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Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age
We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and understand the underlying mechanisms.
- antiepileptic drugs
- child development
- cognitive neurology
- epilepsy
- pregnancy
Animal studies have demonstrated that foetal exposure to some antiepileptic drugs (AEDs), at doses lower than those that result in structural malformations, can produce behavioural and cognitive deficits, alter neurochemistry and reduce brain weight (Fisher and Vorhees, 1992; Gaily and Meador, 2007). Further, some AEDs can produce widespread neuronal apoptosis in the immature brain similar to alcohol (Bittigau et al., 2002, 2003; Glier et al., 2004; Manthey et al., 2005; Katz et al., 2007; Kim et al., 2007; Stefovska et al., 2008). The effect is dose dependent, occurs at therapeutically relevant blood levels, and requires only relatively brief exposure. The effect has been related to reduced expression of neurotrophins and levels of protein kinases that promote neuronal growth and survival. These observations suggest that certain AEDs might produce similar adverse effects in children exposed in utero or in the neonatal period. In fact, some AEDs have been associated with reduced cognitive abilities (e.g., IQ) in children exposed in utero (Adab et al., 2004; Gaily et al., 2004; Thomson et al., 2008, Meador et al., 2009, Brombley et al., 2010). In this report, we examine the effects of foetal AED exposure on specific cognitive functions rather than global cognitive function. Verbal and non-verbal abilities were assessed at 3 years of age in children of females with epilepsy.
Participants and methods
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational study examining possible behavioural teratogenesis of AEDs. We enrolled pregnant females with epilepsy, who were on one of four AED monotherapies (carbamazepine, lamotrigine, phenytoin or valproate) from October 1999 through to February 2004, across 25 epilepsy centres in the USA and UK. We recently reported on IQ outcomes in these children at 3 years of age (Meador et al., 2009). Here, we contrast verbal and non-verbal cognitive outcomes at the age of 3 years and examine dose-dependent effects.
Consent from participants was obtained according to the Declaration of Helsinki. Institutional review boards at each centre approved the study, and written informed consent was obtained prior to enrolment. Pregnant females with epilepsy, taking carbamazepine, lamotrigine, phenytoin or valproate monotherapy, were enrolled. These four AED monotherapies were the most frequently employed during the enrolment time period. Other AEDs were not included because of insufficient numbers. Polytherapy was not included because of its association with poorer outcomes (Kluger and Meador, 2008; Harden et al., 2009a). A non-exposed control group was not included at the direction of an NIH review panel. Mothers with IQ < 70 were excluded to avoid floor effects and because maternal IQ is the major predictor of child IQ in population studies (Sattler, 1992). Other exclusion criteria included positive syphilis or HIV serology, progressive cerebral disease, other major disease (e.g. diabetes), exposure to teratogenic agents other than AEDs, poor AED compliance, drug abuse in the prior year, or drug abuse sequelae.
Information was collected on potentially confounding variables, including maternal IQ, age, education, employment, race, seizure/epilepsy types and frequency, AED dosages, compliance, socio-economic status (Hollingshead, 1975), UK/USA site, preconception folate use, use of alcohol, tobacco or other drugs during pregnancy, unwanted pregnancy, abnormalities/complications in the present pregnancy or prior pregnancies, enrolment and birth gestational age, birth weight, breastfeeding and childhood medical diseases. Children were classified as 'breastfed' if they were breastfeeding at the time of the 3 month follow-up phone call, after delivery. Cognitive outcomes were evaluated by assessors (blinded to AED) using the Differential Ability Scales (Elliott, 1990), Preschool Language Scale (4th edition) (Zimmerman et al., 2002), Peabody Picture Vocabulary Test (fourth edition) (Dunn and Dunn, 2007) and Developmental Test of Visual-Motor Integration (fifth edition) (Beery and Beery, 2004). Testing was conducted at 36–45 months of age; standardized scores were calculated. Separate investigations with very similar designs in the USA and UK were merged after initiation. Maternal IQs were determined by different measures due to the later merger; these measures included the Test of Non-Verbal Intelligence (third edition) (Brown et al., 1996) in 267 mothers (67 UK), Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999) in 20 (all UK) and National Adult Reading Test (Nelson and Willison, 1991) in 17 (all UK). Training and monitoring of neuropsychological evaluations were conducted to assure quality and consistency. As part of the training, workshops were conducted for all neuropsychological test batteries annually. In addition, each assessor was required to identify errors and provide appropriate correction for videotaped testing sessions containing errors in administration and scoring. Assessors were also required to submit their own videotape of a practice test session with record forms to the Neuropsychology Core Director for review, feedback and approval. If assessors failed, they submitted additional video assessments for approval prior to testing children in the study.
To allow comparisons across AEDs, the dosages were standardized (Meador et al., 2009). Average AED dose during pregnancy was standardized relative to ranges observed within each AED group in the intent-to-treat population by the following calculation:
Statistical analysis
The primary analysis in this substudy included 216 children with complete verbal and non-verbal outcomes at 3 years of age. Multivariate regression models were used to examine group differences, adjusting for covariates. The a priori hypothesis was that the specific AED, dose and maternal IQ were important covariates, and so these were included as predictors in a linear model with child verbal and non-verbal indices as outcomes. Other covariates were added individually to the model and were included if found to be significant (P < 0.05), or if they did not exhibit co-linearity with existing predictors. The covariates in the final model were AED, maternal IQ, pregnancy average AED dose, maternal age, race (four categories), alcohol use during pregnancy (yes/no) and preconception folate. The effects of multiple additional covariates were also examined, which included: gestational age at enrolment, gestational age at birth, epilepsy type (localization related, generalized and generalized tonic clonic for which it was unknown if localization related or generalized), seizure types (convulsive, non-convulsive), seizure frequency during pregnancy, education, employment, socio-economic status, paternal IQ, USA/UK site, tobacco use during pregnancy, birth weight, unwanted pregnancy, breastfeeding, prior pregnancy birth defects and complications, present pregnancy complications and AED compliance.
The dependent variables were verbal and non-verbal outcomes at the age of 3 years. A verbal index score was created by averaging the expressive communication and the auditory comprehension subtests of the Preschool Language Scale (Zimmerman et al., 2002), the naming vocabulary and the verbal comprehension subtests of the Differential Abilities Scales (Elliott, 1990), and the Peabody Picture Vocabulary Test (Dunn and Dunn, 2007). A non-verbal index score was the average of the block building subtest of the Differential Ability Scales (Elliott, 1990) and the Developmental Test of Visual-Motor Integration (Beery and Beery, 2004).
Multivariate regression models were adjusted for AED group, maternal IQ, standardized AED dose, maternal age at delivery, race, alcohol use during pregnancy and preconception folate. These covariates were found to be significant predictors in the multivariate model, at the 0.05 level of significance. Secondary analyses examined the following: (i) relative relationships of AED exposures to verbal versus non-verbal abilities; (ii) correlations of the individual index scores to the standardized AED doses; (iii) sensitivity of results to baseline differences in covariates; and (iv) sensitivity of results to missing data. Analyses were performed at the NEAD Data and Statistical Centre using Statistical Analysis System (SAS 9.2).
To investigate whether baseline differences in AED groups affected the results, subgroup analyses were conducted in which subgroups were defined by propensity scores (Rosenbaum and Rubin, 1983; D'Agostino, 1998). Propensity scores are predicted probabilities of receiving a treatment given baseline covariate values. Covariates are approximately equally distributed within propensity score subgroups. Propensity scores were estimated using predicted probabilities from a logistic regression model with AED treatment group (valproate versus non-valproate) as outcome. Variables related to valproate group membership were predictors in the propensity score model along with variables significantly related to age 3 verbal and non-verbal outcomes (Brookhart et al., 2006). The predictors in the propensity score model included dose, maternal IQ, maternal and gestational age, preconception folate, USA/UK site, epilepsy type, alcohol use during pregnancy, tobacco use during pregnancy, education, socio-economic status, employment status, unwanted pregnancy and race.
