = P[(1.024 – 1)/(SG – 1)], [1]
where Pc is the SG-adjusted paraben concentration (nanograms per milliliter), P is the observed paraben concentration, and SG is the specific gravity of the urine sample.
One nonfasting blood sample was drawn between 0900 and 1600 hours on the same day and time that the first urine sample was collected. Blood samples were centrifuged, and the resulting serum was stored at –80°C until hormone analysis at the MGH Reproductive Endocrinology Laboratory. Serum testosterone, estradiol (E2), sex-hormone– binding globulin (SHBG), inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, free thyroxine (T4), total triiodothyronine (T3), and thyroid- stimulating hormone (TSH) were measured using sensitive immunoassay methods as described previously (Meeker et al. 2007). The free androgen index (FAI) was calculated as the molar ratio of total testosterone to SHBG. Free testosterone was also estimated using published methods (Vermeulen et al. 1999). The testosterone:LH ratio, a measure of Leydig cell function, was calculated by dividing testosterone (nanomoles per liter) by LH (international units per liter). The FSH:inhibin B and E2:testosterone ratios were also calculated as measures of Sertoli cell function and aromatase activity, respectively.
Onsite at MGH, semen was collected from each subject into a sterile plastic specimen cup after a recommended abstinence period of 48 hr. After liquefaction at 37°C for 20–60 min, semen quality parameters and motion characteristics were measured at the clinic.
Semen samples were analyzed for sperm concentration, motility, and motion parameters using a computer-aided semen analyzer (CASA; version 10HTM-IVOS; Hamilton-Thorne Research, Beverly, MA) as previously described (Meeker et al. 2004a, 2008). Total sperm count (106 per ejaculate) was calculated by multiplying sperm concentration (106/mL) by semen sample volume (milliliters). Motile sperm was defined as World Health Organization (WHO) grade "a" sperm (rapidly progressive with a velocity ≥ 25 μm/sec at 37°C) plus "b" grade sperm (slow/sluggish progressive with a velocity of ≥ 5 μm/sec but < 25 μm/sec) (WHO 1999). Of seven CASA motion variables measured, we included only three in our analysis [straight-line velocity (VSL), curvilinear velocity (VCL), and linearity (VSL/VCL × 100)] because of a high degree of dependence between several of the measures (Duty et al. 2004; Meeker et al. 2004a). Sperm morphology was assessed on two slides per specimen (with a minimum of 200 cells assessed per slide) with a Nikon microscope using an oil-immersion 100× objective (Nikon Company, Tokyo, Japan). We used strict Kruger scoring criteria to classify men as having normal or below normal morphology (Kruger et al. 1988).
The remaining unprocessed semen was frozen in 0.25 mL cryogenic straws (Cryo Bio System, IMV Technologies, San Diego, CA) by immersing the straws directly into liquid nitrogen (–196°C). Previous work in our laboratory showed that this freezing method produced comet assay results that were highly correlated with results from fresh, unfrozen samples (Duty et al. 2002). Semen samples were later analyzed in batches, where straws were thawed by gently shaking in a 37°C water bath for 10 sec, and the semen was immediately processed for the comet assay. To assess sperm DNA damage, we followed a comet assay procedure that has been previously described (Duty et al. 2003; Singh and Stephens 1998). After lysis, electrophoresis, and staining, we measured comet extent, tail distributed moment (TDM), and percent DNA located in the tail (Tail%) for 100 sperm in each semen sample using a fluorescence microscope and VisComet software (Impuls Computergestutzte Bildanalyse GmbH, Gilching, Germany). Comet extent is a measure of total comet length from the beginning of the head to the last visible pixel in the tail. Tail% is a measurement of the proportion of total DNA that is present in the comet tail (i.e., fragmented DNA that has migrated away from the comet head). TDM is an integrated value that takes into account both the distance and intensity of comet fragments:
where ΣI is the sum of all intensity values that belong to the head, body, or tail and X is the x-position of the intensity value.
We performed data analysis using SAS (version 9.1; SAS Institute Inc., Cary, NC). In preliminary data analysis, paraben concentrations and outcome measures were compared by demographic categories and other potentially important covariates using appropriate parametric or nonparametric tests to investigate the potential for confounding. Multivariable linear regression was used to explore relationships between urinary paraben concentrations and hormone levels, semen quality parameters, and sperm DNA damage measures. Serum concentrations of inhibin B, testosterone, free testosterone, and E2, along with semen volume, sperm motility, morphology, and all sperm motion and sperm DNA damage measures, closely approximated normality and were used in statistical models untransformed. The distribution of sperm count, sperm concentration, FSH, LH, SHBG, prolactin, TSH, and all calculated hormone ratios were positively skewed and transformed by the natural logarithm (ln) for statistical analyses. Urinary MP and PP concentrations were also ln transformed. For PP, MP, and BPA concentrations < LOD, we used an imputed value of LOD/2. Because of the high proportion of samples with BP values < LOD, a three-level ordinal variable was formed: all samples with concentrations < LOD were assigned to the lowest group, and two equally sized groups were formed among the samples with detectable concentrations to form the median- and high-exposure groups. Tests for trend were conducted for ordinal BP categories in regression models using integer values (0, 1, 2).
Inclusion of covariates in the multivariable models was based on statistical and biologic considerations (Kleinbaum et al. 1998). We included SG as a continuous variable in all models to adjust for urinary dilution. Age and body mass index (BMI) were also modeled as continuous variables, whereas abstinence period was treated as an ordinal categorical variable. Race (white vs. other), smoking status (current smoker vs. former or never smoker), and timing of the clinic visit (i.e., time of collection of urine/blood/semen samples) by season (winter vs. spring, summer, or fall) and by time of day (0900–1259 hours vs. 1300–1600 hours) were considered for inclusion in the models as dichotomous variables. Covariates with a p-value < 0.2 in their relationship with one or more parabens or at least one outcome measure in the preliminary bivariate analyses were included in a "full" model. Covariates with a p-value > 0.15 in full models for all measures within the three sets of outcomes (hormone levels, semen quality, sperm DNA damage) were removed from the final models. Models for all outcome measures within each of the three sets of outcomes were adjusted for the same covariates to maintain consistency. For the dependent variables of interest (urinary paraben concentrations), we considered p < 0.05 statistically significant. Because of the exploratory nature of the analysis, p-values < 0.1 were considered statistically suggestive.
Because repeated urine samples were available for a subset of the men, two sets of models were constructed: a) using only urinary paraben concentrations from a single urine sample collected on the same day as the serum sample; and b) using the geometric mean urinary paraben concentration for each participant, where between one and three values were used to calculate each individual's geometric mean (i.e., the geometric mean for men with only one value was equal to that single value). In further sensitivity analyses, the multivariable models were rerun after excluding men with highly concentrated or highly dilute urine samples (SG > 1.03 or < 1.01) (Teass et al. 1998), and when using SG-corrected paraben concentrations rather than uncorrected urinary paraben concentrations but including SG as a covariate. Finally, to assess temporal variability in urinary paraben concentrations, we calculated Spearman correlations for paraben concentrations in the first and second urine samples among men with two urine samples. Using paraben data from all men, we also calculated the intraclass correlation coefficient (ICC), which is the ratio of between-subject variability to total variability (total variability = between-subject variability + within-subject variability), using SAS PROC MIXED.
Demographic and outcome measure distribution data on the men who participated in the study have been described elsewhere (Meeker et al. 2010a, 2010b). Briefly, most men were white (84%) and were nonsmokers at the time of the clinic visit (90%). The mean (± SD) age and BMI were 36.7 ± 5.4 years and 27.4 ± 4.5, respectively. Median (25th, 75th percentile) values for sperm concentration, motility, and morphology were 100 million (24 million, 145 million) sperm/mL, 46% (26%, 66%) motile sperm, and 7% (3%, 10%) normal sperm, respectively.
Detection rates and distributions of uncorrected and SG-corrected urinary paraben concentrations from urine samples collected from 194 men on the same day as a serum sample (hormone levels) and/or semen sample (semen quality, sperm DNA damage) are presented in Table 1. Information on SG was missing for four urine samples. We detected MP in all samples and at the highest concentrations (median = 27.4 μg/L), followed by PP (median = 3.5 μg/L). BP was positively associated with age (Spearman r = 0.16; p = 0.03), but MP and PP were not. All three parabens were inversely associated with BMI (Spearman r, between –0.15 and –0.17; p-values < 0.05). Paraben concentrations were not associated with smoking status, time of day or season of urine sample collection, or duration of abstinence before semen sample collection. PP concentrations (p < 0.05), but not MP or BP concentrations (p > 0.05), were higher in nonwhite men than in white men. MP and PP concentrations were strongly correlated with one another (r = 0.82; p < 0.0001), and both were only weakly to moderately correlated with BP (both r = 0.39; p < 0.0001). Spearman correlation coefficients with urinary BPA were 0.29 for MP (p < 0.0001), 0.18 for PP (p = 0.01), and 0.11 for BP (p = 0.13).
Distribution of uncorrected and SG-corrected paraben concentrations in urine (μg/L) collected at the initial clinic visit.
In addition to the 194 urine samples collected at the same visit as serum/semen sample collection, a second urine sample was later collected from 78 of the men, and a third urine sample was collected from 4 men. The amount of time between consecutive urine samples ranged from 3 to 75 days, with a median (25th, 75th percentile) of 29 (27, 34) days. Among the 78 men who provided two urine samples, paraben concentrations in the first and second urine samples were weakly correlated for MP (Spearman r = 0.36; p = 0.003) and PP (r = 0.25; p = 0.03), and moderately correlated for BP (r = 0.46; p < 0.0001). However, these values increased when using SG-corrected concentrations (r = 0.46, 0.31, and 0.58, respectively). When considering all 272 urine samples with paraben concentrations measured, the ICC was 0.26 (SG-corrected, 0.35) for MP and 0.18 (SG-corrected, 0.26) for PP. We did not calculate ICC for BP because of the high proportion of nondetectable concentrations. For comparison, the ICC for BPA in these samples was 0.08 (SG-corrected, 0.13).
Urinary paraben, covariate, and outcome data were available from 167 men for hormone levels, 190 men for semen quality parameters, and 132 men for sperm DNA damage measures. In exploratory bivariate analyses, we found no statistically significant correlations between uncorrected or SG-corrected concentrations of MP or PP and hormone levels, semen quality parameters, or sperm DNA damage (data not shown). We also found no associations in multivariable linear regression models adjusted for age, BMI, smoking, time of day, and duration of abstinence (Tables 2 and 3), although we found a suggestive inverse relationship between MP and TSH (Table 2), a suggestive positive association between MP and Tail% (Table 3), and a suggestive inverse relationship between PP and TDM (Table 3). Results were similar when we also considered repeated urinary paraben concentrations measured in samples collected weeks or months after the initial urine sample, although the relationships between MP and TSH and Tail%, and between PP and TDM, were somewhat weakened (i.e., regression coefficients were closer to zero; data not shown). Our findings were also consistent when using SG-corrected paraben concentrations in the models, as well as when excluding concentrated or diluted urine samples with SG > 1.03 or < 1.01 (data not shown).
Adjusteda regression coefficients for change in serum hormone level associated with a ln-unit increase in urinary concentrations of MP or PP (n = 167).
Adjusteda linear regression coefficients for change in semen quality or sperm measures associated with a ln-unit increase in urinary concentrations of MP or PP (n = 190).
