Explore the vast range of titles available.

\"In a desperate bid to escape the bounty on his head, assassin Girton Club-Foot has returned to Maniyadoc, but the kingdom he knew no longer exists. Three kings battle for supremacy in a land ravaged by war-and one of them is his old friend Rufra. With threats inside and outside the war encampment, Girton races to find the traitor behind an assassination plot. But his magic can no longer be contained and Girton may not be able to save even himself.\"--Page 4 of cover.

Mammalian placentation is a highly regulated process and is dependent on the proper development of specific trophoblast cell lineages. The two major types of trophoblast, villous and extravillous, show mitotic arrest during differentiation. In mice, the transcription factor, glial cell missing-1 (Gcm1), blocks mitosis and is required for syncytiotrophoblast formation and morphogenesis of the labyrinth, the murine equivalent of the villous placenta. The human homolog GCM1 has an analogous expression pattern, but its function is presently unknown. We studied GCM1 function in the human-derived BeWo choriocarcinoma cell line and in first trimester human placental villous and extravillous explants. The GCM1 expression was either inhibited by siRNA and antisense oligonucleotides methods or upregulated by forskolin treatment. Inhibition of GCM1 resulted in an increased rate of proliferation, but prevented de novo syncytiotrophoblast formation in syncytially denuded floating villous explants. GCM1 inhibition prevented extravillous differentiation along the invasive pathway in extravillous explants on matrigel. By contrast, forskolin-induced expression of GCM1 reduced the rate of proliferation and increased the rate of syncytialization in the floating villous explant model. Our studies show that GCM1 has a distinct role in the maintenance, development and turnover of the human trophoblast. Alterations in GCM1 expression or regulation may explain several aspects of two divergent severe placental insufficiency syndromes, namely preeclampsia and intrauterine growth restriction, which cause extreme preterm birth.

Many years of peace have passed in Maniyadoc, years of relative calm for the assassin Girton Club-Foot. Even the Forgetting Plague, which ravaged the rest of the kingdoms, seemed to pass them by. But now Rufra ap Vthyr eyes the vacant High-King's throne and will take his court to the capital, a rat's nest of intrigue and murder, where every enemy he has ever made will gather and the endgame of twenty years of politics and murder will be played out in his bid to become the King of all Kings. Friends become enemies, enemies become friends, and the god of death, Xus the Unseen, stands closer than ever - casting his shadow over everything most dear to Girton. -- from Amazon

Objective: To establish gestational age-specific reference values of normal fetal atrioventricular (AV) time interval by spectral tissue Doppler imaging (TDI) and pulse-wave Doppler (PD) methods, and to assess their correlation with signal-averaged fetal PR intervals (ECG). Design: Cohort study. Setting: Tertiary centre for fetal cardiology. Patients and measures: 131 pregnant women between 14 and 42 weeks’ gestation underwent 196 fetal echocardiograms and 158 fetal ECG studies. TDI-derived AV intervals were measured as the intervals from atrial contraction (Aa) to isovolumic contraction (IV) and from Aa to ventricular systole (Sa) at the right ventricular free wall. PD-derived AV intervals were measured from simultaneous left ventricular inflow/outflow (in/out) and superior vena cava/aorta (V/AO) recordings. Results: Measurements were possible by ECG in 61%, by TDI in 100%, by in/out in 100% and by V/AO in 97% of examinations. Aa-IV correlated significantly better with PR intervals (y  =  0.67x + 38.29, R2 =  0.15, p < 0.0001, mean bias 8.0 ms) than did in/out (R2  =  0.10, p  =  0.002, bias 18.7 ms) and V/AO (R2  =  0.06, p  =  0.02, bias 12.4 ms). Gestational age and AV intervals were positively correlated with all imaging modalities (R2  =  0.19–0.31, p < 0.0001). Conclusion: This study showed the feasibility of fetal AV interval measurements by TDI, and established gestational age-specific reference data. TDI-derived Aa-IV intervals track ECG PR intervals more closely than PD-derived AV intervals and thus should be used as the ultrasound method of choice in assessing fetal AV conduction.

Breast cancer resistance protein, BCRP, is a multidrug resistance protein that is highly expressed in the human placenta. In cancer tissues, this protein actively extrudes a wide variety of chemically and structurally unrelated chemotherapeutic drugs and other compounds. Studies in mice have shown that in the absence of BCRP activity in the placenta, there is a 2-fold increase in the uptake in BCRP substrates into fetus. This suggests that in the placenta, BCRP extrudes compounds that would otherwise cross the syncytiotrophoblast cells into fetal circulation. The purpose of this study was to examine the expression and localization of BCRP in the human placenta throughout gestation. Tissues from 6-13, 16-19, 24-29, 32-35, and 38-41 weeks of gestation were used. Real time RT-PCR analysis demonstrated that the mRNA levels of BCRP in the placenta do not change significantly as gestation progressed. However, Western blot analysis revealed that the protein levels increased towards the end of gestation. We demonstrated that BCRP is localized to the syncytiotrophoblast of the placenta and in some fetal blood vessels within the placenta. Tissues from the early stages of pregnancy (6-13 weeks) showed fewer BCRP positive blood vessels than term tissues (38-41 weeks).