To investigate sensitivity of primary results to missing data (i.e. missing age 3 verbal and non-verbal outcomes), analyses were also conducted using the intent-to-treat sample (n = 310 live births including six twin pairs). One or both index scores were missing in 94 (30%); 78 (25%) had missing non-verbal scores; and 91 (29%) had missing verbal scores. Monotone data Markov Chain Monte Carlo methods were used in secondary analyses to impute missing age 3 outcomes (Li, 1988; Schafer, 1997; Little and Rubin, 2002). Variables in the imputation model included IQ scores at 2 and 3 years of age [Bailey Scales of Infant Development (Bailey, 1993); Differential Ability Scales (Elliott, 1990)], AED, dose, maternal IQ and age, gestational age at delivery, preconception folate, socio-economic status, race, tobacco use during pregnancy, employment status, education, unwanted pregnancy and alcohol use during pregnancy. Least squares mean index scores were estimated for the AED groups adjusting for maternal IQ, AED group, maternal age, dose, alcohol use during pregnancy, race and preconception folate. Standard errors and confidence intervals (CIs) of parameter estimates incorporated imputation uncertainty.
The primary analysis included 211 mothers and 216 children (five sets of twins). Mean gestational age at enrolment was 17.5 weeks (range = 3–19), which did not differ across the different AEDs. Baseline maternal characteristics are shown in Table 1. The statistical results for the primary analysis are presented in Table 2. Higher maternal IQ was associated with higher verbal (r = 0.40; P < 0.0001) and non-verbal (r = 0.26; P < 0.0001) index scores in the child. Maternal age was associated with higher verbal (r = 0.37; P < 0.0001) and non-verbal (r = 0.17; P = 0.01) index scores; this was due to lower scores in children with the youngest mothers. Overall, scores were higher in children whose mothers took preconception folate. Mean (95% CI) for verbal index score adjusted for factors in the primary analysis model was 94 (91:98) for children exposed to preconception folate, which differed (P = 0.01) from children not exposed, who had mean of 89 (86:93). Adjusted means (95% CI) for non-verbal index were 102 (98:107) for children exposed to preconception folate versus 100 (96:104) for those who were not exposed, which did not differ statistically. Verbal index scores were higher for Caucasian than other races (P < 0.0001), but non-verbal index scores did not differ across race. Children exposed to alcohol during pregnancy (n = 18) had a mean verbal index score of 97, which did not differ from the mean (97) for those not exposed (n = 198); however, non-verbal index scores differed (P = 0.02) with means for exposed (99) and unexposed (105). Note that means by race and alcohol history category used in the follow-up analyses were unadjusted due to small sample sizes in some of the subgroups.
|Antiepileptic drug
|Mothers (n)
|Mean maternal IQs (95% CI)
|100 (96:105)
|102 (98:106)
|92 (87:98)
|95 (91:100)
|98 (96:101)
|97 (94:100)
|Mean maternal ages (95% CI)
|31 (29:32)
|31 (30:32)
|30 (28:32)
|28 (26:30)
|30 (29:31)
|29 (28:30)
|Mean dosec (95% CI) (mg/day)
|781 (676:887)
|489 (430:547)
|401 (363:438)
|1012 (819:1204)
|Standardized dosed (95% CI)
|32 (28:37)
|38 (33:43)
|49 (43:54)
|25 (20:31)
|36 (33:38)
|32 (28:37)
|Gestational age at birth (95% CI) (weeks)
|38 (38:39)
|39 (39:40)
|39 (38:39)
|39 (39:40)
|39 (39:39)
|39 (38:39)
|Preconception folate n (%)
|34 (58)
|41 (59)
|17 (44)
|28 (65)
|120 (57)
|53 (57)
|Alcohol usee during pregnancy n (%)
|6 (10)
|6 (9)
|2 (5)
|4 (9)
|18 (9)
|6 (6)
|Epilepsy typesf
|Localization related n (%)
|51 (86)
|39 (56)
|28 (72)
|8 (19)
|126 (60)
|57 (61)
|Idiopathic generalized n (%)
|5 (8)
|24 (34)
|7 (18)
|32 (74)
|68 (32)
|29 (31)
|GTCSf n (%)
|3 (5)
|7 (10)
|4 (10)
|3 (7)
|17 (8)
|7 (8)
|Non-convulsive seizures n (%)
|18 (33)
|23 (37)
|14 (37)
|12 (28)
|67 (34)
|21 (25)
|None n (%)
|46 (85)
|46 (75)
|28 (76)
|33 (79)
|153 (79)
|71 (87)
|>5 Convulsions n (%)
|3 (6)
|0 (0)
|3 (8)
|1 (2)
|7 (4)
|1 (1)
|51 (86)
|62 (89)
|23 (59)
|38 (88)
|174 (82)
|70 (75)
|3 (5)
|1 (1)
|3 (8)
|1 (2)
|8 (4)
|6 (6)
|2 (3)
|3 (4)
|12 (31)
|2 (5)
|19 (9)
|12 (13)
|3 (5)
|4 (6)
|1 (3)
|2 (5)
|10 (5)
|5 (5)
a Total across antiepileptic drugs for mothers whose children had age 3 verbal index or non-verbal index scores.
b Missing = mothers for whom their children's verbal index or non-verbal index scores are missing.
c Average dose for pregnancy.
d Refer to 'Partcipants and methods' section for description of how dosages were standardized.
e Any alcohol use during pregnancy (yes/no).
f Epilepsy types: localization-related (includes cryptogenic and symptomatic); idiopathic generalized (includes absence, juvenile myoclonic, genetic and other idiopathic generalized not otherwise classified).
g Convulsions = number (%) of mothers without convulsions or >5 during pregnancy. Seizure frequency during pregnancy not reported for n = 17 mothers.
GTCS = generalized tonic clonic seizures (unknown if generalized or secondary generalized); N/A = not applicable.
|AED group
|Maternal IQ
|Standardized dose
|Maternal age
|Preconception folate
|Race (four categories)
|Any alcohol during pregnancy
Based on age 3 completer population (n = 216).
a F-value = exact F-statistic for Wilk's Lambda.
df = degrees of freedom.
Cognitive outcomes differed across AEDs. Mean verbal and non-verbal index scores for children exposed in utero to valproate were significantly lower than all other AEDs combined (P ≤ 0.0001) and across all individual pair-wise comparisons: carbamazepine (P = 0.0009), lamotrigine (P ≤ 0.0001) and phenytoin (P = 0.0006). Adjusted age 3 mean verbal and non-verbal index scores along with 95% CIs for each AED group are listed in Table 3. Overall, verbal abilities were significantly more affected than non-verbal abilities; the mean difference between verbal and non-verbal index scores across all drugs was −5.36 (95% CI = 3.5:7.2), P < 0.0001 from a paired t-test. Verbal index scores were also significantly lower than non-verbal for each AED. Using a linear model controlling for maternal IQ, dose, age of mother, alcohol use, race and folate, the mean differences (95% CI) between non-verbal and verbal indices for each AED group were: carbamazepine: 6.6 (2.1, 11.1), P = 0.0044; lamotrigine: 9.7 (5.2, 14.2), P < 0.0001; phenytoin: 6.2 (1.1, 11.2), P = 0.0171; and valproate: 14.6 (9.3, 19.8), P < 0.0001.
|Differences of valproate with other AEDsd
|Verbal indexb
|93.0 (88.6:97.3)
|96.6 (92.3:100.9)
|95.9 (91.0:100.8)
|83.9 (78.8:89.0)
|Non-verbal indexc
|99.6 (95.0:104.2)
|106.3 (101.7:110.9)
|102.0 (96.9:107.2)
|98.5 (93.1:103.8)
a Mean age 3 index scores adjusted for maternal IQ, maternal age, dose, race, alcohol use during pregnancy and folate.
b Verbal index included: (i) naming vocabulary and verbal comprehension subtests from the Differential Ability Scales (Elliott, 1990); (ii) expressive communication and auditory comprehension subscales from the Preschool Language Scale (Zimmerman et al., 2002); and (iii) the Peabody Picture Vocabulary Test (Dunn and Dunn, 2007).
c Non-verbal index included: (i) block building subtest from the Differential Ability Scales (Elliott, 1990) and (ii) the Developmental Test of Visual-Motor Integration (Beery and Beery, 2004).
d Mean difference between non-verbal and verbal index scores across all drugs was 5.36 (95% CI = 3.5:7.2), P < 0.0001 from a paired t-test.