Aside from a suggestive positive association with FAI, categories of urinary BP were also not associated with hormone levels or semen quality parameters (Table 4). However, BP categories were associated with a dose-related increase in Tail% (p for trend = 0.03). Overall, the results for BP were also consistent when modeling geometric mean or SG-corrected paraben concentrations (data not shown). Because we previously reported a positive association between urinary BPA concentration and Tail% in these same men (Meeker et al. 2010b) and because BP and BPA may impart similar biological effects (e.g., estrogenic), we investigated the possibility of an interaction between the two urinary biomarkers on Tail%. When we included both BP categories and BPA quartiles in the multivariable model, both were associated with significant dose- dependent increases in Tail% (Figure 1). However, we found no evidence of interaction in stratified analyses or when including a BP × BPA interaction term in the model (p = 0.25; data not shown), although the statistical power of the test for interaction was low because of a fairly small sample size.
Adjusted linear regression coefficients for change in hormone levels (n = 167), semen quality (n = 190), and sperm DNA damage measure (n = 137) associated with categories of urinary BP.
Adjusted linear regression coefficients [95% confidence interval (CI)] for change in Tail% associated with categories of urinary BP and BPA included in the same model, adjusted for SG, age, BMI, abstinence period, current smoking, and time of collection of urine sample (n = 132).
As far as we are aware, this is the first human study to explore relationships between biomarkers of paraben exposure and male reproductive health. With the exception of a suggestive inverse association between MP and TSH, and a suggestive positive association between BP and FAI, we found no evidence for a relationship between MP, PP, or BP and altered hormone levels or conventional semen quality parameters. For sperm DNA damage, we observed a suggestive inverse association between PP and TDM, a suggestive positive association between MP and Tail%, and a statistically significant positive association between BP and Tail%. The relationship between BP and Tail% was not confounded by our recently reported relationship between urinary BPA concentrations and Tail% and may suggest additive effects on Tail% in relation to combined exposures to both BP and BPA. We also found an inverse relationship between BMI and urinary paraben concentrations, which may reflect differences in exposure (e.g., product use, diet) and/or paraben metabolism between people with differing BMI.
Our observation that the only statistically significant relationship involved BP is consistent with in vitro and animal data that suggest BP has greater reproductive toxicity potential than the other parabens examined in this study (Darbre and Harvey 2008; Golden et al. 2005). However, we did not observe inverse relationships between BP and sperm concentration and testosterone, which were reported in subchronic studies of rodents exposed to BP at around 4 weeks of age (Oishi 2001, 2002a) or in utero (Kang et al. 2002). Studies investigating whether BP causes DNA damage are limited, although BP has been associated with genotoxicity in CHO-K1 Chinese hamster ovary cells (Tayama et al. 2008) and increased cell death and injury in rat hepatocytes [National Toxicology Program (NTP) 2004]. Our observation of a positive association with sperm DNA damage, as measured by Tail%, may also be consistent with previous reports that BP may be a suitable vaginal contraceptive because of its ability to inhibit acrosin (an enzyme that aids sperm penetration into the oocyte during the fertilization process), most likely by damaging the sperm membrane (Song et al. 1991, 1989). For example, the primary cause of sperm DNA damage is likely to be oxidative stress (Aitken and De Iuliis 2010; Aitken et al. 2009), which can also damage the sperm membrane (Sharma et al. 2004). Although not well studied, parabens caused oxidative stress in skin cells (Nishizawa et al. 2006), and BP was associated with decreased cellular levels of glutathione and protein-sulfhydryl groups in rat hepatocytes (NTP 2004).
Although it is currently unclear which comet assay parameter is the most relevant measure of sperm DNA damage, Tail% has been shown to be proportional to the frequency of DNA strand breaks (Olive et al. 1990). Tail% may also represent a more sensitive measure of DNA damage than both TDM and comet extent, because Tail% continues to increase with increased DNA damage whereas comet extent may not (McKelvey-Martin et al. 1993). Inconsistent results between the various DNA damage measures obtained by the neutral comet assay regressed on the same independent variable have been observed in previous studies (Meeker et al. 2004b). It has been hypothesized that the different comet assay parameters may reflect different types of DNA strand breaks (Meeker et al. 2004b): Specifically, because of the lack of correlation between TDM and Tail%, a high TDM may be more likely to be associated with double-strand breaks, whereas a high Tail% may reflect single-strand breaks. Thus, in the present study, BP was positively associated with Tail%, which may reflect a relationship between BP and single-strand breaks. However, it is possible that this relationship was a chance finding in our data, and future research is needed in order to confirm our results.
Paraben exposures in the present study were likely representative of those found among men in the U.S. general population. Median and 95th percentile concentrations recently reported in males participating in the National Health and Nutrition Examination Survey (NHANES) for 2005–2006 (Calafat et al. 2010) were, respectively, 23.7 and 491 μg/L for MP, 2.3 and 125 μg/L for PP, and < LOD and 3.2 μg/L for BP, compared with 27.4 and 258 μg/L for MP, 3.5 and 95.5 μg/L for PP, and < LOD and 4.1 μg/L for BP in the present study. It should be noted that paraben exposure was much higher among women than among men in NHANES; females had 75th percentile urinary MP, PP, and BP concentrations that were 4, 7, and 12 times higher, respectively, than those of males (Calafat et al. 2010). Thus, human epidemiologic studies of female reproductive effects and adverse pregnancy outcomes in relation to paraben exposure should also be conducted.
We believe the present study is also the first to assess the temporal variability of paraben concentrations in urine. MP and PP concentrations were weakly correlated in repeated urine samples collected from the same individuals and had low ICCs (≤ 0.35). Repeated BP concentrations were moderately correlated. These measures of temporal reliability were greater than for urinary BPA concentrations among these men (Meeker et al. 2010a) but less than for concentrations of urinary metabolites of phthalates and nonpersistent pesticides among a different subset of men from the ongoing study (Hauser et al. 2004; Meeker et al. 2005). Thus, the lack of an association between urinary parabens and hormone levels or semen quality in the present study may be due to the presence of nondifferential (random) measurement error in our exposure estimates. Future studies should measure paraben concentrations in multiple urine samples collected over the exposure window of interest to reduce exposure measurement error. In the present study, the use of the geometric mean of repeated urinary paraben concentrations, when available, generally resulted in weaker associations with reproductive measures. This was consistent with our recent analysis of urinary BPA among these men (Meeker et al. 2010b). However, this may be because we collected the repeated urine samples weeks or months after the serum/semen samples used for measuring hormone levels, semen quality, and sperm DNA damage, whereas the exposure window of interest would likely be weeks or months leading up to the assessment of these measures.
The present study had a number of other limitations in addition to the likely presence of high temporal variability in paraben exposure levels. This includes the availability of only a single blood or semen sample for the assessment of hormone levels, semen quality, and sperm DNA damage, which may also vary over time. The cross-sectional design of the present analysis also restricts our ability to make conclusions regarding causal relationships, and the relatively small sample size provided low statistical power, which limited our ability to detect subtle relationships between urinary parabens and male reproductive health markers. For example, we observed adjusted regression coefficients of –0.08 and –0.06 for the relationships between sperm concentration and MP or PP, respectively. With our sample size of 190, we would have had 80% power to detect (α = 0.05) adjusted regression coefficients of approximately –0.22 and –0.15, respectively (Lenth 2009). Finally, because of the study's exploratory nature, we made a large number of statistical comparisons. Thus, we cannot rule out the possibility of chance findings to explain the observed relationship between BP and Tail%.
We found limited to no evidence of a relationship between paraben concentrations in urine and hormone levels or conventional semen quality parameters. However, it is possible that intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage, in addition to the potential for additive effects from combined exposures to BP and BPA, warrants further investigation. Added research on the potential for additive or multiplicative interactions between exposures to multiple environmental agents on male reproduction is also needed.
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- Meeker JD, Ehrlich S, Toth TL, Wright DL, Calafat AM, Trisini AT, et al. 2010. Semen quality and sperm DNA damage in relation to urinary bisphenol A in men from an infertility clinic. Reprod Toxicol 30(4):)532–539.doi:10.1016/j.reprotox.2010.07.005
- Meeker JD, Godfrey-Bailey L, Hauser R. 2007. Relationships between serum hormone levels and semen quality among men from an infertility clinic. J Androl 28(3):397–406.
- Meeker JD, Ryan L, Barr DB, Herrick RF, Bennett DH, Bravo R, et al. 2004. The relationship of urinary metabolites of carbaryl/naphthalene and chlorpyrifos with human semen quality. Environ Health Perspect 112:1665–1670.
- Meeker JD, Singh NP, Ryan L, Duty SM, Barr DB, Herrick RF, et al. 2004. Urinary levels of insecticide metabolites and DNA damage in human sperm. Hum Reprod 19(11):2573–2580.
- Nishizawa C, Takeshita K, Ueda J, Nakanishi I, Suzuki KT, Ozawa T. 2006. Reaction of para-hydroxybenzoic acid esters with singlet oxygen in the presence of glutathione produces glutathione conjugates of hydroquinone, potent inducers of oxidative stress. Free Radic Res 40:233–240.
- NTP (National Toxicology Program) 2004. Butylparaben (CAS No. 94-26-8): Final Review of Toxicological Literature. Research Triangle Park, NC:NTP.
- Oishi S.. 2001. Effects of butylparaben on the male reproductive system in rats. Toxicol Ind Health 17(1):31–39.
- Oishi S.. 2002. Effects of butyl paraben on the male reproductive system in mice. Arch Toxicol 76(7):423–429.
- Oishi S.. 2002. Effects of propyl paraben on the male reproductive system. Food Chem Toxicol 40(12):1807–1813.
- Oishi S.. 2004. Lack of spermatotoxic effects of methyl and ethyl esters of p-hydroxybenzoic acid in rats. Food Chem Toxicol 42(11):1845–1849.
- Olive PL, Banath JP, Durand RE. 1990. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay. Radiat Res 122:86–94.
- Rousset B.. 1981. Antithyroid effect of a food or drug preservative: 4-hydroxybenzoic acid methyl ester. Experientia 37(2):177–178.
- Routledge EJ, Parker J, Odum J, Ashby J, Sumpter JP. 1998. Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. Toxicol Appl Pharmacol 153(1):12–19.
- Satoh KN, Nonaka R, Ohyama K, Nagai K. 2005. Androgenic and antiandrogenic effects of alkylphenols and parabens assessed using the reporter gene assay with stably transfected CHO-K1 cells (AR-EcoScreen System). J Health Sci 51:557–568.
- Sharma RK, Said T, Agarwal A. 2004. Sperm DNA damage and its clinical relevance in assessing reproductive outcome. Asian J Androl 6:139–148.
- Singh NP, Stephens RE. 1998. X-Ray-induced DNA double-strand breaks in human sperm. Mutagenesis 13(1):75–79.
- Song BL, Li HY, Peng DR. 1989. In vitro spermicidal activity of parabens against human spermatozoa. Contraception 39(3):331–335.
- Song BL, Peng DR, Li HY, Zhang GH, Zhang J, Li KL, et al. 1991. Evaluation of the effect of butyl p-hydroxybenzoate on the proteolytic activity and membrane function of human spermatozoa. J Reprod Fertil 91(2):435–440.
- Soni MG, Carabin IG, Burdock GA. 2005. Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol 43(7):985–1015.
- Taxvig C, Vinggaard AM, Hass U, Axelstad M, Boberg J, Hansen PR, et al. 2008. Do parabens have the ability to interfere with steroidogenesis? Toxicol Sci 106(1):206–213.
- Tayama S, Nakagawa Y, Tayama K.. 2008. Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells. Mutat Res 649(1–2):114–125.
- Teass AW, Biagini RE, DeBord DG, Hull RD. 1998. Application of biological monitoring methods. In: NIOSH Manual of Analytical Methods. Cincinnati, OH:National Institute for Occupational Safety and Health. pp. 52–62.
- Vermeulen A, Verdonck L, Kaufman JM. 1999. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84(10):3666–3672.
- Vo TT, Yoo YM, Choi KC, Jeung EB. 2010. Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model. Reprod Toxicol 29(3):306–316.
- WHO (World Health Organization) 1999. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. New York:Cambridge University Press.
- Ye X, Kuklenyik Z, Bishop AM, Needham LL, Calafat AM. 2006. Quantification of the urinary concentrations of parabens in humans by on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 844(1):53–59.
Clarivate Analytics released the 2018 Journal Citation Reports, which tracks citations for articles published in 2015 and 2016. EHP's new Journal Impact Factor is 8.31, with a 5-Year Journal Impact Factor of 9.81. (more…)
We are pleased to present new and improved author guidelines! (more…)


