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The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain.
Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors.
A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] ptrend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] ptrend = 0.96 for ER-PR- tumors; Phet = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (phet = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk.
Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.
Keywords:ER-receptor; PR-receptor; Reproductive factors; Risk factors; Menopause; Parity; Oral contraceptive; Breast cancer
Breast cancer is a complex and heterogeneous disease with a variety of histo-pathological and molecular subtypes with diverse clinical outcomes and relationships with established risk factors [1-3]. The major sub-classification of clinical breast tumors is based on the detection of estrogen (ER) and progesterone (PR) receptors and guides targeted therapies and provides important prognostic information [4]. The presence or absence of hormone receptors, along with human epidermal growth factor-2 (HER2) also broadly correspond to more detailed molecular subclassification of breast tumors, as determined by microarray-based gene expression profiling coupled to hierarchical clustering analyses [5-7]. In addition to the clinical use of ER and PR, epidemiological data indicate that the association of reproductive history with breast cancer differs by the expression of ER and PR receptors [2].
Factors that influence the lifetime cumulative exposure to hormones during reproductive life, such as the age at menarche, age at first child-birth, time between age at menarche and first child birth, number of children, use of oral contraceptives (OC) and breastfeeding, have been suggested to be associated with risk of hormone receptor (HR)-positive malignancies (ER-positive or joint ER+PR+)[2,8-11]. However, distinct risk factors for HR-negative (ER-negative, or joint ER-PR) cancer are debated [2,3,8,12] and the etiologies of ER+PR+ and ER-PR- tumors remain unclear.
The incidence of HR-negative disease drops remarkably after menopause [13] suggesting that ovarian derived sex steroid hormones do have an impact on HR-negative tumors and recent studies are starting to show risk associations of reproductive factors with HR-negative malignancies [2,3]. In fact, opposite risk associations between ER-PR- and ER+PR+ tumors have been observed with parity [11,14], age at first pregnancy [9] and breastfeeding[11]. Nonetheless, due to the rarity and heterogeneous nature of HR-negative breast tumors, epidemiological studies have been hindered by small sample sizes resulting in inconsistent risk associations between reproductive factors and HR-negative disease [8,11,15,16].
The incidence of HR-negative disease drops remarkably after menopause [13] suggesting that ovarian derived sex steroid hormones do have an impact on HR-negative tumors and recent studies are starting to show risk associations of reproductive factors with HR-negative malignancies [2,3]. In fact, opposite risk associations between ER-PR- and ER+PR+ tumors have been observed with parity [11,14], age at first pregnancy [9] and breastfeeding [11]. Nonetheless, due to the rarity and heterogeneous nature of HR-negative breast tumors, epidemiological studies have been hindered by small sample sizes resulting in inconsistent risk associations between reproductive factors and HR-negative disease [3,8,14,15].
The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multi-center prospective cohort study designed to investigate the relationships between diet, nutrition and metabolic factors and cancer, consisting of approximately 360,000 women and 150,000 men aged mostly between 25–70 years [16,17]. All participants were enrolled between 1992 and 2000 and came from 23 regional and national research centers located in 10 western European countries: Denmark, France, Italy, Germany, Greece Norway, Spain, Sweden, The Netherlands and the United Kingdom. Extensive details about the standardized procedures for recruitment, measuring baseline anthropometry, questionnaires on current habitual diet, reproductive and menstrual history, exogenous hormone use [OC and hormone replacement therapy (HRT) use], medical history, lifetime smoking and alcohol consumption history, occupation, level of education and physical activity and biological sample collection at study centers are given elsewhere [16,17]. All subjects gave written informed consent. The Internal Review Boards of the International Agency for Research on Cancer and the local ethics committees in participating countries approved the analyses based on EPIC participants.
Study participants
Of the approximately 360,000 female participants in EPIC, women were excluded a priori if they had a history of cancer prior to recruitment or were missing a diagnosis or censoring date, thus leaving 345,153 participants. At the time of this analysis, three EPIC study centers, (Granada, Murcia and Malmo), did not provide any information on breast tumor hormone receptor status and therefore were excluded from this analysis (n = 26,091). Women were further excluded if they were missing questionnaire data (n = 526) or were missing data on age at menarche, age at menopause, age at first full-term birth, ever use of OCs, number of full-term births, age at last full-term childbirth and duration of breastfeeding (n = 7,439). This left a total of 311,097 women with 9,456 first primary invasive breast cancer cases from 10 countries for the present analysis.
Questionnaire data and classification of reproductive variables
The details of standardized procedures for collecting baseline information on the age at first and last menstruation, parity, breastfeeding, exogenous hormone use, and hysterectomy from the general lifestyle questionnaire has been previously reported [17,18]. Briefly, in Greece, Italy, the Netherlands, Sweden and the United Kingdom, age at menarche was asked in years. In the other countries, age at menarche was asked in defined categories (≤8, 9, 10,…, 18, 19 or >19 years). The number of full-term pregnancies (defined as the sum of all live and stillborn children born) and spontaneous or induced abortions were also collected at baseline, together with the ages of the first three and last deliveries and the ages at first and last induced or spontaneous abortions and stillbirths. Except for Norway and the Swedish center Umeå, where information about multiple pregnancies was available, the number of pregnancies is overestimated as multiple pregnancies were counted as different pregnancies. The length of time between menarche and age at first pregnancy was estimated among women who had menarche between the ages of 8 and 20 years (time between menarche and first full-term birth = age at first full-term birth – age at menarche).
Women were considered postmenopausal at recruitment if they had had no menstrual cycles in the last 12 months, were older than 55 years (if the menstrual cycle history was missing), or had a bilateral oophorectomy. Women who were aged 46–55 years and had incomplete or were missing questionnaire data on menstrual history were classified with a peri/-or of unknown menopausal status. Women were deemed premenopausal if they reported regular menstrual cycles in the last 12 months or if they were younger than 46 years of age (if the menstrual cycle history was missing).
The details of standardized procedures for measuring height and weight at EPIC study centers has also been previously reported [19]. In most countries, height, weight and waist and hip circumferences were measured to the nearest centimeter and kilogram, in light clothing, according to standardized protocols. In Norway, Umeå and a large proportion from France, subjects' height and weight were measured and self-reported by the cohort participants themselves, following detailed instructions [17,19]. For subjects that had neither self-reported nor measured weight or height data, the center-, age- and gender-specific average weight and height values were imputed for anthropometry variables used for adjustment purposes only. A sensitivity analysis that restricted the adjusted variables to those without imputation showed similar results to those presented (data not shown).
Prospective ascertainment of breast cancer cases and the coding of receptor status
In all countries (except for France, Germany and Greece) incident breast cancer cases were identified using record linkage with cancer and pathology registries. In France, Germany and Greece, cancer occurrence was prospectively ascertained through linkage with health insurance records and regular direct contact with participants and their next of kin, and all reported breast cancer cases were then systematically verified against clinical and pathological records. Mortality data were coded according to the 10th Revision of the International Statistical Classification of Diseases, Injuries, and Causes of Death (ICD-10), and cancer incidence data were coded according to the International Classification of Diseases for Oncology (ICD-O-2). Invasive (primary, malignant) breast cancer cases were classified as per the International Classification of Diseases for Oncology (Topography C50), second revision (ICD-O-2). Breast tumor receptor status was standardized across EPIC centers using the following criteria for a positive expression: ≥10% cells stained, any 'plus-system' description, ≥20 fmol/mg, an Allred score of ≥3, an IRS ≥2, or an H-score ≥10 [20].
Vital status was collected from regional or national mortality registries. The last updates of endpoint data for cancer incidence and vital status were between 2005 and 2010, depending on the center. Women were considered at risk from the time of recruitment until breast cancer diagnosis or censoring (age at death, loss to follow up, end of follow up, or diagnosis of other cancer) respectively. A total of 7,095 breast cancer cases had information on ER status (5,723 ER-positive, 1,372 ER-negative); of which, 5,843 had further information on PR status (3,567 ER+PR+, 1,078 ER+PR-, 200 ER-PR+, 998 ER-PR-).
Statistical analysis
Associations between reproductive factors and the risk of breast cancer subtype were evaluated using Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Breast cancer subtypes were defined as jointly classified ER+PR+ or ER-PR- breast tumors. Results for ER-positive versus ER-negative (ignoring PR status); and PR-positive versus PR-negative (ignoring ER status) were generally similar to the jointly defined ERPR breast cancer subtypes and have been included in Additional file 1: Table S1. Results for breast tumors with discordant ER and PR status and unknown ER and/or PR status have been reported in Additional file 2: Table S2. All analyses were stratified by age at recruitment in one-year categories and by study center, to prevent violations of the proportional-hazard assumption. Trend tests across levels of exposure categories were performed on the continuous categorical variables entered as ordered, quantitative variables into the models.
Additional file 1: Table S1. Reproductive factors and risk of ER-positive vs. ER-negative and PR-positive vs. PR-negative breast cancer in all women.