Partial Pearson correlations for verbal and non-verbal indices to pregnancy average standardized dose, controlling for maternal IQ, are listed in Table 4, and scatter plots are depicted in Fig. 1. Dose-dependent effects for valproate were seen for both indices. Dose-dependent effects for carbamazepine were seen for the verbal index. Partial correlations for each of the individual subtest scores are given in Table 5. Similar results were found for separate analyses using either the first or third trimester dosages. Median dosages (in mg) for the whole pregnancy average dose were: carbamazepine, 800; lamotrigine, 500; phenytoin, 400; and valproate, 1000. Means (ranges) of whole pregnancy average dosages (in mg) were: carbamazepine, 781 (33–1800); lamotrigine, 489 (50–1217); phenytoin, 401 (67–750); and valproate, 1012 (133–3583).
|Verbal index
|−0.35 (0.007)
|−0.48 (0.001)
|Non-verbal ndex
|−0.39 (0.010)
Significant findings in bold.
|Preschool Language Scale (expressive communication)
|−0.40 (0.002)
|−0.41 (0.006)
|Preschool Language Scale (auditory comprehension)
|−0.29 (0.03)
|−0.51 (0.0004)
|Differential Ability Scales (naming vocabulary)
|−0.45 (0.003)
|Differential Ability Scales (verbal comprehension)
|−0.38 (0.01)
|Peabody Picture Vocabulary
|−0.34 (0.008)
|−0.39 (0.01)
|Differential Ability Scales (block building)
|−0.47 (0.002)
|Developmental Test of Visual-Motor Integration
Significant findings in bold.
The propensity score analyses demonstrated that the results are not due to differences in baseline variables related to either the child IQ outcome or chances of belonging to the valproate group. The analysis examining sensitivity of results to missing data demonstrates that the results cannot be explained by incomplete data. In the intent-to-treat sample, including 310 of the originally enrolled children, missing outcomes were imputed, and results were similar.
The present study demonstrates reduced verbal compared with non-verbal abilities in children exposed in utero to each of four commonly employed AED monotherapies. Since the verbal and non-verbal indices are standard scores based upon normative data from healthy populations, the two index scores would be expected to be equivalent. We cannot rule out that the observation of consistently greater impairments in verbal abilities is due to genetic or other environmental factors, but there is a distinct possibility that they are due to foetal AED exposure. A prior study reported reduced language abilities in children of women with epilepsy, but did not assess individual AEDs (Thomas et al., 2007). This raises the question as to why language functions might be more susceptible. As noted earlier, some AEDs can produce widespread neuronal apoptosis in the immature brain (Bittigau et al., 2002, 2003; Glier et al., 2004; Manthey et al., 2005; Katz et al., 2007; Kim et al., 2007; Stefovska et al., 2008). However, it seems unlikely that the apoptosis occurs to a greater degree in language-related neurons. In the immature brain, alcohol can not only produce apoptosis (Ikonomidou et al., 2000), but can also impair neural physiology in the remaining neurons (Medina et al., 2003, 2005). AEDs may also impair the physiology of remaining neurons, but it seems unlikely that AED-induced physiological alterations at the neuronal level would be greater in language related neurons. We hypothesize that the foetal AED exposure alters cerebral lateralization, which has a more profound effect on the neural networks underlying language functions.
In addition, our study found that both verbal and non-verbal cognitive outcomes were reduced in children exposed in utero to valproate. The effect is dose-dependent, and the magnitude of the effect is greater for verbal than non-verbal abilities. Further, foetal exposure to carbamazepine was associated with a dose-related reduction in language abilities. Strengths of our study include its prospective design, blinded cognitive assessments using standardized measures, and detailed monitoring of multiple potential confounding factors. However, caution is advised due to study limitations that include a relatively small non-population based sample, loss of enrolled subjects to analysis, lack of randomization, lack of AED blood levels, absence of an unexposed control group during pregnancy, and the relatively young age of the children at this planned interim analysis. Because the NEAD study is not a randomized trial, it is possible that confounding factors related to baseline characteristics may have affected the child's IQ. However, analyses adjusting for baseline characteristics, including the propensity analyses, suggest that the results cannot be explained by differences in baseline characteristics.
Recently, the American Academy of Neurology published new practice parameters concerning management issues for females with epilepsy (Harden et al., 2009a, b, c). With regards to cognitive teratogenesis of AED (Harden et al., 2009a), they concluded the following:
cognition is probably not reduced in children of females with epilepsy who are not exposed to AEDs in utero (two Class II studies);
there is insufficient evidence to determine if the children of females with epilepsy on AEDs in general are at increased risk for reduced cognition (conflicting Class II studies);
carbamazepine probably does not increase poor cognitive outcomes compared with unexposed controls (two Class II studies);
valproate is probably associated with poor cognitive outcomes compared with unexposed controls (two Class II studies);
cognitive outcomes are probably reduced in children exposed to valproate during pregnancy compared with carbamazepine (two Class II studies);
cognitive outcomes are possibly reduced in children exposed to valproate during pregnancy compared with phenytoin (one Class II study);
phenytoin is possibly associated with poor cognitive outcomes compared with unexposed controls (one Class II and two Class III studies);
phenobarbital is possibly associated with poor cognitive outcomes in male offspring of females with epilepsy compared with unexposed controls (two Class III studies); and
cognitive outcomes are probably reduced in children exposed to AED polytherapy as compared with monotherapy in utero (three Class II studies).
These practice parameters were formulated prior to the publication of the recent NEAD results. The present and previously published results from the NEAD study provide Class I evidence that cognitive outcomes are reduced in children exposed in utero to valproate compared with carbamazepine, lamotrigine and phenytoin. In addition, the present study supports two prior studies demonstrating an adverse effect of valproate on verbal abilities, which is greater in magnitude compared with its effect on non-verbal abilities (Adab et al., 2004; Gaily et al., 2004). The present finding of a dose-dependent effect of carbamazepine on verbal abilities is in contrast to the two prior studies (Adab et al., 2004; Gaily et al., 2004). The difference in results might be due to the fact that the verbal IQ measures used in those studies included some subtests without strong verbal factor loadings. For example, the verbal IQ from the third edition of the Wechsler Intelligence Scale for Children (Wechsler, 1991) used in the Adab et al. (2004) study, and the verbal IQ from the Revised Wechsler Intelligence Scale for Children (Wechsler, 1984) and the Revised Wechsler Preschool and Primary Scale of Intelligence (Wechlser, 1995) used in the Gaily et al. (2004) study include an arithmetic subtest. In addition, other contributing factors might include Type I error and differences across studies in AED dosage ranges and patient characteristics of the samples under investigation. As a result, further studies are needed to clarify this issue.
The majority of AED prescriptions in the USA are written for pain or psychiatric indications rather than epilepsy or seizures (Zito et al., 2006; Cascade et al., 2008). There are no published studies on cognitive outcomes in children of females taking AEDs for these other indications. However, one study found that congenital malformation rate was similar in these children compared with children of females taking AEDs for epilepsy (Holmes et al., 2001).