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The Győr EYOF set a good example
The organizers of the Győr event presented their summary of the European Youth Olympic Games at the General Meeting of the European Olympic Committees (EOC) held in Zagreb. The future organizers and candidate cities present at the event were also eager to learn about the experiences of the Győr organizers.
Last weekend the Győr delegation delivered in Zagreb their detailed account of the organization of the EYOF. In the so-called Final Report, the organizing committee gave a summary of the figures linked to the event and they also summed up the tournament. The three-hour event provided the organizers of upcoming European Youth Olympic Festivals with an opportunity to put questions to the Győr organizers regarding their experiences, and in this manner to gather information and learn about the challenges involved in a more interactive manner. In addition to the senior officers of the EOC, the Sports Minister of Azerbaijan representing Baku, the 2019 organizer, the representatives of Kosice, the 2021 organizer and even the organizers of the upcoming Sarajevo Winter EYOF were present at the event. Zsolt Borkai, the Mayor of Győr and the President of the Organizing Committee of the EYOF delivered his speech in English on the third day of the EOC General Meeting, which was followed by a short film produced by the Győr organizers and providing a brief summary of the tournament. Győr received a lot of praise for setting the bar high, as far as the quality of the organization and of the venues was concerned. Zsolt Borkai thanked the European Olympic Committees, the Hungarian Government, the Hungarian Olympic Committee and the Town Council of Győr for their support, and the participating colleagues, the citizens of Győr and the volunteers for their hard work. He highlighted that the event received unanimous support in the host city. "The sports halls filled with spectators, the positive feedback received and the infrastructural developments that will continue to benefit the citizens of Győr confirmed that the organization of the EYOF was a good decision."
Janez Kocijancic EOC President thanked Zsolt Borkai for the fact that the town of Győr organized an EYOF of such high quality, highlighting that the venue of the tournament is beautiful city with a strong economy, excellent conditions and committed organizers. He also noted that he hopes that the EOC will again have the chance to cooperate with the city of Győr in the future . The President also summed up the overall opinion of the fifty participating nations, according to which the Győr tournament was the best organized and most captivating Summer EYOF ever staged.
Joseph Cassar, President of the Coordination Commission of the 2017 Győr EYOF has been closely monitoring event organization activities for years, in the light of which he emphasized that working together with the organizing team was a great experience and that they set the bar high in all respects. He also presented the major figures of the 2017 European Youth Olympic Festival, highlighting the media attention, which also underlines the quality of the event. (A total of 226 media representatives registered for the tournament, 149 from Hungary and 77 from abroad, representing a total of 22 countries.) He also noted that the participants returned home in a positive mood and took with them positive experiences and that he was sure that many will come back to Győr in the future.
The event was also attended by Krisztián Kulcsár HOC President, who stressed that attending the evaluation session as a Hungarian was a great experience, since everyone at the General Meeting of the European Olympic Committees was discussing the high quality organization of the tournament and of the unforgettable experiences gained here in Győr, Hungary at the first Olympic event ever staged in the country.
Zsolt Papp