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Additional file 2: Table S2. Reproductive factors and risk of discordant breast cancer subtypes in all women.
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Age at menarche was categorized as ≤12, 13–14 and ≥15 years and time between menarche and first full-term childbirth as <10 and ≥10 years. Parity related variables were divided into the following categories ever vs. never, number of full-term pregnancies (1, 2, ≥3), age at first full-term childbirth as ≤19, 20–24, 25-29,30-34, ≥35 years, age at last full-term childbirth since recruitment as ≤24, 25–29, 30-34, ≥35 years and time since last child birth as ≤20 and >20 years. Breastfeeding was categorized as ever versus never, and ≤1 month, 2-3, 4–6, 7–12, 13–17 and ≥18 months for total cumulative duration of breastfeeding. Dichotomized categories of ever vs. never having had a spontaneous or induced abortion, ever vs. never OC use, and current versus not currently using OCs (at baseline) also were analyzed. The duration of OC use was categorized into ≤1, 2–4, 5–9, and ≥10 years. Age at menopause was divided into the categories ≤48, 49–50, 51–54 and ≥55 years.
A basic model stratified by age and center and a multivariable model further adjusted for body mass index (BMI kg/m2, as a continuous variable), height (as a continuous variable), menopausal status at enrolment (premenopausal, peri-/unknown menopausal, postmenopausal [natural and surgical menopause], HRT use (premenopausal, ever use, never use and missing in postmenopausal women only), smoking status (current, former, never, missing), baseline alcohol consumption (non-consumers, 0.1–6 g/day, 6-12 g/day, 12-24 g/day, 24-60 g/day and greater than 60 g/day, missing), physical activity (Cambridge Index: active, moderately active, moderately inactive and inactive, missing [21]), education level (none, primary school, technical/professional school, secondary school, longer education including university degree, missing) were assessed. Missing values (generally <2%) were accounted for by creating an extra category in each covariate.
To avoid collinearity when studying the joint effect of the number of full-term pregnancies, age at first and last full-term childbirth and time since last childbirth, we used the approach described by Heuch et al.[22]. In analyses including age at last full-term childbirth and time since last childbirth in an age adjusted model, the general age effect was represented by the age effect among nulliparous women. We assigned constant values for age at full-term childbirth and time since last full-term childbirth (corresponding to the reference categories) to nulliparous women, and indicator variables were introduced in the model to ensure that the risk estimates reflected effects in parous women only.
Differences in risk estimates of a given factor and across breast cancer subtypes were analyzed using the data augmentation method as described by Lunn and McNeil, using a likelihood ratio test to compare the model with and without interaction terms between the exposure of interest and breast cancer subtype [23]. Women were considered at risk of a given breast cancer subtype until they were diagnosed with a different competing breast cancer subtype or were diagnosed with breast cancer and the receptor status information was missing. These women were censored at the time of occurrence of the competing breast cancer subtype [23]. To assess whether breast cancer subtype reproductive risk factors changed across women after menopause, left and/or right side censoring was used to count person years within defined age periods <50 years, and ≥50 years. As no differences were observed between risk estimates of reproductive risk factors and breast cancer subtype risk across the age-bands we report results for all women combined. A sensitivity analysis restricting to cases with any indication of an ER and PR expression versus a complete absence of ER and PR expression (0% cells stained, a "-" description (i.e. a negative/minus symbol description), 0 fmol/mg, an Allred score of 0, an IRS = 0, or an H-score = 0) was also performed. Heterogeneity in the risk associations between subgroups by age at diagnosis (<50 vs. ≥50 years), OC use, center, median BMI, age at first pregnancy and ever having breastfed were also examined using the Cochran's Q statistic. A previous analysis on postmenopausal HRT use has been reported in the EPIC cohort, therefore HRT use as a predictor of breast cancer risk by HR status was not included in this analysis [24]. All statistical analyses were performed using the SAS software package, version 9.2 (SAS Institute, Cary, NC).
A total cohort of 311,097 women was followed for a sum of 3,346,356 person years. Women were recruited into the EPIC study at the median age of 51.1 years (Table 1). At the time of recruitment, 46.5% of the women were postmenopausal and the median age of menopause was 50.0 years. For parous women, the median age at first full-term birth across the EPIC centers was 24.0 and the median time between menarche and first child birth was 11.0 years. The median age at last full-term pregnancy was 29.0 years, and a median time of 22.9 years had passed since the last childbirth. Of the women who had breastfed (83.8%), the median time of breastfeeding was 6.0 months for all pregnancies.
Table 1. Baseline characteristics of 311,097 EPIC cohort participants
A statistically significant heterogeneity between the risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) tumors was observed for age at first full-term childbirth (Table 2). While Cox regression models showed no association with risk of ER-PR-malignancies, a first full-term childbirth after the age of 35 was associated with an increased risk of ER+PR+ tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] ptrend < 0.001, Phet = 0.03).
Table 2. Reproductive factors and risk of ER+PR+ and ER-PR- breast cancer in all women
For ER-PR- breast tumors, similar risk associations to ER+PR+ breast tumors were observed with increasing menarcheal age (≥15 vs. ≤ 13 years ER-PR- HR: 0.84 [95% CI 0.69-1.03], Ptrend =0.17; ER+PR+ HR: 0.76 [95% CI 0.68-0.85], Ptrend <0.001; Phet = 0.48), and among parous women, with longer time between menarche and first full-term childbirth (≥10 vs. < 10 years ER-PR- HR: 1.15 [95% CI 0.99-1.34], Ptrend =0.09; ER+PR+ HR: 1.22 [95% CI 1.12-1.33], Ptrend <0.001; Phet = 0.52). Although the relative risk estimates for ER-PR- breast malignancies were in a similar direction to the ER+PR+ tumors and no statistical heterogeneity between the breast cancer subtypes was observed, it should be noted that risk associations for ER-PR- malignancies were weaker in magnitude and failed to reach statistical significance.
Ever a full-term childbirth, number of childbirths, age- and time since last full-term childbirth were generally not associated with the risk of ER-PR- malignancies but were associated with ER+PR+ tumors, however no statistical heterogeneity between the breast cancer subtypes was observed. Moreover, OC use, duration of OC use, breast feeding, ever having an abortion (spontaneous or induced) and age at menopause showed no significant associations with either ER-PR- or ER+PR+ breast cancer.
When all of the pregnancy related variables were examined together in the same model, risk associations for an increased number of full-term births, and later first and last full-term childbirth with ER-PR- tumors appeared to slightly strengthen; however they remained statistically not significant and had wider confidence intervals (Table 3). When analyses were restricted to postmenopausal women, the risk estimates for a later age at first full-term childbirth with ER+PR+ tumors were stronger (≥35 vs. ≤19 years HR: 1.64 [95% CI 1.05-2.56] ptrend = 0.002) compared to the estimates for all the women combined (≥35 vs. ≤19 years HR: 1.30 [95% CI 0.95-1.79] ptrend = 0.02).
Table 3. A mutually adjusted model of pregnancy related variables and risk of ER+PR+ vs. ER-PR- breast cancer
Subgroup analyses showed no heterogeneity in most of the risk estimates of the reproductive variables for ER-PR- and ER+PR+ tumors (data not shown), with the exception of the duration of breastfeeding by age at first birth among parous women (Pheterogeneity = 0.002). Among women who had their first full-term childbirth before the age of 25, a longer duration of total breastfeeding showed an indication of a decreased risk association with ER+PR+ tumors (≥18vs. ≤ 1 month HR: 0.86 [95% CI 0.67-1.10], Ptrend = 0.01). In contrast, among women who had their first full-term childbirth after the age of 25, a longer cumulative duration of breastfeeding was associated with a particular increased risk of ER+PR+ tumors (≥18vs. ≤ 1 month HR: 1.50 [95% CI 1. 13–1.99], Ptrend = 0.005). For ER-PR- tumors, risk estimates in the similar direction to the ER+PR+ tumors were observed, however statistically not significant (first childbirth before the age of 25, ≥18vs. ≤ 1 month of breast feeding HR: 0.90 [95% CI 0.58-1.39], Ptrend = 0.89; first childbirth after the age of 25, ≥18vs. ≤ 1 month of breast feeding HR: 1.31 [95% CI 0.72-2.39], Ptrend = 0.41).
In the sensitivity analysis restricted to cases with any indication of a positive ER and PR expression versus a complete absence of ER and PR expression with reproductive factors showed similar patterns with risk of joint ER+PR+ and ER-PR- breast cancer subtypes (data not shown).
Our results showed a significantly heterogeneous risk association for age at first full-term pregnancy by receptor status of the tumor, where later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors. Menarcheal age and time period between menarche and first full-term childbirth showed suggestively similar risk associations with both ER-PR- and ER+PR+ tumors, however the risk estimates for ER-PR- tumors were generally weaker than for their ER+PR+ counterparts and only borderline significant. Although the heterogeneity between breast cancer subtypes was not statistically significant, other parity related factors (such as ever having a full-term childbirth, number of full-term childbirths, age- and time since last full-term childbirth) were associated only with ER+PR+ malignancies. Finally, the factors related to breastfeeding and OC use were generally not associated with HR-positive or HR-negative breast cancer risk.