In clinical practice, females of childbearing potential who are prescribed AEDs with known risks should be informed of these risks. However, the observed risks of some AEDs to the child have to be balanced against the risks of seizures to the mother and child. Further complicating care, the risks for many AEDs are still poorly defined. The most consistent and severe risks for both anatomical and behavioural teratogenesis have been found for valproate (Meador et al., 2008; Harden et al., 2009a), so it seems a poor first choice for most females of childbearing potential. However, seizures in some females with generalized epilepsy may only be controlled on valproate (Marson et al., 2007). Thus, therapeutic decisions need to be individualized. Children exposed in utero to AEDs, especially valproate, should be considered at risk for cognitive deficits. Further, they may be at risk for behavioural abnormalities (Williams et al., 2001; Bromley et al., 2008; Vinten et al., 2009). Based on these findings, a raised index of suspicion should translate into more careful follow-up and evaluation of these children with appropriate referral for interventional therapies when indicated.
In conclusion, our results combined with the findings of other studies raise particular concerns that foetal valproate exposure imposes a risk of cognitive impairment, especially for higher doses and for language functions. The implications of the observed dose-dependent relationship of carbamazepine exposure to impaired verbal abilities in the present study is less clear given that this finding is in contrast to two prior studies. Additional research is needed to confirm these findings, examine risks of other AEDs, define the risks associated with AEDs in the neonate for treatment of seizures, and to understand the underlying mechanisms of adverse AED effects on the immature brain.
National Institutes of Health (2RO1-NS038455 to K.J.M., R01NS050659 to N.B.); UK Epilepsy Research Foundation (RB219738 to G.A.B.).
Conflict of interest
K.J.M. reports receiving research support from McKnight Brain Institute, MCG Foundation, Glaxo SmithKline, EISAI Medical Research, Myriad Pharmaceuticals, Marinus Pharmaceuticals, NeuroPace, SAM Technology, UCB Pharma, Epilepsy Foundation and National Institutes of Health; and also serves on the Professional Advisory Board for the Epilepsy Foundation. G.A.B. reports serving on paid advisory boards, receiving lecture fees from Pfizer, UCB and Janssen, receiving grant support from Sanofi-Aventis and Pfizer and has served as an expert witness in litigation related to neurodevelopment effects of antiepileptic drugs. N.B. and M.J.C. report that they have no significant disclosures. J.C.-S. has served as editor for Clinical Dysmorphology and as an expert witness in litigation related to neurodevelopment effects of antiepileptic drugs. L.A.K. reports consulting fee from Cyberonics, and grant support from Marinus and Medical College of Georgia. A.K. reports receiving lecture fees from GlaxoSmithKline, Ortho McNeil and UCB, consulting fees or paid advisory boards from GlaxoSmithKline, Ortho McNeil and Pfizer and grant support from GlaxoSmithKline, Novartis and Pfizer. J.D.L. that she is a member of the Professional Board of Epilepsy Foundation of Eastern PA and the speaker's bureau for UCB, Pharma. P.B.P. has previously received grant support from UCB Pharma, Marinus Pharmaceuticals, Centers for Disease Control and National Institutes of Health. M.P. reports receiving consulting and advisory board fees from UCB, Johnson and Johnson and Epifellows Foundation; lecture fees from Pfizer and UCB; grant support from UCB, Ortho McNeil, National Institutes of Health and American Epilepsy Society. D.W.L. reports receiving consulting fees from UCB, NeuroPace and Sanofi-Aventis and grant support from Myriad Pharm, Sam Technology and Novartis. No other potential conflicts of interest are reported.
The investigators would like to thank the children and families who have given their time to participate in the NEAD Study.
Appendix I: NEAD study group
Arizona Health Sciences Centre, Tucson, Arizona: David Labiner MD, Jennifer Moon PhD, Scott Sherman MD; Baylor Medical Centre, Irving Texas: Deborah T. Combs Cantrell MD, University of Texas-Southwestern, Dallas Texas: Cheryl Silver PhD; Case Western Reserve University, Cleveland, Ohio: Monisha Goyal MD, Mike R. Schoenberg PhD; Columbia University, New York City, NY: Alison Pack MD, Christina Palmese PhD, Joyce Echo PhD; Emory University, Atlanta, Georgia: Kimford J. Meador MD, David Loring PhD, Page Pennell MD, Daniel Drane PhD, Eugene Moore BS, Megan Denham MAEd, Charles Epstein MD, Jennifer Gess PhD, Sandra Helmers MD, Thomas Henry MD; Georgetown University, Washington, DC: Gholam Motamedi MD, Erin Flax BS; Harvard-Brigham and Women's, Boston, Massachusetts: Edward Bromfield MD, Katrina Boyer PhD, Barbara Dworetzky ScB, MD; Harvard–Massachusetts General, Boston, Massachusetts: Andrew Cole MD, Lucila Halperin BA, Sara Shavel-Jessop BA; Henry Ford Hospital, Detroit, Michigan: Gregory Barkley MD, Barbara Moir MS; Medical College of Cornell University, New York City, New York: Cynthia Harden MD, Tara Tamny-Young PhD; Medical College of Georgia, Augusta, Georgia: Gregory Lee PhD, Morris Cohen EdD; Minnesota Epilepsy Group, St. Paul, Minnesota: Patricia Penovich MD, Donna Minter EdD; Ohio State University, Columbus, Ohio: Layne Moore MD, Kathryn Murdock MA; Riddle Health Care, Media, Pennsylvania: Joyce Liporace MD, Kathryn Wilcox, BS; Rush University Medical Center, Chicago, Illinois: Andres Kanner MD, Michael N. Nelson PhD; The Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Missouri: William Rosenfeld MD, Michelle Meyer MEd; St. Mary's Hospital, Manchester, England: Jill Clayton-Smith MD, George Mawer MD, Usha Kini MD; University Alabama, Birmingham, Alabama: Roy Martin PhD; University of Cincinnati, Cincinnati, Ohio: Michael Privitera MD, Jennifer Bellman PsyD, David Ficker MD; University of Kansas School of Medicine-Wichita, Wichita, Kansas: Lyle Baade PhD, Kore Liow MD; University of Liverpool, Liverpool, England: David Chadwick MD, Gus Baker PhD, Alison Booth BSc, Rebecca Bromley BSc, Sara Dutton BSc, James Kelly BSc, Jenna Mallows BSc, Lauren McEwan MSc, Laura Purdy BSC; University of Miami, Miami, Florida: Eugene Ramsay MD, Patricia Arena PhD; University of Southern California, Los Angeles, California: Laura Kalayjian MD, Christianne Heck MD, Sonia Padilla PsyD; University of Washington, Seattle, Washington: John Miller MD, Gail Rosenbaum BA, Alan Wilensky MD; University of Utah, Salt Lake City, Utah: Tawnya Constantino MD, Julien Smith PhD; Walton Centre for Neurology and Neurosurgery, Liverpool, England: Naghme Adab, MD, Gisela Veling-Warnke MD; Wake Forest University, Winston-Salem, North Carolina: Maria Sam MD, Cormac O'Donovan MD, Cecile Naylor PhD, Shelli Nobles MS, Cesar Santos MD. Executive Committee: Dartmouth Medical School, Hanover, New Hampshire: Gregory L. Holmes MD; Stanford University, Stanford, California: Maurice Druzin MD, Martha Morrell MD, Lorene Nelson PhD; Texas A & M University Health Science Center, Houston, Texas: Richard Finnell PhD; University of Oregon, Portland, Oregon: Mark Yerby MD; University of Toronto, Toronto, Ontario: Khosrow Adeli PhD, Peter Wells Pharm.D. Data and Statistical Centre: EMMES Corporation, Rockville, Maryland: Temperance Blalock AA, Nancy Browning PhD, Todd Crawford MS, Linda Hendrickson, Bernadette Jolles MA, Meghan Kelly Kunchai MPH, Hayley Loblein BS, Yinka Ogunsola BS, Steve Russell BS, Jamie Winestone BS, Mark Wolff PhD, Phyllis Zaia BS, Thad Zajdowicz MD, MPH.