subset: commoncrawl


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The Black Bat #3 (Preview)
in Comic Previews Comment
- Story by
- Brian Buccellato
- Art by
- Ronan Cliquet
- Cover by
- Ardian Syaf, Billy Tan, Jae Lee, and Joe Benitez
- Publisher
- Dynamite Entertainment
The Black Bat continues his redemptive quest to right the wrongs of his alter-ego Tony Quinn. But, before pursuing criminal kingpin Oliver Snate, Black Bat steals a page from Robin Hood to come up with the resources to fund his campaign. Also, Quinn's past unfolds as he recalls his first meeting with Carol Baldwin.


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New homepage on desktop
Latest News on Desktop
Services Page on Desktop
Services Page with Right-hand Navigation on Desktop
Our Portfolio on Desktop
Portrait and Landscape Homepage view on Tablet
Portrait and Landscape Footer view on Tablet
Portrait view of Services page and Landscape view of Timeline on Tablet
Portrait and Landscape Contact Us Form View on Tablet
Our Portfolio View on Tablet
Footer and Homepage on iPhone
Navigation and Timeline on an iPhone
Portfolio and Right-hand Navigation on an iPhone
Services Page and Homepage on an iPhone
PSP's brief to its internal Design and Rebranding Team and Web Development Team was to create a website that better promoted PSP's products and services. The aim was to promote more clearly, PSP's professionalism, its commercial approach and unrivalled commitment to quality. The re-launch also needed to better reflect the recent growth and success of PSP's products which are VISION CRM, Outlook Email Tracker and EX-AM Portal.Specific functionality required:
The success of this project was to be measured by an increase in the number of enquiries generated over time.
PSP's Design and Rebranding Team and Web Development Team came up with a solution to meet PSP's requirements.They created a new more professional looking, suite of 'next generation' Responsive Websites, to better communicate PSP's Products and Services, its Portfolio of clients and case studies, with an intuitively designed navigation to work across all devices. The more streamlined top menu bar, gives visitors access to key information more quickly. The new right-hand navigation bar gives visitors quick access to PSP's Knowledge Hub and the latest news, with deep-links to areas such as History, Our Team and the Contact page. The 3 new satellite websites created for each of PSP's Products, gives each one a clear brand identity. These new websites were launched as distinct product sites with their own URL to be indexed by the Search Engines, but accessible via the main PSP website. The approach of giving each product its own front door has helped to communicate the key features, benefits, case studies and testimonials in a clear and concise way. Each website also gives visitors easy access to a video overview, a downloadable product brochure and product enquiry form.The Web Development Team used the Bootstrap framework to deliver the Responsive Design, integrated with the latest version of EPiServer on .NET to create a powerful back-end CMS for the PSP Marketing Team. Care and attention was taken to ensure that the newly launched product sites were well sign-posted from the main PSP site, with all re-directs set up to maintain the Search Engine Indexes.The whole project, took just 5 weeks to complete and included specification writing, development of the sites, quality assurance and user acceptance testing, as well as the final deployment.Benefits


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Friday, September 26, 2008
Two in One
For this dress I used Simplicity pattern number 5279 (with a few added touches of my own.) I'd really like to share them with you now, but my little one has just awoken EARLY from a nap! Fooey. So in the next coming days look for tutorials on the pintucked bodice, the freezer paper stenciled bird, and the ruffled pinafore cap sleeves.
5 comments:
- lindzandrob said...
That dress turned out super cute! And i love how you made it so she could wear it for more than just Halloween. Good work!
- September 26, 2008 at 3:50 PM
- Kacey Randolph said...
OOOOH! So sweet! I cannot WAIT for the tutorial. I'm working up the courage to make Ruby Jane's first dress. I'm a novice, but I have a vision. That must count for something right? :o) I will be using yoru tutorial for sure...and maybe begging for some help! :o)
- September 26, 2008 at 6:30 PM
- Lyssa said...
Holy Canolli!! That is gorgeous and to smart to make it into 2 dresses. You are amazing with the sewing machine.
You pop out things left and right, how do you have the time?!
- September 26, 2008 at 7:58 PM
- Shana said...
So adorable! I love your blog. Keep up the good work!
- September 26, 2008 at 10:00 PM
- Rachel said...
You rock! Can't wait to see Allie in it!! She is just so cute--started smiling now. I'll get pics up on the blog soon. . . hopefully!!
Thanks for thinking of Allie! I love that it's two in one. How clever of you! You're amazing.
Love you!!!
- September 29, 2008 at 10:17 PM