Previous prospective studies investigating the association of reproductive factors with HR-positive breast cancer have shown relatively consistent inverse risk associations with increasing menarcheal age, ever having a full-term childbirth and particularly a full-term childbirth at an early age [3,9,14,25]. However, consensus on the associations with HR-negative tumors has not been reached because previous prospective studies have lacked sufficient sample sizes [3,9,26] and because of the heterogeneous nature of HR-negative subtypes [1]. A more recent study within the Women's Health Initiative [14] showed that ever having a full-term childbirth was associated with an increased risk of triple-negative breast cancer (ER-, PR- and HER2-) (n = 307) and the positive association was strengthened with an increasing number of full-term births. We were unable to confirm the positive risk association with ever having a full-term childbirth and increasing number of full-term pregnancies with HR-negative tumors, however we did not have information on triple negative tumors.
We observed for both ER-PR- and ER+PR+ tumors, similar risk associations with increasing menarcheal age and a longer time between menarche and first full-term childbirth. A recent study within the EPIC cohort previously reported on the association of menarche with both ER-PR- and ER+PR+ tumors within the context of childhood growth and earlier sexual maturity [27]. This study extends onto this study of menarche and growth and focuses on the time period between sexual maturity and first full-term pregnancy, thus illustrating the complex and entwined nature of endocrine-sensitive tumors with hormones during different life phases of growth, sexual maturity and reproduction. The inverse association of menarcheal age with increased breast cancer risk is thought to be resultant of a longer exposure to estrogens during a women's reproductive life [2] but may also reflect early pubertal years characterized by more intensive and increased exposure to estrogen [27,28]. Estrogens have been long established to have a late-stage growth promoting effect on estrogen sensitive tumors [29], however, evidence suggests that estrogens may also play an important role in earlier developmental stages of both HR-positive and -negative tumor types [30]. Mammary stem cells have been shown to respond to sex steroid hormones without having a clear expression of an ER or PR [31]. Further, the EPIC cohort, showed that pre-diagnostic levels of estrogens were associated with both HR-negative and HR-positive postmenopausal breast cancer [20]. The longer time between menarche and a women's first full-term childbirth would equate to a longer period of time with undifferentiated breast epithelial tissue and a shorter period of time that the breast is resistant to malignant transformation [26] and thus may have etiological importance in the formation of ER-PR- tumors as well.
We observed a significantly different risk association for a later age at first full-term childbirth with risk of HR-negative and HR-positive tumors, whereas the associations for parity related factors (such as ever having a full-term childbirth, age a last full-term childbirth and time since last full-term childbirth) appeared to aggregate around HR-positive tumors. The role of a pregnancy with the risk of breast cancer is thought to stem from two major avenues, firstly, hormonal changes before and after pregnancy and secondly [26], dramatic structural changes in the ductal system of the breast after pregnancy [26,32]. A full-term childbirth is associated with a long term post-pregnancy reduction in levels of circulating hormones [26]. Before a women's first pregnancy the breast contains a high proportion of undifferentiated ducts and associated alveolar buds. Complete differentiation only occurs during pregnancy and lactation via complex morphological, physiological, and molecular changes [32]. Terminally differentiated epithelial cells are more resistant to carcinogenic influences because of lower proliferation rates and longer DNA repair phases [26]. The distinct inverse risk association for an earlier age at first full-term childbirth with ER+PR+ disease could be due to a shorter exposure to higher levels of ovarian estrogens and a shorter period of time of undifferentiated breast epithelial cells.
Recent prospective studies have reported reduced risk associations with breastfeeding with both ER-PR- and ER+PR+ breast cancer [3,14]. In the current analysis, we also observed an inverse risk association for both ER-PR- and ER+PR+ malignancies with a longer cumulative duration of breastfeeding however, this was restricted to women who had an early full-term childbirth. In contrast to the recent studies, among women who had a later first full-term childbirth, an increased risk with ER-PR- and ER+PR+ breast tumors with a longer total duration of breastfeeding was observed. Breastfeeding is thought to protect a woman from developing breast cancer by increasing breast differentiation, postponing the return of the ovulatory menstrual cycle post-pregnancy, and/or changing the hormonal environment of the breast [9,26,32]. The inverse risk association of HR-negative and HR-positive tumors with breastfeeding coupled with a longer duration among young first time mothers could convey a similar protection. In addition, lactation at a younger age would also mean a shorter period of undifferentiated breast epithelial tissue [26].
OC use has been extensively studied by many epidemiological studies and most studies have found either no association or a moderate increased risk of overall breast cancer, particularly among very young women and recent OC users [26]. More recent case–control studies investigating the risk of HR-defined breast cancer have started showing relationships of OC use with HR-negative breast cancer [33-37]. In the current study, we were unable to confirm significant risk associations of ever OC use and a longer duration of OC use with HR-negative tumors. There were only a small number of baseline OC users within this analytical cohort, and unfortunately within the EPIC cohort, information of dose or type of OC used, date of last use and information on changes to OC use after baseline are not available. Similarly, the estrogens and progestins in oral contraceptives differ in type and concentration [37] and this could be hiding a risk association.
Major strengths of this study are its prospective design and large number of incident cases with receptor information. The large case numbers allowed an in-depth analysis of reproductive-related relative risks, describing risk associations among women of predominantly premenopausal and postmenopausal age. The large case numbers also enabled us to examine subgroup effects such as age at first birth, age at diagnosis, BMI and breastfeeding. To our knowledge, this analysis uses the largest number of incident cases of ER-PR- malignancies, although future prospective studies with a greater number of ER-PR- cases are necessary to characterize the associations, which are of substantially smaller magnitude when compared to their HR-positive counterparts. Our study does have its limitations. The determination of ER and PR status in breast tumors has become a standard part of breast cancer diagnosis and is used to predict endocrine therapy response [4]. While a number of studies have shown that the classification of the ER and PR in tumors is relatively robust [38,39], the accuracy of classifying an ER or PR-negative tumor remains controversial [40,41]. In the analysis that compared women with a complete absence of ER and PR expression to women with any indication of an ER and PR positive expression, ER-PR- risk estimates remained unchanged. Furthermore, proportions of ER and PR–negative tumors in the EPIC cohort are in line with previous reports [13,42]. In addition, the inclusion of PR provides an indication of a functional estrogen pathway [2] and thus a joint ER-PR- may be more reflective of a true ER-negative tumor. At the time of this study, additional information on HER2 expression to determine breast cancer subtypes into more detailed molecular sub-classifications could not be completed because of insufficient information on HER2. However, as the routine assessment of HER2 is relatively more recent than ER and PR assessment, future cohort analyses will be able to include HER2.
In conclusion, our study provides evidence that later age at first full-term childbirth is associated with an increased risk of ER+PR+ tumors but not with ER-PR- tumors. Moreover, age at menarche and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although associations were only borderline significant for HR-negative tumors. Further studies with more incident cases of ER-PR- tumors are needed to provide more precise risk estimation for reproductive factors with HR-negative tumors.
EPIC: European Prospective Investigation into Cancer and Nutrition; ER: Estrogen receptor; PR: Progesterone receptor; HR-positive: Hormone receptor-positive; HR-negative: Hormone receptor-negative; OC: Oral contraception; HR: Hazard ratio; 95% CI: 95% confidence interval; HER2: Human epidermal growth factor-2; BMI: Body mass index.
Competing interests
The authors declare they have no competing interests.
Authors' contributions
RR, AL, and RK contributed to the conception of the current analysis and all authors were involved in the design and acquisition of data from the EPIC cohort. RR, AL and RK contributed to the analysis and all authors contributed to the interpretation of the data. RR, KT, AL and RK drafted the manuscript and all authors revised the final draft critically for important critical content. All authors have given final approval of the version to be published.
We would like to thank Sabine Rohrmann, Jutta Schmitt and Jutta Kneisel for their assistance during the collection of hormone receptor status data, and we thank all the EPIC cohort participants for their contributions to data collection at baseline recruitment and during follow-up. Finally, the comments from the anonymous reviewers are also greatly acknowledged.
This work was (partly) supported by a grant from the German Research Foundation, Graduiertenkolleg 793: Epidemiology of communicable and chronic noncommunicable diseases and their interrelationships. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue contre le Cancer, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation and the Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RTICC 'Red Temática de Investigación Cooperativa en Cáncer (R06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, (United Kingdom).
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Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, Charrondiere UR, Hemon B, Casagrande C, Vignat J, Overvad K, Tjonneland A, Clavel-Chapelon F, Thiebaut A, Wahrendorf J, Boeing H, Trichopoulos D, Trichopoulou A, Vineis P, Palli D, Bueno-de-Mesquita HB, Peeters PH, Lund E, Engeset D, Gonzalez CA, Barricarte A, Berglund G, Hallmans G, Day NE, Key TJ, et al.: European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection.