↵*The members of the NEAD Study Group are provided in the Appendix I.
- Abbreviations
- antiepileptic drug
- neurodevelopmental effects of antiepileptic drugs
- © The Author (2011). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: firstname.lastname@example.com


text:
Andrea Mitchell Reports 05/24/13
Veterans demand overdue benefits
About 873,000 veterans are currently waiting for disability claims in a system bogged down by paper rather than computerized lists. IAVA Chief Policy Officer Tom Tarantino discusses. ... more Duration: {{video.duration.momentjs}}
Veterans demand overdue benefits
Clinton team begins transition planning
Lessons learned from the 2016 election
Albright: Trump lives 'in a parallel...
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Ohio Secretary of State to voters:...
NBC/Survey Monkey poll: Clinton won final...
Post-debate Trump out on trail
Rep. Castro: Trump is 'parodying Russian...
GOP reactions to final face off
Clinton gaining strength in Nevada polls
Trump keeps up 'rigged' system claims
Clinton Press Secy on debate prep
Ind. candidate gains momentum in Utah
Obama disputes Trump's rigged election claims
Trump's unending conspiracy theories
What can US do to prevent hacks?
Trump, Clinton look to final debate
Obama, aides to discuss Syria options
Rep. Speier: 'We need to take this seriously'
Retrieving data...
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Andrea Mitchell Reports
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Best of MSNBC
Lawyers offer Trump accusers free legal help
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Donald Trump says he is winning this election
Will Evan McMullin win Utah?
Kellyanne Conway: Trump can't get a fair...
New poll: Clinton up double digits over Trump
Warren to Trump: We 'nasty women' have had it
Clinton team begins transition planning
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Voters not buying Trump's rigged election...
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Trump Disagrees with Pence on Striking...
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Decision 2016
Richard Branson: Trump's a 'very...
Early voting: 6.5 million votes already cast
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Andrew Sullivan on why he's now for Clinton
Donald Trump: Media & Dems rigging polls
Lawyers offer Trump accusers free legal help
Adelson's newspaper buy pays off for Trump
Why RNC fears Trump calls for poll watching
Trump camp unraveling in final stretch
Obama to fight back on redistricting for Dems
Are Democrats missing chance to eject Rubio?
Warren breathes fire beside Clinton in NH
Early voting is underway
One-on-one with Michael Moore: Part 2
One-on-one with Michael Moore
Will voters be safe from intimidation?
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Donald Trump says he is winning this election
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Clinton up in latest round of national...
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Trump and Clinton tied in battleground Ohio
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Pence questions Russia role in e-mail hacks
Schmidt: Trump undercutting US institutions
Trump's call for poll watchers stoking ...

subset: commoncrawl


text:
Bergo Tennis is a well established surface, approved and classified by The Swedish Tennis Association. The floor has been classified medium pace and the unique construction gives correct resilience, bounce and friction.
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Lines can either be created by using expansion strips or by normal painting procedure.
The unique construction will give correct resilience, bounce and friction. The perforated pattern and underneath design allows for excellent drainage capability, which will make the court dry quickly after rain. No puddles. The floor can stay outside in both summer and winter in any climate condition.
BERGO is according to evaluations made by Chalmers Technical University of Sweden, lenient with the players back and joints.
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Pallet: 180 m2
Pre-assembled sections, 4 x 3 tiles = 12 tiles: 82 m2 / pallet
Standard colours: Green and Tennis-red


text:
After a disappointing effort in the weekend at Blackburn, Arsene Wenger must make amends in their Carling Cup fixture against Shrewsbury Town.
Arsene Wenger will most likely select a young squad against a weak side like Shrewsbury.
This game is more important for Arsenal than you think. If they are unable to win, they will be knocked out from the competition, which lessens their chance of collecting silverware this season.
Wenger has to get his side back on track and hopefully shake off their dismal start to the season.
So, let's see who Arsenal should start in their encounter against Shrewsbury Town.


text:
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realmagick.com The shrine of knowledge.
Spiritual Literature
A selection of articles related to spiritual literature.
Original articles from our library related to the Spiritual Literature. See Table of Contents for further available material (downloadable resources) on Spiritual Literature.
- Trance-formation (The Cosmic Tao of the Sexes)
- The purest outpouring of love between the sexes, is as a miniature super-nova of ecstatic union. Reciprocating pleasure becomes the engine that feeds the fires of passion. Passion becomes dynamic fuel for love. It is an engine that runs with the force of a...
Body Mysteries >> Yoga
- Manifesting World Enlightenment: Part 2
- When thoughts are replaced by silence in the mind, perception arises. It is a part of the modern condition wherein the mind of humanity is constantly overwhelmed, by a million considerations and thoughts. In acquiring silence, the mind is enabled to get out...
Mind >> World Mind
- Manifesting World Enlightenment: Part 4
- There can be no doubt that the world situation today is grave. It is becoming increasingly apparent that the institutions, governments, and traditional methods of society, have little effectiveness in solving a collective crisis of global proportions. In this...
Mind >> World Mind
- Manifesting World Enlightenment: Part 3
- One of the very best ways to raise personal or group consciousness, is to MANIFEST spiritual Intentions into the environment at large. The projection of love into one's surroundings for instance, results in love being reflected back to the sender, like...
Mind >> World Mind
- Manifesting World Enlightenment: Part 5
- All things in the universe have at their basis, one fundamental essence which governs their creation, destruction and on-going actions. That singular essence is consciousness, (also known by some as God, or the Unified Field). Everywhere in Nature does...
Mind >> World Mind
- The Perpetual Raising: Part 3
- (Part 3 of 5) The body is an instrument through which we interact with the physical plane, as souls or conscious beings. As we refine this instrument through meditation, and ideally with pure foods and sufficient exercise, the body becomes, "a spiritual...
Mind >> World Mind
Spiritual Literature is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Spiritual Literature books and related discussion.
Suggested Pdf Resources
- Students, Spiritual Literature and Sivananda - The Divine Life Society
- that you are all celebrating to honour and glorify spiritual literature. I rejoice to be in ... Dharma and spiritual books are like God's own light in this world of man.
- www.dlshq.org
- Spiritual Revolution in Literature - Theosophical Society in America
- In his esthetic manifesto, Concerning the Spiritual in Art, Wassily Kandinsky (one ... Literature, music and art are the most sensitive spheres in which this spiritual.
- www.theosophical.org
- P-84 Many Paths to Spirituality - Alcoholics Anonymous
- This is A.A. General Service Conference-approved literature.
- www.aa.org
- SPIRITUAL CAPITAL: An Introduction and Literature - Metanexus
- Sean Everton provided assistance summarizing the literature on social capital. ... an overview of the vast literature relevant to the study of spiritual capital.
- www.metanexus.net
- spiritual enlightenment - Natural Thinker
- SPIRITUAL ENLIGHTENMENTI THE DAMNEDEST THING. SPIRITUAL ... sical spiritual literature; purifying yourself; abstaining from sex and so on.
- www.naturalthinker.net
Suggested News Resources
- Spiritual group to burn obscene literature
- A spiritual group based here will make a bonfire of obscene pictures and literature this Holi all over the country. The All World Gayatri Pariwar said in a statement on Thursday that it will observe Holi festival as an anti-vulgarity day.
- Karl Ove Knausgaard describes nothing happening — wonderfully
- It is hard to explain the contents of Karl Ove Knausgaard's vast series My Struggle because not much happens. Or rather: a lot of things almost happen.
- Murder in Victorian England
- Dimolianis addresses the ways that the murders were incorporated into the spiritual and occult beliefs of the time. While he clearly does not believe these ... Flanders' knowledge of Victorian literature and culture is amazing.