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Stories about "Philosophy"
Video: Emilio Valadez '18 and the philosophy of lunch
Tuesday, May 15, 2018 7:47 pm
Amidst a "constellation of humans" in Commons at noontime, Emilio Valadez '18 is nourished by something greater than lunch.
What I mean when I say: 'Disposition,' with Lauren Ashwell
Friday, March 18, 2016 9:55 am
Philosopher Lauren Ashwell puts a metaphysical spin on an everyday term.
2014 Fulbright recipients: Ashley Lepre
Wednesday, May 21, 2014 10:05 am
Ashley Lepre '13 is one of Bates' 10 2014 Fulbright recipients.
2014 Fulbright recipients: John Stewart
Wednesday, May 21, 2014 9:31 am
John Stewart '14 is one of Bates' 10 Fulbright recipients for 2014.
'Agent provocateur' Thomas Tracy is 2014 Kroepsch honoree for excellence in teaching
Friday, February 28, 2014 5:56 am
For students, the intrinsic value of studying philosophy is a "richer and more interesting life."
Philosophy, Fall 2013
Thursday, July 25, 2013 1:59 pm
The Department of Philosophy is pleased to welcome Paul Schofield to the...
Researcher Allison Mann '08 keeps 'Mad Men' real
Thursday, June 27, 2013 10:48 am
Mann upholds the show's "well-earned reputation for authenticity and for mining the tumultuous history of the 1960s."
Campus Construction Update: June 7, 2011
Monday, June 6, 2011 2:14 pm
Like sands through the hourglass, so are the final days of the renovation of Hedge and Roger Williams halls. On Monday, June 27, faculty in philosophy, religious studies and environmental studies will receive key-card access to the renovated Hedge Hall and be able to start settling into their spiffy new offices. Four weeks later, July 25 is moving day for staff of the Language Resource Center and Off-Campus Study office and the faculty of the foreign-language programs that will occupy Roger Williams Hall.
$150,000 grant from Alden Trust supports Hedge-Bill renovations
Wednesday, December 8, 2010 2:05 pm
As Bates continues to transform two 19th-century residence halls into state-of-the-art academic buildings, the college has received a $150,000 grant from the George I. Alden Trust to support the renovation project.
Daily Series: Lambright '12 explores the African immigrant experience in Guangzhou, China
Monday, September 20, 2010 4:19 pm
As summer enters its final week, we are sharing stories from students...


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Vagina searches and other reasons the war on marijuana must end in America
The simplest evidence that the nationwide war on marijuana is a failure is this: Four states and D.C. have some level of legal marijuana with state-licensed growing and sales underway or on the books. End of the war ... but only here and there.
To witness the full scope of how silly and damaging the war on pot continues to be in the hodge-podge of states and localities still waging it, just sign up for a Google news alert pegged to "marijuana" (or in Bing or what have you). It'll flood your inbox, but you'll also learn a lot, most of it not very edifying.
Two recent examples from that list, and one I accidentally heard on an NPR program, nicely demonstrate the three main reasons the war is more than just bad public policy — it's injustice or un-justice or whatever the opposite of justice is.
Is pot THAT dangerous?
The first I'm calling the vagina search. It's the story of a heart-rending invasion of a person's body, in public ... in a gas station parking lot. Why did police officers pin a woman down and search her vagina in public earlier this summer? Why, for marijuana of course. Here's the gist of the story:
A deputy with the Harris County Sheriff's Department in Texas pulls a car over, thinks he smells pot. Searches car, no pot. So he calls in two other deputies (it matters that they were female?), who force Charnesia Corley, 21, down on a gas station parking lot and digitally probe her vagina, searching for the "destroyer of youth."
Really? Wow.
The police say they found .02 ounces of marijuana "on her." No one has said where the pot was found or proved that it even existed, and the charges of resisting arrest and possession have been dismissed. So, class, what have we learned? Well, here's the salient part from the Washington Post:
Keep in mind that under Texas law, it takes more than four ounces of marijuana to bring a felony charge. (Photo: This is what four ounces of marijuana looks like.)
It seems doubtful that a woman could be casually driving around with that much marijuana stuffed into her vagina. So Corley was forced to the ground, stripped, and penetrated to search for evidence that at worst would have amounted to a misdemeanor. Which means that the Harris County Sheriff's Department believes it's perfectly acceptable to allow a stranger to forcibly probe a woman's vagina in order to prevent her from possessing a personal-use quantity of marijuana. And even that happened without a warrant, based only on one deputy's claim to have smelled the drug.
When even the suspicion of marijuana, legal in four states, remember, can lead to this type of letter-of-the-law violation of basic human dignity, one has to ask: Is it worth it?
Does the act of enforcing this law cause far more harm (randomly, here and there across the land) than the drug itself?
How can the answer be "No"?
One can say "No" and talk about "the safety of children" and how we all have to obey the law, whether we agree or not. But what if police were handcuffing and beating people to get them to admit they were speeding? Wouldn't that be OK, too? Of course not. For one, there are no federally enforced speed limits to hide behind.
So, unlike for speeding, local jurisdictions have a blank check when it comes to marijuana "investigations," because the Department of Justice is complicit in every one of these vaginal searches (of which there appear to hundreds, if not thousands, a year). The feds do not step in and investigate violations of rights when it comes to marijuana.
It's a war, after all.
Armored midnight raiders
The second example is just one of who knows how many bizarrely over-armed, middle-of-the-night, no-knock raids that strike like lighting ... randomly, just here and there ... causing great harm to innocent and guilty alike. This one from Aug. 17 jumped out at me because of the setting and result.
An HIV-positive guy who also has cancer and hepatitis C is living on his "remote and isolated" property with his son and wife in Arizona, a state with legal medical marijuana. He and his son have official medical marijuana cards. An Apache County-led task force of some 60 law officers, including SWAT teams with armored vehicles and the works, storm his property at 4 in the morning.
Here's a local news account:
"I was telling them from the moment I was standing there underneath the lights of their tanks, 'We are card-holding medical marijuana patients,'" Gregg Levendoski told a local TV station. "They told me, 'I don't care.'"
OK, fine. The law's the law:
"They are violating the law," Commander Lance Spivey of the Apache County Sheriff's Office said on the day of the raid. "Even if it is medical marijuana like they are claiming, there are rules and regulations they must follow."
The officers claim they found nine plants over the 12-per-card limit the Levendoski family could legally have. Levendoski says it's not true.
Punchline: With 60 officers in trailers, vans and armored trucks storming the countryside looking for pot, this is what the big catch of the day came down to:
According to Spivey, with voter-approved medical marijuana now the law in the state, Arizona law officers are in the difficult position (of) Mtrying to determine what's legal and what's not. But at least one of the properties and its owners, Spivey says, is clearly in violation of the law's 12-plant limit. It's a property where Spivey says 36 plants were seized, 3 firearms were confiscated and 3 people were arrested.
Now note, only nine plants were illegal (if they were there at all ... the officers still have to prove it). And the three arrests were the deathly sick guy, his wife and kid.
Was it worth it?
Clearly, these officers had to have done some basic investigation to determine this person had marijuana on his property. So, they must have known enough about the property to know it wasn't a hideout for the heavily armed Mexican cartel, but rather the rural home of some really sick guy with possibly a few too many plants.
They couldn't have gone up to the property in the middle of the day, at his remote and isolated home, and had a conversation with the guy? Nope, because the drug war myth is that anyone and everyone with a joint or pot plant will take refuge in a machine-gun nest and fight to the death ... even in a state with clear medical marijuana laws.
Will the DOJ investigate this military-style invasion? Nope, because it is complicit in the raid and the perpetuation of the obviously stupid use of military tactics to pluck nine plants out of the ground.
White girl alarm
The last example is the most important, though less immediately obvious. It is notable both for the innocent, well-meaningness of it and that it concerns heroin — a drug vastly more dangerous than marijuana (even the feds now admit it). I heard the conversation on the radio while running errands ... and it hit me on the side of the head like a cop's baton. See what it does to you:
The host of NPR's Here and Now is talking about the White House's new effort to push treatment over arrest in the effort to stem the rise of heroin-related deaths. The host is talking with Timothy Cameron, sheriff in St. Mary's County, Maryland, and a member of Maryland's Heroin and Opioid Emergency Task Force.
He says:
"In 2014, we had 96 non-lethal prescription overdose cases, and we had two fatal overdose cases. In 2008 we had 102 non-lethal overdoses but 17 lethal overdoses and that opened the door for heroin." (I believe he's saying less prescription abuse meant more heroin use.)
Host: "Who are these people?"
"Well, that was the most alarming thing. When you look at our county it was certainly not the lowest socio-economic level of our community. It was in good homes. It was in the affluent portions of our county. It was young, white females. So, that was the alarming thing, was our young people were dying from overdoses of heroin. So, it took a complete mobilization of our community to realize that we needed to talk about this openly. And that it was not just a law enforcement issue, it's a public health issue."
Just take a second and unpack that statement (the host didn't).
Cameron means something generous: It's such a big problem that it's showing up where one doesn't expect it. That's all he means on the surface of it. But, there's the entire spectrum of the unjust war on drugs (esp. marijuana) in there, too.
It's not until white girls from good homes start getting into trouble that we, all of a sudden, need to start thinking of drug use as a "public health issue." Again, that's not what he's trying to say. But it's the reality of it. Busting down doors, dragging kids off the streets for possession and selling ... that makes sense in those "lowest socio-economic" neighborhoods. Toss in some white kids from good homes and that's something else all together.
Dear Congress and President Obama
The war on marijuana has been waged mostly against minorities and poor people and that's what everyone expects, even with a drug not even remotely as dangerous as heroin (or beer, for that matter). However, when suddenly it dawns on the white middle class that a lot of people they know use marijuana and might as well be taxed for it, the law changes.
But only here and there.
The war has created an injustice so ingrained and so hidden in our language and culture that this well-meaning officer, his community and even the NPR host aren't fazed by the obvious and ruinous implications of cracking down on poor people while rushing to the aid of white girls in trouble.
I just don't see how anyone can justify the war on marijuana anywhere in the country.
The evidence is in: The expensive war ruins lives with no hope of stemming use or supply. Random, mostly poor and minority people are violated (vaginally and otherwise), charged and stuck in jails when its use is widespread and even legal in many places. And, it has and continues to create a military-style wing of local law enforcement that makes a mockery of "serve and protect" with every no-knock raid on American citizens in the middle of the night just to pull a few plants out of the ground.
Jake Ellison can be reached at 206-448-8334 or firstname.lastname@example.com. Follow Jake on Twitter at twitter.com/Jake_News. Also, swing by and *LIKE* his page on Facebook. If Google Plus is your thing, check out our marijuana coverage here.