Public Health Nutr 2002, 5(6B):1113-1124. PubMed Abstract | Publisher Full Text
Onland-Moret NC, Peeters PH, van Gils CH, Clavel-Chapelon F, Key T, Tjonneland A, Trichopoulou A, Kaaks R, Manjer J, Panico S, Palli D, Tehard B, Stoikidou M, Bueno-de-Mesquita HB, Boeing H, Overvad K, Lenner P, Quiros JR, Chirlaque MD, Miller AB, Khaw KT, Riboli E: Age at menarche in relation to adult height: the EPIC study.
Am J Epidemiol 2005, 162(7):623-632. PubMed Abstract | Publisher Full Text
Haftenberger M, Lahmann PH, Panico S, Gonzalez CA, Seidell JC, Boeing H, Giurdanella MC, Krogh V, Bueno-de-Mesquita HB, Peeters PH, Skeie G, Hjartaker A, Rodriguez M, Quiros JR, Berglund G, Janlert U, Khaw KT, Spencer EA, Overvad K, Tjonneland A, Clavel-Chapelon F, Tehard B, Miller AB, Klipstein-Grobusch K, Benetou V, Kiriazi G, Riboli E, Slimani N: Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Public Health Nutr 2002, 5(6B):1147-1162. PubMed Abstract | Publisher Full Text
James RE, Lukanova A, Dossus L, Becker S, Rinaldi S, Tjonneland A, Olsen A, Overvad K, Mesrine S, Engel P, Clavel-Chapelon F, Chang-Claude J, Vrieling A, Boeing H, Schutze M, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Krogh V, Panico S, Tumino R, Sacerdote C, Rodriguez L, Buckland G, Sanchez MJ, Amiano P, Ardanaz E, Bueno-de-Mesquita B, Ros MM, et al.: Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case–control study.
Cancer Prev Res 2011, 4(10):1626-1635. Publisher Full Text
Wareham NJ, Jakes RW, Rennie KL, Schuit J, Mitchell J, Hennings S, Day NE: Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Public Health Nutr 2003, 6(4):407-413. PubMed Abstract | Publisher Full Text
Heuch I, Albrektsen G, Kvale G: Modeling effects of age at and time since delivery on subsequent risk of cancer.
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Lunn M, McNeil D: Applying Cox regression to competing risks.
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Ritte R, Lukanova A, Berrino F, Dossus L, Tjonneland A, Olsen A, Overvad TF, Overvad K, Clavel-Chapelon F, Fournier A, Fagherazzi G, Rohrmann S, Teucher B, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Sieri S, Panico S, Tumino R, Vineis P, Quiros JR, Buckland G, Sanchez MJ, Amiano P, Chirlaque MD, Ardanaz E, Sund M, et al.: Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.
Breast Cancer Res 2012, 14(3):R76. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Setiawan VW, Monroe KR, Wilkens LR, Kolonel LN, Pike MC, Henderson BE: Breast cancer risk factors defined by estrogen and progesterone receptor status: the multiethnic cohort study.
Am J Epidemiol 2009, 169(10):1251-1259. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hankinson SE, Tamimi R, Hunter D: Breast cancer. In Textbook of Cancer Epidemiology. 2nd edition. Edited by Adami H, Hunter D, Trichopoulos D. Oxford: Oxford University Press; 2008:403-445.
Ritte R, Lukanova A, Tjonneland A, Olsen A, Overvad K, Mesrine S, Fagherazzi G, Dossus L, Teucher B, Steindorf K, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Grioni S, Mattiello A, Tumino R, Sacerdote C, Quiros JR, Buckland G, Molina-Montes E, Chirlaque MD, Ardanaz E, Amiano P, Bueno-de-Mesquita B, Van DF, Van Gils CH, Peeters PH, et al.: Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study.
Int J Cancer J Int du cancer 2013, 132(11):2619-2629. Publisher Full Text
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Dietel M, Lewis MA, Shapiro S: Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review.
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Allred DC, Brown P, Medina D: The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer.
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Asselin-Labat ML, Vaillant F, Sheridan JM, Pal B, Wu D, Simpson ER, Yasuda H, Smyth GK, Martin TJ, Lindeman GJ, Visvader JE: Control of mammary stem cell function by steroid hormone signalling.
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Althuis MD, Brogan DD, Coates RJ, Daling JR, Gammon MD, Malone KE, Schoenberg JB, Brinton LA: Breast cancers among very young premenopausal women (United States).
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Sweeney C, Giuliano AR, Baumgartner KB, Byers T, Herrick JS, Edwards SL, Slattery ML: Oral, injected and implanted contraceptives and breast cancer risk among U.S. Hispanic and non-Hispanic white women.
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Rosenberg L, Boggs DA, Wise LA, Adams-Campbell LL, Palmer JR: Oral contraceptive use and estrogen/progesterone receptor-negative breast cancer among African American women.
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Magne N, Toillon RA, Castadot P, Ramaioli A, Namer M: Different clinical impact of estradiol receptor determination according to the analytical method: a study on 1940 breast cancer patients over a period of 16 consecutive years.
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Chebil G, Bendahl PO, Idvall I, Ferno M: Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer–clinical associations and reasons for discrepancies.
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Cancer 2001, 92(1):37-45. PubMed Abstract | Publisher Full Text
Pre-publication history
The pre-publication history for this paper can be accessed here:


text:
Read Me Dead Chapter 1
I sit up in bed alert. I'm sweating, and my breathing comes in quick, short gasps. My long, thick curls stick to my neck, and I can still feel his large hands covering my mouth preventing me from breathing.
The outside lamp casts an orange glow through the blinds into the dark room. I stare at the shadows around me. I put my head in my hands and wait for the fear to pass, and I'm afraid. Afraid of what hides in the dark, what always hides in the dark. Secrets.
Matt, my twin brother, snores in the next room. The walls pop where the house settles in the night, and I jump. An owl hoots amidst the night songs of the crickets, and a twig snaps under the foot of someone outside. My heart rate accelerates, and its boom-boom-boom echoes loudly in my ears.
I want to listen closely to make sure that I'm not imagining the footsteps, but I can't hear anything other than my heart and heavy breathing. Matt's snoring breaks through the symphony of my fear playing in my ears. I take a deep breath and mentally count to ten. It's something Dr. Finnegan tells me will help when I'm upset. My breathing calms and so does my racing heart.
I strain my ears to hear. There are more footsteps. He's here. He's coming after me like he said he would.
I consider waking up my brother or even my aunt and uncle, but I don't know what I would tell them. The truth is out of the question, and I don't want to wake them at three in the morning when they have school and work in just a few hours. I pull my knees up to my chest and wrap my arms around them. I have to do something. I have to make sure that he doesn't kill me.
I grab my cell phone off the nightstand and dial a number I haven't called in almost a year.
"Hello," Christian answers.
"I need you."
"Alex?" He pauses. "What're you doing calling me in the middle of the night?" His speech is still somewhat slurred from sleep, but he sounds angry.
"I need you." I close my eyes to keep the tears at bay.
"I'm scared."
"Can't Matt help?"
"I don't know."
"This is crazy. We have school in a few hours."
"I think there's someone in the yard."
"What?" He sounds more alert now.
"I heard someone walking in the front yard."
"You sure it wasn't just an animal?"
He pauses, but I hear more movement on his end. I feel bad for waking him, but he's always been there for me.
"I'll be there soon," Christian says, and the phone beeps. I stare at it and listen to my surroundings. I sit still and hold my breath, eyes still on my phone. The footsteps are closer to my room now.
I slide out of bed, pull my curls back into a ponytail, walk to the door, and quietly open it. The hinges on the wooden door squeak, as I pull it open. I flinch hoping I haven't woken anyone. Matt snores in the room next to me, and no one comes rushing down the hallway to see what's going on. I manage to slide through the door without making any further noises. I feel my way along the hallway in the dark using my cell phone as a light to guide me until I'm past everyone's rooms.
As I wait at the door for Christian, I want to look out the peep hole, but I'm afraid of who I'll see. That's when it hits me. I just sent Christian to check and see if there's a murderer in my front yard.

subset: commoncrawl


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Toronto RHP Esmil Rogers (5-7, 4.47) goes against Boston LHP Jon Lester (14-8, 3.75) today at 7:10 p.m.
The Red Sox have a chance to clinch the AL East tonight with a win or a Tampa Bay Rays loss.
Shane Victorino, who was not in the lineup Thursday because of a jammed right thumb, was in the original lineup but has since been removed.
- Dustin Pedroia 2B
- Daniel Nava RF
- David Ortiz DH
- Mike Napoli 1B
- Mike Carp LF
- Jarrod Saltalamacchia C
- Will Middlebrooks 3B
- Stephen Drew SS
- Jackie Bradley Jr. CF


text:
Droidnaught is a procedurally generated first-person sci-fi dungeon crawler inspired by classics of the genre such as Captive, Hired Guns and Dungeon Master, combined with modern survival horror themes and roguelike elements.
