http://www.dspace.cam.ac.uk:80/handle/1810/223973 Wed, 22 May 2013 15:43:44 GMT 2013-05-22T15:43:44Z http://www.dspace.cam.ac.uk:80/handle/1810/240754 Title: Risk of placenta previa in second birth after first birth cesarean section: a population-based study and meta-analysis Authors: Gurol-Urganci, Ipek; Cromwell, David A; Edozien, Leroy C; Smith, Gordon CS; Onwere, Chidimma; Mahmood, Tahir A; Templeton, Allan; van der Meulen, Jan H Abstract: Abstract Background Objective: To compare the risk of placenta previa at second birth among women who had a cesarean section (CS) at first birth with women who delivered vaginally. Methods Retrospective cohort study of 399,674 women who gave birth to a singleton first and second baby between April 2000 and February 2009 in England. Multiple logistic regression was used to adjust the estimates for maternal age, ethnicity, deprivation, placenta previa at first birth, inter-birth interval and pregnancy complications. In addition, we conducted a meta-analysis of the reported results in peer-reviewed articles since 1980. Results The rate of placenta previa at second birth for women with vaginal first births was 4.4 per 1000 births, compared to 8.7 per 1000 births for women with CS at first birth. After adjustment, CS at first birth remained associated with an increased risk of placenta previa (odds ratio = 1.60; 95% CI 1.44 to 1.76). In the meta-analysis of 37 previously published studies from 21 countries, the overall pooled random effects odds ratio was 2.20 (95% CI 1.96-2.46). Our results from the current study is consistent with those of the meta-analysis as the pooled odds ratio for the six population-based cohort studies that analyzed second births only was 1.51 (95% CI 1.39-1.65). Conclusions There is an increased risk of placenta previa in the subsequent pregnancy after CS delivery at first birth, but the risk is lower than previously estimated. Given the placenta previa rate in England and the adjusted effect of previous CS, 359 deliveries by CS at first birth would result in one additional case of placenta previa in the next pregnancy. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Mon, 21 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240754 2011-11-21T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238072 Title: In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer Authors: Saidi, Samir A; Holland, Cathrine M; Charnock-Jones, D Stephen; Smith, Stephen K Abstract: Abstract Fenofibrate, an agonist of PPAR-alpha, in doses above 25 μM, inhibits proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show that these effects are potentiated by retinoic acid, an agonist of the retinoid-X-receptor. DNA content analysis shows that G1/S phase progression through the cell cycle is inhibited. Independent Component Analysis of gene microarray experiments demonstrated downregulation of Cyclin D1 (CCND1) and associated changes in cell cycle gene expression. Expression of PPAR-alpha mRNA was reduced by >75% using RNA-interference but this resulted in only minor changes in biological effects. A nude mouse model of endometrial carcinoma was used to investigate the effect of fenofibrate in vivo but failed to show consistent inhibition of tumour growth. Conclusion The combination of fenofibrate and retinoic acid is a potent inhibitor of Ishikawa endometrial cancer cell growth in vitro. Mon, 27 Mar 2006 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238072 2006-03-27T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237938 Title: Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study. Authors: Pasupathy, Dharmintra; Dacey, Alison; Cook, Emma; Charnock-Jones, D Stephen; White, Ian R; Smith, Gordon C S Abstract: Abstract Background There have been dramatic changes in the approach to screening for aneuploidy over the last 20 years. However, the approach to screening for other complications of pregnancy such as intra-uterine growth restriction, pre-eclampsia and stillbirth remains largely unchanged. Randomised controlled trials of routine application of high tech screening methods to the general population have generally failed to show improvement in outcome. We have previously reviewed this and concluded it was due, in large part, to poor performance of screening tests. Here, we report a study design where the primary aim is to generate clinically useful methods to screen women to assess their risk of adverse pregnancy outcome. Methods/design We report the design of a prospective cohort study of unselected primiparous women recruited at the time of their first ultrasound scan. Participation involves serial phlebotomy and obstetric ultrasound at the dating ultrasound scan (typically 10–14 weeks), 20 weeks, 28 weeks and 36 weeks gestation. In addition, maternal demographic details are obtained; maternal and paternal height are measured and maternal weight is serially measured during the pregnancy; maternal, paternal and offspring DNA are collected; and, samples of placenta and membranes are collected at birth. Data will be analysed as a prospective cohort study, a case-cohort study, and a nested case-control study. Discussion The study is expected to provide a resource for the identification of novel biomarkers for adverse pregnancy outcome and to evaluate the performance of biomarkers and serial ultrasonography in providing clinically useful prediction of risk. Wed, 19 Nov 2008 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237938 2008-11-19T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237913 Title: Causes of death and associated conditions (Codac) - a utilitarian approach to the classification of perinatal deaths Authors: Froen, J Frederik; Pinar, Halit; Flenady, Vicki; Bahrin, Safiah; Charles, Adrian; Chauke, Lawrence; Day, Katie; Duke, Charles W; Facchinetti, Fabio; Fretts, Ruth C; Gardener, Glenn; Gilshenan, Kristen; Gordijn, Sanne J; Gordon, Adrienne; Guyon, Grace; Harrison, Catherine; Koshy, Rachel; Pattinson, Robert C; Petersson, Karin; Russell, Laurie; Saastad, Eli; Smith, Gordon C S; Torabi, Rozbeh Abstract: Abstract A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD), although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes. We tested the Causes of Death and Associated Conditions (Codac) classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions. The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies), two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy), a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal). For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured. The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions associated with them, and the most common clinical scenarios for future study and comparisons. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 09 Jun 2009 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237913 2009-06-09T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237770 Title: MMP1 bimodal expression and differential response to inflammatory mediators is linked to promoter polymorphisms Authors: Affara, Muna; Dunmore, Benjamin J; Sanders, Deborah A; Johnson, Nicola; Print, Cristin G; Charnock-Jones, D Stephen Abstract: Abstract Background Identifying the functional importance of the millions of single nucleotide polymorphisms (SNPs) in the human genome is a difficult challenge. Therefore, a reverse strategy, which identifies functionally important SNPs by virtue of the bimodal abundance across the human population of the SNP-related mRNAs will be useful. Those mRNA transcripts that are expressed at two distinct abundances in proportion to SNP allele frequency may warrant further study. Matrix metalloproteinase 1 (MMP1) is important in both normal development and in numerous pathologies. Although much research has been conducted to investigate the expression of MMP1 in many different cell types and conditions, the regulation of its expression is still not fully understood. Results In this study, we used a novel but straightforward method based on agglomerative hierarchical clustering to identify bimodally expressed transcripts in human umbilical vein endothelial cell (HUVEC) microarray data from 15 individuals. We found that MMP1 mRNA abundance was bimodally distributed in un-treated HUVECs and showed a bimodal response to inflammatory mediator treatment. RT-PCR and MMP1 activity assays confirmed the bimodal regulation and DNA sequencing of 69 individuals identified an MMP1 gene promoter polymorphism that segregated precisely with the MMP1 bimodal expression. Chromatin immunoprecipation (ChIP) experiments indicated that the transcription factors (TFs) ETS1, ETS2 and GATA3, bind to the MMP1 promoter in the region of this polymorphism and may contribute to the bimodal expression. Conclusions We describe a simple method to identify putative bimodally expressed RNAs from transcriptome data that is effective yet easy for non-statisticans to understand and use. This method identified bimodal endothelial cell expression of MMP1, which appears to be biologically significant with implications for inflammatory disease. (271 Words) Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 19 Jan 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237770 2011-01-19T00:00:00Z