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In a concerted effort to keep our Rural Communities informed about events and information important to your town and rural communities in general, we are sharing events and conference information via our social media venues. Below is an important conference as well as a FREE webinar that will air on Aug. 19th.
|In partnership with the National Rural Assembly, the National Congress of American Indian's Legislative and Policy Research Centers is hosting a Rural Advocacy 101 webinar on Wednesday, August 19 at 11:00am ET.You should consider joining us for this webinar if you plan to attend the 2015 National Rural Assembly's Advocacy Day on September 10.
During Advocacy Day we will:
Please join us for this exciting webinar opportunity, Wednesday, August 19 @11amET.
And if you haven't registered for the National Rural Assembly, you can do that here
Don't forget that August 18 is the deadline to reserve a hotel room at special rates. Scholarships will be available until the funds are exhausted.
Contact us:
Whitney Kimball Coe
SAVE THE DATE: 2015 National Rural Assembly, September 8-10, 2015


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Featured News - Current News - Archived News - News Categories
Grants awarded through National Endowment for the Arts
Congressman Brian Higgins, D-NY-26, announced six Western New York art and cultural organizations will receive federal grants through the National Endowment for the Arts (NEA) totaling $150,000.
"Western New York is home to a rich and diverse collection of cultural agencies, which contribute to the fabric of the community and our local economy," Higgins said. "This federal investment will allow for the expansion and enrichment of cultural offerings available to the public."
Below is a summary of the local awards:
•Squeaky Wheel Film & Media Art Center - $15,000 to support the Buffalo Youth Media Institute
•Buffalo Philharmonic Orchestra - $10,000 to support "An American Siddhartha" performance featuring collaboration between Lehrer Dance and the BPO
•CEPA Gallery - $15,000 toward expansion of the Partner Schools program
•Just Buffalo Literary Center - $70,000 to support Read ÷ Seed ÷ Write, a collaboration with Grassroots Gardens of Buffalo featuring a coming-together of literature and community gardening
•University at Buffalo Center for the Arts - $30,000 to support the "Wanderlust" exhibition featuring hands-on learning with visiting artists, public lectures and professional development for K-12 art teachers
•White Pine Press - $10,000 toward the promotion of books of poetry and prose
Local agencies received funding through the NEA's Art Works program, which "supports the creation of art that meets the highest standards of excellence, public engagement with diverse and excellent art, lifelong learning in the arts, and the strengthening of communities through the arts."
Nationwide, 970 grants totaling close to $26 million were awarded through the Art Works program.
Established by Congress in 1965, the NEA is the largest national funder of the arts in the U.S. On average, every dollar in NEA funding leverages another $9 in arts funding from other sources. Nationally, the nonprofit arts industry generates $135.2 billion annually in economic activity.


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A stereotype of a busy, sweaty and always tired manager, working "24 hours a day", without whom everything may fall apart is going to history. Contemporary manager is elegant, smiling, well-dressed and do not have to or even should not "work hard", likewise his subordinates. However, should behave and work in a deliberate and effective manner that is clever and intelligent.
Along with growing complexity of human labour, change of attitude and behavior of employees, and in the sense of responsibility for work results, an idea of people management has evolved. Approximately from the early 50s a conception of so-called scientific management consisting in that the manager was talking and the performer was listening was in force. However, a complexity of work was low at that time as well as the sense of the responsibility of workers for the results.
Between 1947 and 1970 the conception towards growing working complexity, when the manager was talking and listening to what the performer said to him, was used.
Since the beginning of the 70s, when the work complexity has began to be high and at the same time personal responsibility for its effects has increased the conception of management was popularized according to which information exchange between the manager and the performer was both way: the first one and the second one either asked and listened.
Contemporary management consists in achieving aims through other people.
Main management functions are:
- description of operational aims;
- making decisions;
- planning;
- organizing;
- actuating;
- work motivation;
- controlling;
Management also include:
- effective management of human resources and material means e.g. money, facilities, time, materials etc.;
- adapting the tasks to its performers;
- description and estimation of work;
- delegation of powers and responsibilities;
- advising and communication;
- problem solving and decision making;
- leadership, i.e. such motivational influence, that necessary tasks would be performed without commands.
Effective management is an ability to achieve goals. Effective management, control and human activity are measured by the achievement of earlier established goals.
Operational effectivity or profitableness is – relation of an expenditure to achieved results
The above definition is comparable with the definition of labour efficiency. In simplification:
- efficiency – means performing a given task (purposefulness of the task),
- effectiveness – means performing a given task well (result of performance).
In order to understand the difference between efficiency and effectiveness contrasting "hard-working" and "effectively-working" persons can be helpful. Nobody wants to work hard, though it has been a synonym of efficiency and effectiveness for years. Practically, it was the symbol of inefficiency and bad management of the whole system.
Experienced manager knows that an employee, especially a new one, is carefully observing his environment and tries to understand what is going on in the company and a given team, who is actually in charge, who and what requires and what are the chances of gaining better salary, "earn money on the side" etc.
A reasonable manager understands that his employees know about their work and the nearest environment more than their superiors. That is why they should be good listeners, inspire for further reflections, encourage to improvements and innovations. In that way managers gain partners not thoughtless performers. Below has been presented a typical record of employee's expectations towards new workplace and superior's behavior
Famous American consultant, the author of many books about management, P.F. Drucker, suggests the following rules for the effective manager:Effective manager carefully organises and control his own time as well as analyses his work pursuing to eliminate waste of time. Often, this is the beginning of new distribution of work, commissioning of powers by managers and dealing with key business on which there is usually lack of time.Manager's attention should be focused not on "what one is doing but on what has to be done". Fundamental success factor of every conscious manager is perceiving his job through results of the whole organisation.Tries to use his energy to support and enforce so-called "strong points" of one's own and employee's. Manager's attitude should indicate to the employees that the best work would be highly evaluated such as punctuality and accuracy etc. In this way a manager concentrates foremost on one's own and his employee's usefulness, not on weaknesses.Another rule of an effective management constitutes effort focusing on chosen activities – works in a particular time on one or several tasks. It should be decided which information, meetings and contacts should belong to the manager and which can be passed. Choose the most important tasks, consciously picking those related to the future not past. Solve problems which may occur tomorrow and thanks to such proceedings minimise the intensity of arising "today's" problems and difficulties.Do not ignore favourable circumstances for achieving goals and takes advantage of various opportunities that occur. There is a view that ability to perceive those opportunities is more significant than the ability to solve minor problems.Last from the chosen rules is the ability to take such attitude which enables the manager to take advantage of constant feedback from his employees in order to check the results of decisions and activities. Complying with rule of "open door" for employees, make use of information about results of one's own proceedings, whether they are favourable or not, enables quick decision making.Table below represents how management rules changed through years of managing evolution.
|What do we do here?
|Clear designation of goals in the company and team section
|What are the requirements?
What should I do?
What can I do?
|Clear definition of responsibilities and requirements
|Where (in a team) is my place?
|Sympathy, full description of a role and function
|What would be my salary if?
– I complete required task well
– I do not complete the task well
– What the penalty/reward would be?
|Motivating: feedback
Advantages and disadvantages
Following the rules
|What risk I bear while submitting my ideas and observations to the superior?
How am I treated in relation to other employees?
How am I getting along?
|Listen carefully
Encourage and support
Consistent compliance with the principle of equal treatment of all employees
Periodic evaluation, clarity of norms
|Acknowledged till now
|Required nowadays
|Know the rules
|Know the atmosphere, team and informal team moods, attitudes towards management, environment
|Know key outcome areas
|Know key, prevailing values of organizational culture in the company
|Assess work results not actions, reward according to the outcome
|Don't forget about needs of higher order eg, satisfaction, recognition, influence on others etc.
|Be concerned with the future
|Not only the future of company but also employees
|Attain good economic results
|Acceptance of the company's environment Live in harmony with the natural environment
|Comply with regulations and managerial ethics
|Acceptance of the company's environment Live in harmony with the natural environment
Personal emotions, treat others in common with reasonable actions
-learn to recognize private and other people feelings
-learn to control emotions
-learn to establish and maintain contacts with
other people