- Burdens and Privileges
- Back then, I tried to get with the spirit by summoning whatever lingering combativeness I could for my old editor friend's "favorite living writer" and for the paper that published him. It should have been easy.
Suggested Web Resources
- 11 Spiritual Books That Blew My Mind. | elephant journal
- Nov 4, 2012 11 books that have been game changers on my spiritual journey.
- www.elephantjournal.com
- The 12 most influential spiritual books of the past 50 years - Matador
- Jan 28, 2015 Similarly, the following twelve books have been largely influential for spiritual seekers all over the world. While some are more timeless than ...
- matadornetwork.com
- 10 Classics Of Spiritual Literature - Yoga Journal
- Aug 28, 2007 At heart, they were books about spiritual journeys, and they made spirituality seem hip and wonderful. They also introduced me to the Buddhist ...
- www.yogajournal.com
- HarperCollins 100 Best Spiritual Books of the Century | Book awards
- Book awards: HarperCollins 100 Best Spiritual Books of the Century ... Cutting Through Spiritual Materialism by Chogyam Trungpa. The Dharma bums by Jack ...
- www.librarything.com
- 26 Books Every 'Spiritual But Not Religious' Seeker Should Read
- Aug 22, 2015 If you're on a spiritual quest, these books will open you up to wonder. ... HuffPost Religion has created a book list for these spiritual seekers.
- www.huffingtonpost.com
Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
Spiritual Literature Topics
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text:
realmagick.com The shrine of knowledge.
A selection of articles related to sitar.
Original articles from our library related to the Sitar. See Table of Contents for further available material (downloadable resources) on Sitar.
- Can You Bhoga All Night Long? An Introduction to Tantra, East and West
- When you hear the word Tantra, what images come to mind? Turbans and Sitar music? Mind-blowing sex? Most people in the Western world have heard the word Tantra, but few know anything in detail about what it means. The situation in India isn't much different....
Body Mysteries >> Yoga
Sitar is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Sitar books and related discussion.
Suggested Pdf Resources
- Ravish Sitar - Electro-Harmonix
- Congratulations on your purchase of the Electro-Harmonix Ravish Sitar, ... accurately transforms your guitar into a sitar without making alterations to your.
- www.ehx.com
- Package 'sitar' - CRAN
- Package 'sitar'. July 27, 2015. Type Package.
- cran.r-project.org
- The Electronic Sitar Controller - Princeton Sound Lab
- Electronic Sitar, ESitar, Indian String Controller, MIDI. Controller, Human ... 1.
- soundlab.cs.princeton.edu
- Sitar Making in India - HACKLEMAN SHOP
- www.hacklemanshop.com
- dinner menu (pdf) - Sitar Indian Cuisine
- Sitar uses dairy, nuts and gluten in some of the dishes. To avoid any food allergies clients are encouraged to call us at. 919-490-1326 for any questions or ...
- sitar-indiancuisine.com
Suggested News Resources
- Sitar Satire
- My name is Ravi Sankar and I don't play the sitar but I love Trinidad & Tobago music. I know Ravi Shankar and his daughter, Anoushka, are famous for playing the sitar. I will tell people my name and I will get a little tease in-between.
- Fascinated by the Sitar, He Made it His Career - Sebastian Dreyer
- KOCHI: It was an unplanned tryst with the Sitar that awaited Sebastian Dreyer from Potsdam, Germany, when in the 90s he chanced upon a recording of noted sitar player the late Nikhil Banerjee.
- Sitar Wonder Anoushka Shankar to Perform at CAP UCLA in April 2016
- Sitar master and composer Anoushka Shankar is set to perform on Wednesday, April 13 at Royce Hall at UCLA in Los Angeles, California. Anoushka will appear with supporting musicians Manu Delago, the Austrian percussionist and frequent collaborator of ...
- When sitar meets guitar, this man makes magical music
- Puducherry: Puducherry-born and bred musician Soham Munim has spent most of his boyhood years practicing classical music on the sitar. But now, the 30-year-old musician is looking at innovation armed with a brand new instrument of his invention - the ...
Suggested Web Resources
- Sitar - Wikipedia, the free encyclopedia
- The sitar English pronunciation: /ˈsɪtɑːr/ or /sɪˈtɑːr/ is a plucked stringed instrument used mainly in Hindustani music and Indian classical music.
- en.wikipedia.org
- Amazing Sitar Player - YouTube
- Apr 1, 2008 Check out The Biryani Boys every Sunday @5pm on ITV as part of "Sangeet Sabha", a half hour show dedicated to Classical Indian Music!
- www.youtube.com
- Sitar Indian Cuisine | New Haven, CT 06511HOME
- Sitar Indian Cuisine | New Haven, CT 06511 | Welcome to the Mystical World of Fine Indian Cuisine. We are located at 45 Grove Street, New Haven, CT ...
- sitarnewhaven.com
- Sitar Indian Restaurant | Order Online | Nashville, TN 37203 | Indian
- View Sitar Indian Restaurant menu, Order Indian food Pick up Online from Sitar Indian Restaurant, Best Indian in Nashville, TN.
- www.sitarindiannashville.com
- Sitar Indian Cuisine: Restaurants - Durham, NC
- Sitar Indian Cuisine is one of the most experienced restaurants in Durham, NC.
- sitar-indiancuisine.com
Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
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text:
Blues Alley Presents Jonathan Butler
* Additional fees apply. No coupon or promo codes necessary to enjoy the displayed discount price.
The last date listed for Jonathan Butler was Friday July 19, 2013 / 8:00pm.
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Featured review from Juanita NewellRed Velvet
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Loved the opening act and Jonathan Butler. Very entertaining. What I didn't like was that I had to stand on the 2nd level the entire time during the show. My other visit to the Filmore was standing on the first floor and VIP seating on the 2nd floor. For Jonathan Butler show they had seating on the first floor, some seating on the 2nd floor, but my ticket was for standing only. I could see well; and I could dance because I had to stand. It was fun!
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The performance was great - and good seats! Food and beverages were available.
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The Filmore venue was excellent. I had a top balcony standing seat...However, I was able to see the concert very well. There is nota bad seat in the house. I will be attending concerts at teh Filmore in the future. Also, the food was great as well.


text:
Harsh occupations, life expectancy and social security
Should special pension provisions be offered to workers in harsh occupations? We address this question in an optimal tax setting where individuals differ in longevity and occupation. Longevity is private information but workers in harsh occupations have on average shorter lifes than workers in safe occupations. We adopt a weighted utilitarian social objective to partially redress the implicit redistribution from short- to long-lived individuals that the unweighted utilitarian objective entails. We show that there is a case for differentiating the social security policy by occupation. We also show that short-lived workers are induced to overconsume when young and to retire early in order to prevent mimicking by long-lived ones. This is achieved by taxing, often quite heavily, the savings and the earnings from prolonging activity of short-lived individuals.
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|Date of creation:
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|Date of revision:
|Contact details of provider:
| Postal: +61 2 6125 3807
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text:
There are currently over 0.7 million Poles living in the UK, including over 500 000 who reside in London. It is a prospective market and a great advertising platform! They are young, resourceful, urban and dynamic. Polish community members are also more likely to own luxury brands. They are keen to try new services and technologies - keen to try YOUR PRODUCTS.
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77 search results for Martha Plimpton
The Goonies
Type: Video | Date: Monday, Aug 15, 2016Kids stumble upon a treasure map and undertake a harrowing mission to recover pirate treasure. Produced by Steven Spielberg!
Watch: Garret Dillahunt and Martha Plimpton talk 'Raising Hope'
Type: Post | Date: Tuesday, Oct 9, 2012Nakedness and playing a functional TV couple are discussed
Raising Hope - Interview with Garret Dillahunt and Martha Plimpton
Type: Video | Date: Tuesday, Oct 9, 2012Garret Dillahunt and Martha Plimpton sit down with Dan Fienberg share their philosophies about their character relationship and working with the babies in this interview for Fox comedy Raising Hope.