You are not logged in, your comment will be anonymous unless you join the community today (totally free - or sign in with your social account on the right) which we encourage all contributors to do.
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Would you like to share your favorite recipes and kitchen secrets? Send them to us and we'll publish them for you! All you have to do is e-mail them to firstname.lastname@example.com and we'll do the rest. Credits will, of course, go to the sender of the recipe. We can also create a link to your blog or website, if you have any, for promotion. A few rules must be followed:
1. The recipe must be a traditional Filipino dish or a dish that can be prepared using local ingredients.
2. The recipe must be written in English. Please provide description and the place of origin.
3. The recipe may undergo an editing process when necessary.
4. The recipe may have been previously published in print (magazine, cookbooks, etc.), but not online. It must be an original work of the author/s. Publication must be cited. Plagiarism is not tolerated.
5. Images of the dish may be included.
6. The recipe is subject for posting approval.
7. All submitted recipes will be credited to their respective authors. The owner of this site does not have the rights to claim ownership of the submitted recipes. However, author's submission of recipes automatically gives the owner of this site the rights to publish them.
8. All published recipes may be removed from the site for any reason by the owner of this site or by the request of the sender.
9. Rules are subject to change without prior notice.
This is not a contest. This is just a way for us to exchange ideas and share recipes and meet great people online, hence, submission is voluntary. Consider this an online support group of lovers of Pinoy food. Haha!
So there you have it! If you have any questions, feel free to send us a message at email@example.com or go to this link.
§ 4 Responses to Share Your Recipes"
Life has no rewinds n forwards. It unfolds itself at its own pace. So never miss a chance to live today to make a beautiful story for tomorrow. Have a Nice Day.
A Smile Is The Lighting System Of The Face,
Cooling System Of Head And
Healing System Of Heart.
So Keep Smiling All Day.
Have A Nice Day!!!
Smooth roads never make good drivers..
Smooth sea never make good sailors..
Clear skies never make good pilots..
Problem free life never makes a strong & good person..
Have a tough, but winning day ahead….
Be strong enough to accept the challenges of life..
For guest post or articles, aside from recipes, can I also send you an article about Filipino foods. It can be awesome facts or trivias about it.


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Back to CIT 2009 Recordings
Dr. Harry E. Pence, SUNY College at Oneonta presented a session on "Teaching in the 21st Century" on Thursday afternoon, May 21, 2009. Dr. Pence is Professor of Chemistry at SUNY Oneonta. His presentation was broadcast live and recorded.
Broadcast and recording sponsored by Affinity Enterprises.
Sponsored by
Faculty Access to Computing Technologies (FACT) Committee - Faculty Council of Community Colleges (FCCC) - Center for Professional Development (CPD) - University Faculty Senate (UFS)


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- Infowars - http://www.infowars.com -
US Protest Slams Persisting Police Brutality Under NYPD's Stop-and-frisk Bid
Posted By Adan On February 25, 2013 @ 4:18 pm In Old Infowars Posts Style,Police State | Comments Disabled
Press TV
February 25, 2013
US protesters in the racially diverse Bronx section of New York City have held another rally against persisting police brutality and its controversial stop-and-frisk tactics that mainly targets minorities.
Angry Demonstrators from Bronx and across New York marched on Saturday afternoon in a "Stop the Cops" protest rally from the neighborhood to the Harlem section of the major city, predominantly populated by African American residents, who have been the prime target of New York Police Department's (NYPD) Stop-and-Frisk approach.
The NYPD's supposed "crime-fighting" tactic has come under widespread criticism as highly discriminatory, singling out mostly African American and Hispanic residents of the largest US city.
This is while merely 12 percent of those stopped and searched by NYPD forces under the Stop-and-Frisk policy have been found guilty of violating the law in some way, according to figures released by local rights groups.
The continuing enforcement of the policy by police officers has raised growing concerns over racial profiling.
The march comes nearly a year after the killing of 18-year-old Bronx resident Ramarley Graham, who was shot by NYPD officers in the bathroom of his own home while unarmed. At about the same time, another African American teenager, Trayvon Martin, was shot and killed in Florida by an armed guard.
Article printed from Infowars: http://www.infowars.com
URL to article: http://www.infowars.com/us-protest-slams-persisting-police-brutality-under-nypds-stop-and-frisk-bid/
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National Democratic Coalition on Tuesday said those who connived with the military to annul June 12, 1993, presidential election reportedly won by business mogul, Chief MKO Abiola, were still in government.
Chairman, NADECO, Rear Admiral Ndubuisi Kanu (retd.), stated this during the 19th anniversary of June 11, 1994 Epetedo Declaration by Abiola.
Kanu, in a speech entitled '19 Years After the Epetedo Declaration: Where is the Sovereign Power of the People?', said, "Many who connived with the clique in those debasing and disenfranchising years are in power today, even masquerading as champions of democracy.
"Such people include those who chaired Abiola's winning party, the Social Democratic Party, now today sitting atop party's board of trustees.
"Some reign at the pinnacle of the legislative arm of government in Abuja. There are numerous others in the arms of government and even among the progressives, who ought really to search their conscience, if the survival, well-being and progress of Nigeria is truly in their agenda."
He restated the call for a Sovereign National Conference, saying the conference remained the panacea for the country's socio-economic and political development.
He said the 1999 Constitution was imposed on Nigerians in utter negation of their sovereignty.
Another NADECO leader, Chief Ayo Opadokun, urged pro-democracy groups to do more to liberate the country.
He said, "We need to do more than we are doing. We need to get ourselves organised in our streets, wards and various levels and constitutionally engage those in power that have turned us into servitude.
"This is a country that exports what it does not have and imports what it has. Nigeria has oil, yet the leaders are importing oil for domestic use. Statistics available to me is that over 18 million graduates in Nigeria are jobless. This should not be if those in government could block wastage and eradicate corruption."
A lawyer, Fred Agbeyegbe, spoke on the need and modalities for an SNC, saying the conference was the business of Nigerians.
Also, Governor Abiola Ajimobi of Oyo State described the proscribed poll as a watershed in the annals of the country.
He said the supreme price paid by Abiola, could not be forgotten.
In a related development, the Osun State government has declared Wednesday (today) a public holiday in commemoration of the anniversary.
A statement by the state Commissioner for Information and Strategy, Chief Sunday Akere, on Tuesday, said symposia, rallies and a documentary on the life of Abiola would mark the event.
Meanwhile, Nobel Laureate, Prof. Wole Soyinka, has said May 29, which the Federal Government branded Democracy Day, lacks the credibility of the June 12 presidential election, won by Abiola.
Soyinka stated this in a statement on the 20th anniversary of the June 12 election on Tuesday.
He said, "We need to remind ourselves what June 12, 1993 represents. It is neither mere date, nor sentiment. It is simply – Human Spirit. What a futile undertaking it is then, when some individuals attempt to deny or crush it. Yet it was the power of this very spirit that brought such out of relegation or obscurity, even from the jaws of death, and bestowed upon them relevance and prominence.
"What June 12 possesses is exactly what May 29, or any other day, lacks. The former was a spirit of unified purpose, the latter simply an egotistical appropriation of the gift of the former. June 12 embodies unity of purpose, equity and justice, the manifestation of the sovereign will of a people. It remains forever a watershed of Nigerian history, no matter what the future holds.
"I urge you to try a simple experiment: narrate the story of May 29 to a child and watch his or her reaction. On that day – that child would concede – an individual was installed as a compromise president following a compromise election. So, what is new?"
Soyinka added, "Now move on to unfold the tapestry of June 12. Run your finger along its traceries of citizen resolve, upheavals, of individual and group heroisms, of sacrifices and martyrdoms, the timeless narrative of human resilience. Watch the difference in that child's responses. Yet, even the beneficiaries of that day persist in their futile effort to kill the date and supplant it with another. Why should we be surprised?
It is that unprincipled game of substitution that they have carried even to subsequent elections, substituting names of the rightful winners of elections with others who were never even in contention. "It is this same mental compulsion that moves them to attempt to rob even a calendar date of its significance, its history, its potential for character formation and sense of national formation – and transformation."


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Cordless Rotary Hammer Hilti's new rechargeable battery-powered rotary hammer (model TE 4-A18) has a high-efficiency motor and eccentric gearing that, combined with its exclusive warranted 18-volt CPC batteries, enables it to drill more holes in concrete per charge than any other cordless rotary hammer in its class, says the company. Features include a keyless chuck, variable-speed trigger, and drop-resistant housing. Two drilling modes, hammer-drilling and drilling only, add to the tool's versatility. Price: $599 with two batteries and charger. 800-363-4458. www.us.hilti.com.