text:
This is the "official" announcement of the new weekly, staged serial,
"Drag411" hosted by Amazon Alexa, iTunes, Google Play Music, Spotify,
YouTube, this page, and any iPhone/Android app. beginning July 4th. I need you to select the theme song that sounds fun and best matches the description of the series. The words to the song will be added later. The music is from two different bands that create commercial and movie music along with jingles.
Every day Georgi Evans wakes up to pandemonium since his marriage to
Micky two years ago. Their quiet Tampa life with Noodle, their rescue
dog, changed the moment Georgi decided to head back to the stage as the
over-the-top drag queen, Wynter Storm.
Georgi never went out of his
way to watch drag shows and when he met Micky, had no idea that his new
husband was a female impersonator decades ago. Georgi hoped Micky's
itch to perform for a local breast cancer charity event would be a
onetime shot, but Wynter Storm became a brief local celebrity after a
video of Wynter Storm went viral on the internet, after she was arrested
for physically attacking a congressman with her red pumps.
Poor Georgi and Noodle, caught between the madness of Wynter and
Micky's oldest friend, Stephanie Silver, once herself, a prominent
pageant queen in the seventies and now a leading activist for
transgender rights. In episode one of the series, Georgi finds an ally
when a neighbor moves in next door in their gay neighborhood, a lesbian
bartender named Poom... and her twelve cats.
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text:
Udyr Build Guide by wolffsasquirrel
Not Updated For Current Season
This guide has not yet been updated for the current season. Please keep this in mind while reading. You can see the most recently updated guides on the browse guides page.
Thank You!
Your votes and comments encourage our guide authors to continue
creating helpful guides for the League of Legends community.
Udyr Build
Ability Sequence
Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
Chapter 1
Alright after a long while, I have returned to update my build. For now, this build will be focused on one them for Udyr, but it does just about everything.
Under Construction Always, due to Input and Updates!
Build One: Burning Phoenix, Shielding Turtle.
B1P1: Main Focus of the Build
B1P2: Masteries
B1P3: Summoner Spells
B1P4: Runes
B1P5: Weapons
B1P6: Execution
B1P7: Misc Information.
Burning Phoenix, Shielding Turtle
B1P1: Main Focus of the Build
This build as stated by its name, is going to Focus on Udyr's and , as well as his passive, .
Lets Look into the other Three Abilities real quick:
Activation: Udyr gains a temporary shield that absorbs 60/100/140/180/220 (+0.5) damage.
Persistent Effect: Udyr's attacks cannot crit, but he restores 12/14/16/18/20% of his damage as health and 9/10.5/12/13.5/15% of his damage as mana.
Activation: Udyr sends out pulsing waves of fire dealing 15/25/35 (+0.25) magic damage each second to nearby enemies for 5 seconds. In addition, Udyr's Ability Power is increased by 16/24/32 and his Attack Damage is increased by half of that amount.
Persistent Effect: Every third attack, Udyr engulfs enemies in front of him in flame, dealing 40/80/120 (+0.25) magic damage.
Udyr's Passive ability: Entering a stance grants Udyr 10% attack speed and 3% dodge for 5 seconds. This effect can stack up to a maximum of three times = 30% attack speed and 9% dodge.
B1P2: Masteries
I have chosen this particular set of Masteries for one reason: The Perfect Jungle. Now I must say that in my opinion the perfect jungle consists of a fast, and reliable jungle.
Fast: Along with the Runes you will start with about 51 Ability Power, meaning that Phoenix Stance will eat through the camps.
Reliable: With the dodge, armor and magic resist you will be at a higher health capacity when finishing the jungle helping secure those first bloods and ganks.
B2P3: Summoner Spells
Seeing as how this Build is focused on Phoenix, which is great for Burning down those Camps, I grabbed with the Mastery it gives an extra 11 Ability Power, while also helping take the Blue Golem down extremely fast.
As always for a Junlger they love some for those quick/guaranteed kills with a little gold on the side..
B2P4: Runes
The Runes I chose for this build are an easy choice.
: More Ability Power for a faster Jungle.
: Faster attacks mean more On Hit Effects from Phoenix and more Health/Mana from Turtle, as well as More frequent procs from Wriggle's Lantern..
: Again, Faster Attacks mean more Phoenix, Turtle and Wriggles Love.
: Again, more Ability Power for that fast Phoenix Jungle.
B2P5: Weapons
The Items:
: A must have for a Jungler, don't question it.
: Armor, Dodge, and Movement a great item for any Udyr.
: Health/5, Mana/5 and Tenacity a great pick up as it allows for you to get a better set of boots.
: Great Magic Resist, Health/5 and a Speed bonus can't do much better for this build.
: Ability Power, Magic Resist and Magic Pen for everyone near you another staple item on this build.
: Health, Ability Power, and Phoenix AoE/On Hit Effect slowing enemies and champions down <3.
B2P6: Execution
Jungle: Currently starting at Golems, Wraith, Wolves, Blue Golem, Red Lizard, Golem Gank bottom, Wraiths aid mid, Wolves, Gank Top, go back and buy normally able to get Wriggle's and Boots, or at least Razor, Boots and a few pots. Then its back to Jungle, where you basically do the same path again, or you could just do Blue, Wolves, Wraiths, Red, Golem, Gank Bottom, Dragon, Mid, Top then back or if you didn't get any kills/ganks just return to your jungle..
B2P7: Misc Info
This Build is always up for input and ideas so please leave those comments. (Execution and Misc will come soon!)