25 years ago today: 'Home Alone' opened in theaters
Type: Article | Date: Monday, Nov 16, 2015Plus: Rory's first kiss on 'Gilmore Girls,' the first 'Harry Potter' film was released, a daytime TV record, and more
Raising Hope - Lucas Neff & Martha Plimpton
Type: Video | Date: Tuesday, Sep 28, 2010The Chances discuss writing, babies and the Leachman
'Goonies 2' is happening according to director Richard Donner
Type: Article | Date: Saturday, Apr 5, 2014Are Data, Chunk, and Sloth really returning?
Raising Hope
Type: Event | Date: Friday, Apr 4, 2014The series ends tonight.
Watch: Martha Plimpton and Lucas Neff talk 'Raising Hope'
Type: Post | Date: Tuesday, Sep 28, 2010FOX comedy stars talk babies, Cloris Leachman and more
Raising Hope
Type: Event | Date: Friday, Nov 15, 2013The fourth season starts tonight.
'Game of Thrones' rules the Creative Arts Emmys
Type: Article | Date: Sunday, Sep 16, 2012Martha Plimpton, Jimmy Fallon, Neil Patrick Harris, 'Homeland' also win


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Ineco is a global leader in transport engineering and consultancy. For over 40 years, its expert team of around 2,500 employees has been contributing to the development of infrastructures in the aviation, railways, roads, urban transport and ports sectors, offering solutions in more than 40 countries. Our high-level technological knowledge brings advanced solutions to the ...
based in Madrid, SPAIN.
VALVULAS VS, S.L. is a company dedicated to the manufacture of stainless steel and special alloy valves for the chemical and petrochemical industries. Backed up by its over thirty year experience in the manufacturing of globe, gate, check, y-pattern, drain and diaphragm valves, filters, sight glasses. We supply the biggest Spanish and foreign companies of the chemical ...
based in Muskiz-Bizkaia, SPAIN.
GeoPrecision GmbH specialises on the development of original data capture systems. Additionally, new sensor concepts will be brought to the market, e.g. the patented pF-meter which is registering the matrix potential of the soil. Because we are using our own calibration facilities, we are able to offer a fast and efficient service for our customers. Due to our high level ...
Distributor in Sevilla, SPAIN.
Geotex, SA is a company dedicated to the manufacture and marketing of geosynthetics: geotextiles, geocomposites, geomembranes, related products and synthetic fibres. Located in Rio Tinto Mines, the mining town of Huelva, the company began operations in mid 2004, and today is one of the most important manufacturers nationwide
based in Huelva, SPAIN.
Atlantis is a leading provider of global environmental market solutions in the field of stormwater management, collection and purification. An international company, it has developed an ecologically sustainable solution using patented `at source` drainage, purification and detention technologies. We offer a comprehensive range of skills and expertise encompassing all ...
Office in SPAIN.
We are customer oriented and we continually seek out innovative and valuable solutions for our clients. Agronomy analyses, water analyses, environmental analyses.
based in Burguillos, SPAIN.
FERRER, It takes as a corporate purpose the analysis and the quantitative evaluation of the diverse systems of control of the underground waters, in the area of the hidrogeology applied in works of building and works of civil engineering. It includes the execution of wells, drills, monitoring and tests of pumping as well as the implantation of the pertinent systems of ...
based in Valencia, SPAIN.
Geoenvironmental engineering firm based in Madrid, Spain. Miliarium Aureum, S.L. are official distributors for the software packages Visual MODFLOW, AquaChem, Hydro GeoAnalyst y HydroGeoBuilder for Schlumberger Water Services.
Grindex is a world leader in electrical submersible pump technology for demanding applications such as construction, mining and heavy industry. The pumps are known for their high reliability, durability and dependability. Thanks to the built-in motor protection and the air valve, the pumps can run unsupervised for longer periods, and even run dry for a length of time. ...
Distributor in SPAIN.
TENÍAS, S.A., a company specialized in the manufacture of front loaders, owns the technology and experience enough for its recognition both in national and international markets. All its sections are equipped with the latest machinery and technology means that make the most of its manufacture quality. There is no better proof of the confidence the customers have in Tenías ...
based in Ejea de los Caballeros, SPAIN.
Over more than 60 years as manufacturers of scientific equipments for laboratories, J.P. Selecta has achieved in consolidating a prestigious position in this market, distributing to more than 100 countries. The production of catalogues in different languages as well as our participation in numerous exhibitions internationally recognized, such as: Analytica, Achema, ...
based in Abrera, SPAIN.
NOVAterra has a skilled profesional team with a wide experience in polluted soil and ground water evaluation, detailed investigation, and remediation plus in human and ecological risk analisys. NT is a registered firm for severa spanish regional governments.
based in BARCELONA, SPAIN.
Aleximport´s activity focuses on Importing, Distributing and After Sales Service in the Spanish market of attachments for Public Works, Demolition, Recycling, Environment, Construction and Mining.
based in San Sebastián, SPAIN.
Metricstream is the leading provider of solutions for Governance, Risk, Compliance (GRC), and Quality Management. Organizations today need a systematic approach to defining and managing GRC initiatives and quality management programs through a sustainable and integrated process that is aligned with the corporate strategy instead of a series of unrelated tactical projects. ...
Office in Madrid, SPAIN.
The Aquatec Group are creators of innovative instruments, services and solutions for measurement, monitoring and communication underwater. They provide instrumentation solutions for all water environments and service a wide range of applications, including offshore structures and pipelines; oceans, estuaries, rivers and lakes; marine mammals and fisheries; and marine ...
TDI-Power Attachments specializes in providing concrete mixers, vibratory rollers, broom buckets, cold planers and trenchers. Our concrete mixers are designed to provide homogeneous mixing of concrete and cement. They are used in construction and public works. Our concrete mixer is provided with a safety cap, electrical connector wiring and pressure control valves. Our ...
based in Barcelona, SPAIN.
Terratech, Inc. is a multinational company specializing in providing commercial and residential infrastructure solutions from modular housing to soil stabilization and road construction. The Terratech team of engineering, design and construction experts are committed to supplying customers with products and methods that provide real solutions for their infrastructure, ...
Office in Cáceres, SPAIN.
Indus Agar s.a., spanish company located in Santander, Cantabria (Spain) was born in 1960, after designing a simple and effective solution to the continual problems that metallic pumps created at that time to the extractive industry when handling abrasive and corrosive fluids. Indus Agar s.a. manufactures its own patents. Our products consist of a wide range of ...
based in Santander, SPAIN.
DG is a firm that optimizes the buildings, the resilience of cities and facilitates the protection of citizens at risk of dynamic loads and flooding (including geodynamic risks). To achieve this goal, DG reconciles cost savings with what we have called `technological protection" (prediction +preventive engineering+ early warning+ immediate action), provided under an ...
based in ALMERIA, SPAIN.
Spanish company dedicated to the soil remediation. Contaminated soil remediation services.
based in Candas, SPAIN.
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The films of Hayao Miyazaki and the other animators associated with Tokyo's Studio Ghibli are renowned for their illustrative elegance and wondrous imagination. Funny, then, that the company originated in 1985 as a thumb to the eye of the rest of the Japanese anime industry. Its name translates to "Mediterranean wind," the idea being that the studio was constructed to blow away all others. As the NW Film Center's month-long retrospective shows, it just about has.
Although it actually predates his co-founding of Ghibli by a year, Miyazaki's second feature, the 1984 post-apocalyptic folk tale Nausicaä of the Valley of the Wind (7 pm Friday, 1 pm Saturday, 4:15 pm Sunday, May 4-6), introduces the visual style and thematic principles that would become the studio's hallmarks. In a dystopian future, mankind is not only wholly separated from nature but deathly afraid of it—which is understandable, considering nature consists of giant insects whose eyes glow red with rage whenever a human disturbs their habitat. Only Nausicaä, a hang-gliding eco-warrior Christ-figure in a short blue dress and thigh-high boots, possesses the interspecies empathy to bring harmony back to a war-ravaged planet. It's a stunning environmentalist parable.