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Find inspiration in hundreds of incredible photos, design ideas and tips from local professionals
Check out these standout spaces in detail and get the skinny on how they were designed
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"A New Relationship to Food: Invigorate Your Metabolism, Boost Your Energy & Start Losing 10lbs Today!"
With Katharine Pike & Liza Pitsirilos
Do you wake up feeling sluggish and your energy yo-yos throughout the day? Have you put on 5, 10 or even 25+ pounds and can't seem to lose the extra weight when you eat "right" and exercise? Are you sick and tired of food ruling your life and are you ready to change your relationship to it? Are you uninspired and irritable about your work and home environment because it's toxic leading you to higher levels of stress and poor health choices?
If you've answered "YES" to several of these questions and are Struggling to Make Clear Confident Decisions to change the quality of your life, then you don't want to miss this FREE Tele-Class
"A New Relationship to Food:Invigorate Your Metabolism, Boost Your Energy & Start Losing 10lbs Today!"
A FREE TELE-Class
with Katharine Pike & Liza Pitsirilos
Wednesday, October 23rd at 8:00pm EST
Get Ready to Fall in Love with Yourself Again, and Fall in Love with Your Food Again!
In this FREE Class You Will Learn: The #1 mistake you may be making when trying to lose weight that puts the brakes on your metabolism The see-saw effect: why most diets make you weigh more than when you started! The top 3 foods you need to start eating, so that you can boost your energy now Initial actions steps to dismantle stress and start losing weight this minute! Time is ticking and the holidays are quickly approaching.Family stress and food indulgences are creeping closer and closer. Let's jump-start your new relationship with food so you are lighter and brighter for the holidays! So what are you waiting for? Get on the Teleseminar Class and avoid ending upgaining another 10lbs over the holidays! Gasp!
Your Facilitators:
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White-eyes (Zosteropidae)
Black-capped Speirops (Speirops lugubris) - HBW 13, p. 485
Zostérops de Sao Tomé
German: Trauerbrillenvogel
Anteojitos de Santo Tomé
Other common names: Sao Tome Speirops
Taxonomy: Zosterops
lugubris Hartlaub, 1848, São Tomé.
Forms a superspecies with S. melanocephalus, and formerly considered conspecific, but morphologically and ecologically different; S. leucophoeus possibly belongs to same superspecies. Monotypic.
Distribution: Mountains of São Tomé I, in Gulf of Guinea.
- Least Concern Enlarge map
Videos1 video
Brief view in the rain Locality São Tomé and Principe
claude velter 8 November 2013 1 year ago 10 sec 3.7
Photos2 photos
adult perched
Locality São Tomé, São Tomé and Principe (Monotypic species)
Nik Borrow 14 August 2009 1 year ago 4.3
A bird perched in a bush
Locality Bom Sucesso Botanical Garden, São Tomé, São Tomé and Principe (Monotypic species)
Ian Fulton 29 July 2010 5 years ago 3.4
Sounds0 recordings
- No sound recordings available yet


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Great Plains Technology Center
Campus Locations
Lawton Campus
4500 W. Lee Blvd.
Lawton, Oklahoma 73505
(580) 355-6371
Tillman-Kiowa Campus
2001 E. Gladstone Ave.
Frederick, OK 73542-4600
Projects and Unique Attributes
Great Plains Technology Center (GPTC) is committed to developing sustainable world class partnerships. It is the career education institution and trainer of choice for Lawton's Goodyear Tire and Rubber Company plant, the world's most efficient tire manufacturing facility. This high caliber relationship is in its 34th year.
GPTC's commitment to partnering with every community in its district is exemplified by the professional firefighter training it provides to more than 30 volunteer and paid departments. The Lawton campus houses Comanche County and the City of Lawton's state-of-the art E-911 Emergency Response Center.
Oklahoma's annual wheat harvest kicks off each June in Tillman County. CASE IH Pro Harvest honored Great Plains Frederick (Tillman-Kiowa County) campus staff in 2012 for its 20 year partnership in hosting and providing safety training for this important event.
GPTC was selected as one of "Oklahoma's Best Places to Work" in 2012 by the Best Companies Group. GPTC celebrates its staff's commitment to students, clients and to each other as the driving force behind the selection.
District Population and Partner Schools
District population is 135,314 based on 2010 census data. School districts served include Big Pasture, Bishop, Cache, Chattanooga, Davidson, Elgin, Fletcher, Flower Mound, Frederick, Geronimo, Grandfield, Indiahoma, Lawton, Snyder, Sterling and Tipton.


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1951. USA. Charles Chaplin. 136 min.
Thursday, April 26, 2012, 1:00 p.m.
Theater 3 (The Celeste Bartos Theater), mezzanine, The Lewis B. and Dorothy Cullman Education and Research Building
1951. USA. Directed, written, produced, and music by Charles Chaplin. With Chaplin, Claire Bloom, Buster Keaton, Sydney Chaplin, Norman Lloyd. In perhaps the most auteurist of all films, Chaplin reflects on his life and career and gives what is quite possibly the most deeply felt performance in film history. 136 min.
In the Film exhibition An Auteurist History of Film
Ticketing policies for film screenings
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The Law Offices of F. Russell Wilson is a full-service immigration law firm located in San Rafael, California. We offer visa, green card and naturalization services to the entire north Bay Area, including Santa Rosa, Petaluma, Novato, Mill Valley, Sausalito, San Francisco, Oakland, Walnut Creek, Berkeley, Vallejo, Napa, Sonoma and Sacramento. We also have a long history of serving clients throughout Southern California, including communities in San Diego, Riverside, Orange and Los Angeles counties, in addition to clients throughout the United States and worldwide.
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Reviews, reviews, reviews...
FreakScore is a weighted average of all aggregated professional and user review scores.
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This product has a FreakScore of 8.5
out of 10 based on 745 scores.
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Troopers: Driver nearly doubles Taconic's 55-mph limit
10 Responses
If the State Police had ASSAULT RIFLES, they would have prevented this traffic violation.
See, the Pooper Troopers are right; LOL
This is why we have the State Police, not for ASSAULT RIFLES.
When you visit the East from more progressive and enlightened States west of New England it is very frustrating to find Age Old Iconic Speed Limits like one does in New England. To spend hours or days maintaining a speed of 70 mph via cruise control and then come on to something like the Taconic just creates anger and frustration.
Granted it is a big Money Maker as in being a 100 mile long Speed Trap with Troopers every 5 – 10 miles sneaking about, driving purposely painted and designed "Stealth Car's" and Police Uniforms designed to intimidate the citzens upon veiwing them…
You can't call it a "hidden tax" cause it is right out in the open, but basically that is what it is, another way to Tax you and knowing your frustation of having to drive 55 mph..it is all done on purpose by your Elected Officals and you have to wonder how many "courtesy" wave on's are routinely given and to who!
So again if you don't like it, well, who did you vote for who is allowing this to happen… 111 mph is a bit over the speed limit but I for one having driven the length and breath of this Country over a dozen times can honestly relate to this driver…And I know Truckers consider it drudgery and costs them time and money to have to drive in New England…So there is another reason businesses have left New England…more hidden taxation from your Elected Officals….
I've known at least two-hundred people who have been killed by cigarettes.
I've known at least that many people who have been killed by the bottle.
And yet I have never known another human being who died from too much grass.
I am not even aware of it happening in all recorded human history.
Can someone please explain to me why we still having this stupid conversation in the year 2010? It's embarrassing.
Tom Degan
Tom – too much grass may cause you to post a comment in the wrong thread
Obviously Tom doesn't watch the news,,,How many grass dealers are killed each year? 100 – 200? How many grass buyers trying to cheat the man are killed each year 100 – 200? How many 16 year old kids plow their Daddies car into a big tree each year who have ingested some grass..How many people have pulmonary diseases and are walking around with their little green bottles from ingesting to much grass…How many people make very bad financial and personal decisons because they were ingesting grass..How many kids have lung problems from the smoke in their houses. How many artist's paint "bad art" because they painted whatever while ingesting grass and then complain nobody understand their work?? (thousands) The list goes on and on…But according to Tom none of this happens..why? I wonder if Tom wrote his item while ingesting grass and is blinded by the smoke…
The person who wrote the headline needs a calculator.
Wow such comments. I totally agree with eddie S (#2). Everything he wrote is quite true. This state needs to modernize and it needs to stop stealing from it's citizens and visitors. Will the last one to leave NY please turn off the light……..
Keep up the great work NYSP. For every speeder you sit in wait for and catch, there is a violent crime being commited that is taking place because you are sitting in your car waiting for the easy take down. The criminal problems of our society aren't in the form of speeders. With that in mind, what is the real purpose of speed control? Revenue? Not that the NYSP would ever admit to that when they are getting their super new laser guns ( and assault rifles? )to keep us criminal speeders in line.
When it comes to driving, speed doesn't kill, but our authorities would like you to think so. It's a money thing.