text:
Refined, intelligent, animated, cultured
Voice Description
Narration & presentations - clear, cultured, intelligent, lively and interesting, confidence inspiring
Commercials & Promos - exciting, attractive, animated
Children's Narrative specialism - interesting characters, warm, dramatic and entertaining
Voice Genders and "Ages" I Can Perform
• Young Adult Female
• Middle Age Female
Language(s) of Which I Am a Native Speaker:
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• Spanish - Castilian (from Spain)
I Offer my Services for these Recording Purposes
• Commercials
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• Training, business presentations, sales, and web sites
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Jobs I Am Willing to Take (Union-wise)
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My Union Affiliations and Memberships
My Recording and Delivery Capabilities
• I can record and then deliver the audio files via Email
• I can record and then upload the audio files via FTP
• I can record and then deliver the files by regular mail
Pre-, Post- and Production Services I Offer
• I offer copywriting services
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• I can deliver edited and finished voice tracks
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My Home Base
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Accents, Impersonations, Characters and Dialects
Posh, librarian, cultured, Children's characters, French, Spanish,
My Voice Experience
We have provided VoiceOver work for language training and corporate videos as well as numerous other studio and location recordings through to masters. In addition, our artists have long experience in presentation and reading out loud, particularly with children's literature.
Results are guaranteed to delight you.
My Training
Significant acting experience, speeches and presentations, plus extensive copy-writing experience and 10 yr of experience in children's book publishing.
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Shure SM58
Rode NT5
Behringer C5
Tascam DR40 built-in condensers
Rode NT1-A
Pre-amp / Audio Interface
Digidesign MBox 2 Pro
Mac Pro OSX with:
Pro Tools 10 Native
Various additional plug-ins including Wave Arts MR Noise
Final Cut Pro
Blackmagic Intensity Pro video capture card
Izotope RX Audio Processing
Yamaha NS10 monitors, driven by Musical Fidelity Typhoon Power Amp
Mission HiFi speakers, driven by AudioLab 8000 Amp
Various consumer sound systems - mono & stereo - for testing
Plus, VHS players, Linn turntable, custom headphone and phono pre-amps, cassette deck, cd player, Fender Strat, Digidesign 11 rack guitar processor, Peavey Classic 50 Guitar Amp, Yamaha AN1X analogue keyboard, electric piano, acoustic drum kit, vibraphone, glockenspiel, various other mics, stands, cables etc.
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Unknown - Click here to ask Sian Hardy
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Sian Hardy was last active on Voice123 more than 365 days ago, OR may not be receiving our email messages.
Sian Hardy does not appear to be an active participant of the Voice123 marketplace at this time. Sian Hardy was last active on Voice123 more than 365 days ago, OR may not be receiving our email messages.


text:
The Beatles at Shea Stadium in 1965. Goodbye Shea, lots of good memories.
When I was younger, so much younger than today,
I never needed anybody's help in anyway.
But now these days are gone, I'm not so self assured,
Now I find I've changed my mind, I've opened up the doors.


text:
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text: These days, most automobile windows can be raised or lowered using buttons near the seats or on the inside of the doors. Different manufacturers of cars follow different methods of using the two buttons, either to raise or lower the glass using one single press or having to hold down the buttons. The motor which drives the glass up or down has multiple magnets or a multi-pole ring magnet fitted to it that actuates the reed sensor fitted near it and this gives feedback to the micro-processor regarding the actual position of the glass. The number of pulses that the reed sensor gives out for lowering or raising the glass completely is always the same and this is used to stop the motor when the glass reaches the top of the bottom. The feedback by the reed sensors to the microprocessor also helps check if there is an obstruction when the glass is being raised as the time between the pulses is being constantly monitored. The reed sensors work to raise and lower the glass and also as a safety device. Any of our SMD or PCB mountable reed sensors or wired Magnetic sensors cab be used for this application.


text:
Last month, a friend posed the following question:
Many people responded, with the most common advice being to apologize, but also to remember that other people's burdens are ultimately not about you. In other words, you can't fix what you didn't (and can't) cause.
My response was too big for a single screen shot (previous lines cut for privacy):
The last time Facebook created a blog topic, the post was my answer. This time, my friend specifically requested me to expand my reply:
With her vote of confidence, I attempt to do so now….
What my response didn't mention was that I described how I handle all conflicts, not just those in which people blame me for their unhappiness. I strive to confront conflict with the same mindfulness, respect, and honesty, regardless of who or what precipitated the situation.
I learned this wisdom several years ago, when the owner of a yoga studio (and my boss) confronted me about reports that I had encouraged students to attend classes at a competing studio, where I also taught classes. I had not done so, but my denials sounded hollow to him. Even when I asked how he could believe the ludicrous rationale of encouraging students not to support his studio, where I earned income, he refused to consider that the stories could be rumors.
Fortunately, my intuition recognized not to accept projections from people who were delusional about my integrity. I saw clearly that another person or other people blamed me, to some degree, for their lack, for their unhappiness or frustration. Though I never confronted those who accused me, I think jealousy motivated their actions. My classes were among the most successful at the studio, despite the one on Friday night being an unlikely time for high turnout.
However, the dynamic between me and the owner, and thus my job, never recovered from the false gossip. Though I held myself accountable and subsequently monitored my words even more carefully, he remained attached to his perception.
Within a few months, I was fired. Not surprisingly, my abrupt departure shocked my longtime students, particularly when it was framed as my own choice—by the owner and replacement teacher who lied to them. But as any politician who's had an affair knows, the truth will always surface. Eventually, my former students learned of the untruths.
Meanwhile, I had more important matters to which I had to attend—namely, not being steamrolled by resentment and anger. I was devastated at being fired. I had been working since age 14, the youngest legal age I could have a W-2 job, and I had never been less than a model employee. At the time I was in my mid-twenties, naively believing that being fired proved I was a failure.
Moreover, I had first begun practicing asana at this studio; it was the first place I ever taught any kind of yoga. I had done extra work for the owner, such as publicity, for free or very cheaply. The betrayal from someone I trusted bothered me even more than being fired. I struggled with the constant temptation to contact all my past students and tell them my side. Probably for the best that this conflict occurred pre-Facebook, when that task would have been easy, instead of so daunting that I did not do it.
Instead, I focused on how to handle the situation as constructively as possible:
~ I took responsibility for myself. When the owner first confronted me about the rumors, I acknowledged the possibility that my words could have been misconstrued. Inevitably, students asked what I knew about other studios and teachers. I analyzed my past conversations, considered if something I considered harmless had in fact misled someone to report something valid. And I apologized to the owner if in fact my comments—always delicate and diplomatic—to those queries was somehow taken as disloyal to the studio. I even asked teachers at others studios I supposedly recommended if anyone attended their classes because of my recommendation. (Not at all.)
~ In this process, I determined that I had not, to the fullest understanding from myself and others, behaved inappropriately. But after being fired, as I remained angry and resentful, I realized that I had to detach myself from needing those who had treated me so poorly to feel any remorse. Highly unlikely. Furthermore, I had to detach from needing an apology. Even more unlikely. They were never going to apologize.
~ I considered my contribution. Not just in terms of arousing jealousy, but how my actions may have worsened the situation. At first, I did not argue about the legitimacy of the claims against me; I didn't want to seem overly argumentative. But perhaps in doing so, I legitimized the rumors. Later, I told the owner that I thought people were lying to him, but by then my word was too damaged. I don't know whether a different response would have made a difference. Not that I care—more important that I consider my fullest potential participation in a conflict. Certainly in other instances my own actions have definitively affected the situation.
Since that virtual conversation, I have mostly been thinking about how my views of conflict have changed. As a child, I was conditioned to consider fairness as most important—for all parties to feel satisfied with the resolution. As an adult, I recognize that many people are not concerned with justice or integrity. And as if everyone agrees on a single definition of fairness!
Though it might seem counterintuitive, sometimes disregarding the feelings of others is the best option. I find that perspective much more empowering, actually. Some people will never forgive my mistakes, regardless of how much I try to atone. Other times, people will never atone for their wrongdoings.
One of the many, many lessons Eastern philosophies have taught me is that needing or wanting something (such as fairness) simply maintains attachment, which prolongs my own dis-ease. The people who "owe" me apologies—those people are least likely to do so. However, so what? So what. I saw how unempowered I was by craving something that others would never provide. I realized that I was blocking my own recovery from the situation—that I did not actually need what I wanted so badly. Nor do I want to depend on the actions of others to liberate me. When I confront conflict with full honesty and without attachment, I can be at peace with my own integrity and actions, rather than cling to past behaviors and mistakes. Consequently, reconciliation for mySelf is always possible.
∞ Special thanks to the beautifully grounded Katy Jo Schroer for starting this conversation and affirming my response.


text:
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Vendor: Microsoft
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Exam Name: Microsoft Project 2010, Managing Projects
Exam Code: 70-178
Total Questions: 65 Q&As
Last Updated: Aug 15, 2018
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In the meantime, please visit one of our stockists:
West Elm Albany, Stuyvesant Plaza Albany, NY
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text:
Gillian Murphy in The Dream. Photo: Gene Schiavone.
© Copyright 2018 Ballet Theatre Foundation, Inc.American Ballet Theatre and ABT are registered trademarks of Ballet Theatre Foundation, Inc.All rights reserved.
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Those listed below provide outstanding support and commitment to American Ballet Theatre as Chairman's Council Members; we offer them our profound thanks.
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