In the subsequent years, Miyazaki broke through to international audiences with modern-day fables like My Neighbor Totoro (4 pm Saturday, 7 pm Sunday, May 5-6), Princess Mononoke (7 pm Saturday and Monday, 4 pm Sunday, May 12-14), and his grandest achievement, 2001's Spirited Away (7 pm Thursday, 1:30 pm Saturday, May 24 and 26), the only foreign film to ever win the Oscar for Best Animated Feature. Meanwhile, Ghibli co-founder Isao Takahata established a reputation of his own, if primarily just in Japan, directing the coming-of-age period piece Only Yesterday (4 pm Saturday, 7 pm Sunday, May 12-13) and his own environmentalist fantasy Pom Poko (7 pm Friday, 2 pm Sunday, May 25 and 27). Strangely, his personal masterpiece, the powerful war drama Grave of the Fireflies, is conspicuously missing from the festival lineup, while his only intermittently amusing comic-strip adaptation, My Neighbors the Yamadas (4:30 pm Saturday, 7 pm Sunday, May 19-20), makes the cut. It's the closest thing to Cars 2 in the studio's otherwise spotless résumé.
SEE IT: Castles in the Sky: Miyazaki, Takahata, and the Masters of Studio Ghibli starts Friday. Check nwfilm.org for a complete schedule.


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Americas Best Bath is the Aging in Place Professionals!
Helping homeowners regain their bathing independence.
If you are ready to regain your bathing mobility, then Americas Best Bath has the bath accessibility products you're looking for! Our bath and shower products are designed with your safety in mind. Let our professionals help make your step-in tub purchase fast, easy and affordable.
Americas Best Bath is the leader in bathing accessibility products. We have bath and shower solutions that will modernize your bathing experience and give you the added safety you need for you and your loved ones. Choose from products such as walk-in tubs, low threshold showers and barrier free showers.
Walk-in tubs for safe and luxurious bath
Our walk-in tubs are an outstanding product! Regaining your bathing independence has never been easier and has never felt so luxurious. We want everyone to enjoy their bathing experience without having to worry about falling while getting in or out of the tub. The low-threshold door is low to the ground and makes stepping into the tub a breeze. The TurboDrain feature will have your bath water drained in no time! Safety features also include no-slip flooring, chair-height seat, safety grab bars and easy reach controls. Enjoy spa-like features such as Hydrotherapy, Chromatherapy and Aromatherapy for a relaxing and soothing bath every time.
If you enjoy showering but are looking to add additional safety to your showering experience, Americas Best Bath has the perfect product for you! With our low barrier and barrier-free shower bases, no more stepping into your shower. With the shower base flush with the floor, the shower becomes wheelchair accessible.
We have helped countless homeowners find bath accessibility solutions to help them regain their bathing independence. You will love bathing again once we have installed your new, durable, modern looking bath or shower solution. Our professional installers are the best in the business and they understand the importance of installing your bath solution in a timely manner. Our experienced representatives will be happy to answer any questions you may have about our products and services. Call or contact us today to schedule a free in-home consultation with one of our representatives. You owe it to yourself to find out more about our high-quality products that can help you regain your bathing independence.


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How to change Hydro Oil on Scag Pro V?
Discussion in 'Mechanic and Repair' started by dobronos, Oct 11, 2012.


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For Sale: Ritz-Carlton Back Bay Boston
Rumor has it that the Grande Dame of Boston hotels, the oldest Ritz-Carlton in the United States, is on the market. Located on fashionable Newbury Street and the Public Garden, the 273-room luxury hotel celebrated its 75th anniversary with a major renovation in 2002. As reported by the Boston Herald:
India-based newspapers and at least one TV station reported yesterday that Indian Hotels Co. Ltd., owner of Taj Hotels Resorts and Palaces, will buy the Ritz for $170 million. But New York-based Millennium Partners, which has owned the Boston hotel for seven years, said it has not reached a deal to sell it.
Apparently, since the last summer purchase of The Pierre in Manhattan, Taj Hotels has been on the prowl for similar properties in gateway US cities "to build a five-star hotel brand under The Pierre flag."
Castle Hotel and Spa
Tarrytown, United States
Situated on sprawling hilltop acres overlooking the Hudson... more >>
CopperWynd Resort and Club
Fountain Hills, United States
CopperWynd Resort and Club, a boutique Arizona resort property... more >>
Rusty Parrot Lodge And Spa
Jackson, United States
The Rusty Parrot Lodge and Spa offers the finest in Jackson Hole... more >>
Opus Hotel Vancouver
Vancouver, Canada
More than somewhere to stay, OPUS Vancouver is somewhere to be.... more >>
Wentworth Mansion
Charleston, United States
Welcome to the Wentworth Mansion. To step through the doors is... more >>


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Product Information
Built on the FriXion X-Axis rubber outsole the Wildcat digs into any surface for excellent traction and added cushion. The single density midsole provides excellent cushioning and is coupled with a plush LaSpEVA 2.4 mm lasting board. A great all around trail runner for people looking for great stability and cushion.
Product Features
- AirMesh upper with a Trail Cage frame and Transkinetic heel stabilizer for stability, as well as UreTech reinforcements in high wear areas
- FriXion X-Axis rubber outsole digs into any surface for excellent traction and added cushion
- Honeycomb mesh lining (in the tongue and heel only)
- La Sportiva's Impact Brake System proprietary technology in outsole design has the lugs of the soles oriented in opposing slanted directions, increasing braking power by an average of 20% and decreasing impact forces by an average of 20%
- Nylon-molded Flex Transfer shank gives you torsional stability and flexibility with each step
- Plush 2.4mm LaSpEVA lasting board
- Single density MEMlex midsole provides excellent cushioning
Product Specifications
- Brand
- La Sportiva
- Gender
- Male
- Color
- Turtle
- Size
- Euro 41.5
- Age
- Adult
- 801216118011
- Ship Dimension
- 8 x 15 x 6 inches
- Ship Weight
- 2.5lbs.


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It is opportunity that drives me. Because we deserve healthier, more vibrant places to live in, living out the vision to overcome obstacles and understand opportunity is a journey worth taking.
I felt overwhelmed by how much there was to see, and I didn't know how to structure my visit. I wanted to see everything, and simultaneously, I longed to take my time with the artworks. Then, as I was meandering through the Greek and Roman statuary, all of a sudden I came to a halt...
The setting was beautiful. Compared to Delhi's flat, dusty, crowded surroundings, this was steep and quiet. The roads twisted and pulled and unbalanced us as we travelled up and around the mountains. They led us to falls, mountain towns, overlooks on the valley below, and the Himalayas beyond...
Here are a few of the fabulous folks who create Culture Keeper:
Jordy Van Den Nieuwendijk / Capucine Fachot / Jill Devries / Matthew Stackowicz / Dusty St. Amand / Paul Octavious / Nicolo Gentile / Maren / Keegan Keene / Andrew Skipper / Jonathan Geels / Merry Moore / Moktar Beyrouth / Mae Stier / Bryan Dale / Michael Newsted / Enuma Okoro / Stephani Cantani / David Vosburg / Grant Legan / Marina Gross-Hoy / Gabe Nielson / Roshanda Cummings / Megan + Mike Gilger / Hannah Stone / Jane Mow / Jordan Dale Young / Zach Stone / Ricky Cohete /John Hanson / Bradley Leach / Caroline + Jayden Lee / Grant Beachy / Welelah Mar / Micah Ling / Olivia Deters / Rachel Berbec /
Creative Director - Jonathan Randall Grant
Managing Editor- Kami Rice
Social Media Director- Merry Moore


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