Having regularly driven the Taconic parkway for a good share of my life, the suggestion of raising the speed limit on that highway is scary. Even with the more recent efforts to widen the highway in its most dangerous spots, that road was never designed for high speed driving, but rather slower scenic drives in the country (read The Power Broker for the back story on Robert Moses and the parkway construction). The lanes are narrow, and there are no shoulders. There have been lives lost on it in the past. Raising the speed limit would only increase the death toll.
And yes, I'm guilty of having sped on that highway, too. And I paid for it with a ticket. I have no excuse for being distracted and speeding on such a twisting road.
The Taconic is an enjoyable death trap, yet I think 55 is actually too low if that makes any sense. From the Sprain to at least I-84, I set the cruise (nervously) at 65 and still get passed in packs. If they added inner and outer shoulders to provide wiggle room, NYSDOT can whip out those never used 60 MPH signs.


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Some 2 percent of the Arabs of the West Bank and Gaza are Christians. Not so long ago they were roughly 15 percent of the Arab population. The rest are Muslims, all Sunnis. What explains the decline? Birth rates, of course. Christians are better educated than Muslims (all over the Middle East), and they know that if you want to raise a productive, truly loving, and educated family, you'd be wise to raise fewer children and give them all more attention.
The other reason that so many Christians have gradually abandoned Palestine is that their living among Muslims was a frightful experience. (Christians began decades back in deserting Iraq, too--at least, those who were not slaughtered.) Now, many Christian clergy have lined up against Israel, because they know that the Jews will not harm them. Moreover, they don't want to and have no reason to. The Christian authorities in the territories (and in Jerusalem) try to pacify the Muslims by joining the ugly chorus against Israel. Although they have been playing this appeasement game for nearly a century, it has done them no good.
Arab nationalism in places like Iraq, Syria, and Lebanon was at bottom a secular creation of Christians (and even Jews) as a tactic to ward off a politics of Muslim fanaticism. This started as far back as the middle of the nineteenth century. But, as we know from the history of these three countries, nationalism is no one's primary identification. Sectarian loyalty is. Nationalism came much later to Palestine, where the local Arabs were, in any case, politically backward. In any case, Palestine is a Christian idea. The first really important (also shoddy and romanticized) Palestinian book, The Arab Awakening, was written by an Anglican, George Antonius. Edward Said was an Anglican, and so were the heads of the ultra-Palestinian terrorist organizations. Yasir Arafat pretended to be a Palestinian nationalist. What he was truly was a militant Sunni in modern military garb. Certainly now, Palestinian nationalism, as you can tell just from reading the newspapers, is not exactly a healthy specimen. And its Muslim essence is apparent for all to see. That makes emerging Palestine more frightening to the Christians.
This week, two militant Muslim organizations in Gaza, the Huda Guidance Army and the Army of the Sword of the Right, threatened local Christians with mayhem. Seven churches have already been firebombed. All this in response to Pope Benedict. According to the Jerusalem Post, a group of Muslim clerics warned the Vicar of Christ that he'd have to convert to Islam if his life was to be spared. A leader of the 4,500 Christians in Gaza said that "many of them would like to leave the area out of fear for their lives." And then there would be none.
For all the violence against Christians in Palestine, the rage has been more extreme in other countries. (But this same Gazan clerical group has announced "a day of rage" for this coming Friday. Who knows what will occur then?) In any case, the controversy around the papal remarks will not be stilled quickly. Muslim countries are habituated to blaming the other for their degraded cultures. And now they have the world's most significant Christian in their sights. They won't let him go easily.
In a Los Angeles Times column yesterday, George Weigel added some understanding to the meaning of the controversy:
Can Islam be self-critical? Can its leaders condemn and marginalize its extremists, or are Muslims condemned to be held hostage to the passions of those who consider the murder of innocents to be pleasing to God? Can the West recover its commitment to reason and thus help support Islamic reformers? These are the large questions that Pope Benedict XVI has put on the world's agenda.
You can read the full article here.


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Jake Doyle scored 20 points for the East Mills boys basketball team in a 40-38 Corner Conference victory over Villisca on Friday.
Bolton hit 8-of-12 shots from the field, including 3-of-6 three pointers, to lead all scorers with 20.
Luke Schafer, Nathen Day and Jake Bolton added six points each.
Marshall Dolch led Villisca with 17 points and Timmy Myers added 13.
Treynor 59,
East Mills 44
The Glenwood Board of Education is looking into the idea of sharing a district superintendent, perhaps with the Malvern School District, as a cost-cutting solution to replace out-going Glenwood superintendent Dr. Stan Sibley, scheduled to retire on July 1.
More that 30 people showed up to hear the Glenwood Community School District lay out its plan for an Instructional Support Levy (ISL) at a public forum on Monday.
Whether that translates into the necessary votes for the ISL to pass, voters and the Glenwood School District will have to wait until the Feb. 2 special election.
Most first days on the job involve getting acquainted with your co-workers, adjusting to your new desk and figuring out how to use the copy machine.
You know, first day stuff.
Not new Glenwood Mayor Kim Clark.
No, Clark spent her first day on the job knee deep in financial paper work going over the city's mounting snow removal debt.
Two Malvern residents are facing drug-related charges following their arrests during the early-morning hours of Wednesday, Jan. 6.
As the result of information obtained during an on-going investigation, Mills County Sheriff's deputies served a search warrant at 609 Third Ave. in Malvern shortly after 3 a.m. During the search of the residence, deputies seized a substance believed to be methamphetamine with a total weight of over 5 grams, marijuana and two precursors believed to be pseudoephedrine and lithium. Both are commonly used in the production of methamphetamine.
With snow and blistering cold preventing the Glenwood basketball team from three days of practice, Ram coach Curt Schulte put his team through a rigorous 90-minute work out prior to their game with Red Oak on Saturday afternoon.
The jumpstart seemed to payoff as Glenwood rattled off 15 points in a row in the first quarter and led by as many as 29 in a 67-42 Hawkeye 10 Conference victory on Saturday.
Colin White earned a first place medal and Sam Jameson and Nate Harms both placed second for Glenwood in a second-place team finish at the Gary Christiansen Tournament at Winterset on Saturday.
"The guys did a great job today," said Glenwood coach Matt Dyer. "We were actually in the lead coming into the final round. Urbandale had a few more guys place higher than us and that's what cost us the lead. I am very proud of this team. It was a total team effort to place as high as we did."
As the investigation continues into a forgery scheme that bilked Operation Santa out of more than $11,000 the Glenwood non-profit that has spent more than a decade helping needy families buy Christmas gifts got a gift of its own last week.
The Mutual of Omaha Foundation has donated $10,000 to Operation Santa to cover the losses the group has suffered as a result of more than 220 forged $50 gift vouchers.
A resident of a Glenwood apartment complex that suffered $30,000 in damages in a Dec. 21 fire has been charged with first degree arson after allegedly setting the blaze.
Jarrett D. Dunn, 36, the resident of Unit 10 where the blaze ignited in a kitchen area of the former Chief Motel at 6 North Locust St., was arrested on Dec. 23 after a confrontation with police. Damages to the complex were mostly confined to Dunn's unit.
Glenwood letter carriers are asking customers for some help in clearing a path to their mailboxes. Unsafe conditions such as unshoveled snow, icy sidewalks and porches, or large amounts of snow blocking mailboxes can delay or even prevent mail delivery.
Copyright © 2015
The Opinion Tribune is your source for local news, sports, events and information in the city of Glenwood and Mills County, Iowa.


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Location: Dubai, United Arab Emirates
Date: scheduled on 2010
Architect: Dr. David Fisher
Purpose: multipurpose (offices, hotel, residential apartments)
More info: Visionary architect Dr. David Fisher is the creator of the world's first building in motion – the revolutionary Dynamic Tower. It will adjust itself to the sun, wind, weather and views by rotating each floor separately.
This building will never appear exactly the same twice.
It is amazing but you will have the choice of waking up to sunrise in your bedroom and enjoying sunsets over the ocean at dinner.
In addition to being such an incredible engineering miracle it will produce energy for itself and even for other buildings because it will have wind turbines fitted between each rotating floor (picture 2). So an 80-story building will have up to 79 wind turbines, making it a true green power plant.
The Dynamic Tower in Dubai will be 1,380 feet (420 meters) tall, 80 floors, apartments will range in size from 1,330 square feet (124 square meters), to Villas of 12,900 square feet (1,200 square meters) complete with a parking space inside the apartment. It will consist of offices, a luxury hotel, residential apartments, and the top 10 floors will be for luxury villas located in a prime location in Dubai.
The Dynamic Tower in Dubai will be the first skyscraper to be entirely constructed in a factory from prefabricated parts. So instead of some 2000 workers, only 680 will be sufficient. Construction is scheduled to be completed by 2010.
(Image credits: Dynamic Architecture ™ all rights reserved to Dr. David Fisher)


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11th Armored Cavalry Regiment
Looking for more information from military/civilian
personnel assigned to or associated with the U.S. Army
in Germany from 1945 to 1989. If you have any
stories or thoughts on the subject, please contact me.