AbstractObjectiveTo determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35.DesignRandomised, phase III, double blinded international, multicentre clinical trial.Setting70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK).Participants2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses.InterventionEligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation.Main outcome measureThe primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks’ gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets).ResultsPre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes.ConclusionSupplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition.Trial registrationCurrent Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4–24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8–26·3%]; risk difference −1·8% [95% CI −10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI −6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3–18·4; p=0·01). Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.

Large placental size and low birthweight have been implicated as factors predicting high blood pressure in adulthood. Maternal anaemia has been suggested as a link. We investigated the interaction between maternal iron status and other factors known to influence birthweight and placental size. In a prospective study of 1650 low-risk, singleton, caucasian pregnancies, we related placental size and birthweight to maternal iron status, socioeconomic status, and parity. Placental morphology was assessed in 17 randomly chosen primigravid pregnancies. Parity was an important determinant of birthweight (mean standard deviation score −0·13 [SD 0·90] para 0; −0·24 [0·90] para 1; 0·32 [1·1] para 2; 0·21 [1·1] para ≥3; p < 0·0001) and placental weight (mean 655 g [SD 130]; 679 g [122]; 675 g [139]; 694 g [157], respectively; p=0·01). Cigarette smoking influenced birthweight only. Socioeconomic status had little effect after correction for parity. In addition to parity, the factors influencing placental weight were maternal height, weight, and serum ferritin concentration at booking, but not haemoglobin concentration. Serum ferritin concentrations were associated with folate intake and parity. In the placental morphology subset, serum ferritin concentration was inversely related to overall measures of peripheral villous capillarisation. Haemoglobin concentration showed no such association. These findings show a relation between maternal anaemia and placental size and birthweight across the normal range for these measures. Low ferritin concentrations in early pregnancy were associated with increased placental vascularisation at term. The association between ferritin concentration and folate supplementation emphasises the importance of preconceptional health, particularly in women at high risk of iron deficiency.

Use of fetal heart rate monitoring (FHRM) on the labour ward is common but obstetricians are less familiar with its use in theatre for non-obstetric surgery. In comparison, obstetric anaesthesia literature largely supports monitoring as an adjunct to maternal observations. The aim of this study was to systematically review the evidence on intra-operative FHRM during non-obstetric surgery. Literature was searched between 1966 and 2013 for all reports of FHRM in non-obstetric surgery; multiple sources were searched. All studies were considered; those meeting criteria underwent data extraction and quality appraisal. Forty-three cases were identified within the literature, the majority either undergoing maternal general (n = 23) or cardiovascular (n = 17) surgery. Cases were identified either from case reports or case series. Several reports discussed changes with fetal heart rate patterns on induction of anaesthesia, including reduced variability. Nearly all cases of FHRM in cardiovascular surgery reported profound fetal bradycardias on initiation of maternal by pass, which often persisted for the duration of surgery. There were three reports of delivery of the fetus as a result of the FHRM; one of these cases was reported as an inappropriate response to reduced variability. Despite the relatively high numbers of women undergoing non-obstetric surgery during pregnancy, only small numbers are reported in the literature, which may be as a result of literature bias. Practitioners considering FHRM during non-obstetric surgery need to be aware of the reported changes in FHRM with onset of general anaesthesia and maternal cardiopulmonary bypass. Individualisation of the decision to use FHRM is appropriate.

Introduction The aim of this study was to identify operator characteristics that may influence the rate of CS in the second stage compared to overall rate of CS. Methods Within this tertiary level unit in Canada, the labour ward is staffed full time by two trained obstetric staff, supported by trainees; the ultimate decisions regarding mode of delivery is made between staff and patient. Caesarean sections performed in the second stage of labour were identified from medical records and classified by the staff making the decision to perform the operation. Results Between January 2007 and December 2012, 29,779 infants were delivered in Mount Sinai Hospital. Of these, 11,140 infants were delivered by caesarean section, of which 821 were CS in the second stage of labour (7.3% of all CS, 2.7% of all deliveries overall). Male obstetricians had a lower rate of CS in the second stage compared to female obstetricians (male 7.2% vs. female 9% p = 0.01). Staff practicing less than ten years since graduation had a higher rate of CS in the second stage than those with greater than ten years post graduation experience (11% (<10 years) vs. 7% (>10 years) p < 0.01). Conclusion While fetal and maternal factors can influence the decision on mode of delivery in the second stage of labour, the personal characteristics of the operator may also have an effect. Operators may benefit from this knowledge in awareness of how this may affect their counselling of women.