Part of
the enthusiasm that spurred the men on during the long hours of
summer training (at Fort Know, Kentucky) might have sprung from
the knowledge that the Regiment would be headed for Germany in March
of 1957.
On 19 May 1956, official word was received from the Department of
the Army stating that the 11th Armored Cavalry would Gyro to Getmany
to replace the 6th Armored
Cavalry Regiment.
Colonel Allen D. Hulse assumed command of the 11th Armored Cavalry
in July 1956 after having completed studies at the National War
College. It was his job to prepare the Regiment for its gyroscope
to Germany.
The 11th Cavalry completed its rugged training schedule on 9 February
1957 and was ready to move out. Shortly after the arrival of the
new year an Advance party composed of officers and enlisted men
departed for Germany. These men moved into key positions with the
6th A/C in Germany and observed procedures used by that unit and
the Seventh US Army so to make the changeover as smooth as possible.
On 3 and 4 March 1957, the Regiment moved out from Fort Knox in
two groups on the first leg of their journey. Arriving in New York
they left the Brooklyn Army Terminal on 4 and 5 March on board the
USNS's BUCKNER and GEIGER. Ten days later the Regiment
had returned to Germany for the second time in its history.
The 11th Cavalry Returns To Germany
In order to accomplish its mission more effectively
the Regiment was separated into three groups. The Regimental
Headquarters and 1st Battalion
were sent to the Bavarian town of Straubing (Mansfield Kaserne)
on the Danube. The 2nd Battalion
made its home in Landshut (Pinder Kaserne) some 35 miles Northeast
of the gay and beautiful city of Munich, while the 3rd
Battalion forming the Northern point of the "Iron Triangle"
placed its Headquarters in the imperial city of Regensburg (Fort
Skelly), the meeting place and governing center of Germany during
the Middle Ages.
Soon after arriving in Germany the Regiment added four separate units to its ranks, and eliminated its medical detachment and service company. The personnel and equipment of the latter units were distributed throughout the three battalions and the headquarters company. The 83rd Army Band was added to the Regiment in Straubing, and the 502nd Armored Medical Company in Regensburg. Later the 619th Armored Engineer Company joined the unit in Straubing, and in August the 8th Ordnance Company (DS). The addition of these units gave the Regiment the fighting capabilities of a small armored division.
In keeping with the Seventh Army policy of bringing more direct control to lower echelon units, the Regiment also gave more authority to its Battalions so to give them a freer hand in carrying out their administrative tasks more effectively.
With its arrival in Germany the 11th Cav immediately took up Border operations and patrol along the German-Czech border. The 11th Cav is a front line unit, its mission -- to protect and guard the border against any Communist aggression toward the West. Along with this the Regiment forms a vital link in communications with other units in the Seventh US Army and NATO Forces here in Europe.
Regimental Commander in 1958 was Colonel James Snee; in 1959 Colonel Walter Geenwood took over. Major James Torgerson was in command of S2 /Border Ops /S4 in 1958. In 1959 he was transfered to 3rd Bat. that was having problems. Major F. G. Gosling assumed command of S2 / Border Ops in 1959. Captain Harry Peters was 2nd in command. I was personal driver for these Officers.
More on Hq-Hq Company S2/Border Ops/S4 11th A.C: Hq-Hq Company was issued two tanks (M48-A1); two personal carriers; two L19 planes; two H13 helicopters; one DeHaviland Beaver and two H34 helicopters. These were Cav. (Air Section) planes flown by army officers and Warrant Officers. Aviation Company didn't arrive untill late Dec. 1959. Early 1959 the 11th started using H34s to deploy troops wherever they could land. This later became a separate unit stationed in U.S. then went to Nam. and designated 1st Air Cav.
The 11th patrolled the German-Czech border from Whitehaus (sp?) in the north to Passau to the south. A group of engineers was stationed in Passau to destroy the bridge (if the red flag went up) entering Austria. I have no photos of the border as no one except authorized by S2/Border Officer were allowed to have a camera (while on patrol). However I am sure some patrols took the chance.
In early summer of 1958 a small plane went down near a swiming pool on the edge of Straubing. Two young men were pulled out safely. One was an 18 yr old Czech. practicing to be a civilian pilot. He stole the two seated trainer from a town in Czechoslovakia, flew to another town, picked up his friend, flew at tree top level to escape radar. He used the Danube River as a guide. He knew that when they crossed the river they would be in West Germany. The plane was moved to Mansfield Kaserne. A couple of months later it was loaded on a dragon wagon (low boy) and we took it to Munich airport - one jeep escort in front and me in the rear.
More on Border Ops: A three-lettered US federal agency had a house in Cham, a city north of Straubing. When I drove the officers to the border, we would try to stop there at some point to see what was new. They had their info downstairs in a special room. In S2 Intelligence you had to have a security clearance, "confidential" being lowest. I had a "secret" clearance. It depended on what you had access to as how high the clearance.
I had two MOS': 133.60, Intel. Spec., and 133.10, driver. I was in a special position. Per the Majors orders I was the only person allowed to take a military vehical off base without a NCO passenger. This was so I could go to a certain place or border camp or outpost without any one knowing where the Major or Captain were going. Most of the time we checked into the radio net using the S.O.P. call sign of the month. If we went at nite or later and didn't want anyone to know, we would check in at commo. room and use a different call sign. Only commo person would know .
Back to the three-lettered agency: every once in a while they would fly in. The plane was a DC3 twin engine equipped with all kinds of surveillance gear which they used flying along border. Having security clearance they let me aboard to take a look. In 1958 that kind of equipment was awesome.
M Troop was the first building by the main gate.
I did look at the pic of Ft Skelly taken in 2005. The surrounding land has changed!!! In front of the main gate used to be open fields (often pasture for sheep).
Looking down on the picture, the first building was HHQ, across the street was the troop barracks. M troop first, then the 502nd Med, then L, etc. The final barracks was the Engineer barracks.
Across the parade field was the motor pool. It appears the Germans reconfigued the back portion of the facility (we always exited the Fort at the back portion (past the ammo dump).
I have a lot of fond memories of Regensburg and my time as a Cav trooper. Thank you very much for sharing these memories with me. I am attaching a picture of me outside the main gate in early 1963.
The American flag and the Tricolor fly side-by-side in front of the camp headquarters building. The flags are raised and lowered daily in colors ceremonies.
When it comes to equipment, the French and Americans maintain their own weapons. French equipment includes a 76-MM self-propelled gun which operates with two drivers and moves forward or backward with the mere flick of a lever.
This gun knows no forward or reverse. It's all the same, the gun turns 360 degrees, a French sergeant explained.
Freedom ends at the East/West German border. Mile upon mile of fence centered in a wide, sterile strip of earth, and hundreds of slotted, ominous guard towers bring this fact home to the soldiers of the 11th ACR daily.
As guardians of this frontier, the Blackhorse Regiment is the first line of defense for the Fulda Gap, the traditional avenue of approach for many westward-bound armies throughout European history. Every moment of every day, Blackhorse soldiers are manning observation posts (OPs), providing security, and collecting vital information along the 368 kilometers of 11th ACR border responsibility.
When troopers, especially newly-arrived personnel, arrive at the border, there is an inescapable feeling that they have entered a different world. There is a dismal, oppressed air in the border region that is as much real as imagined. It is true that the weather is usually worse than at home-station cities because of the higher elevation and different terrain along most of the border area.
The initial oppression one feels is quickly replaced by an exhilarating sense of mission. One never hears the protesting question: "What are we really doing here?" There is no doubt when a soldier is staring an armed East German soldier in the face, or watching a fully-loaded Russian attack helicopter passing him. The feel of the "Iron Curtain" has instilled spirit and an urgent sense of mission leading to true career dedication in more than one young soldier.
Although the overall border mission is the same for all squadrons, each has its own facilities and methods.of accomplishing the border mission.
9. Motor pool (281 KB)
I was a member of that unit, and recall having tickets to Regensburg, and orders to Straubing in October of 1960. The travel orders were wrong, the First, Second and Third Platoons were in Regensburg at that time, along with the CO, Major Corsen. The Fourth Platoon was assigned to Straubing, and I was eventually sent to that unit.
We did bridge building exercises on the Danube River, and I was part of a detail that painted Fort Skelly God Awful Green. I took a slow motion fall from the top of the Theater Gables on that job when the extension ladder overbalanced.
I would really like to replace the unique Company Insignia brass. If I recall it correctly it was an engineer castle. I was only assigned to that unit for a total of 10 months.
I won a competitive appointment to the Military Academy Prep School and left in August of 1961 during the alert that closed the border, and saw the Berlin Wall Built. At the time of the Alert I was on a detail to Passau building a Chapel on the Border Post there. I am also curious if the Chapel was ever finished.
There are a lot of memories connected to that posting. The AFN program Hillbilly Reveille left indelible recollections of the GOOOD MORNING VIETNAM variety.
In any event, it was a pleasure finding that unit on a website.