logging in or signing up womenmain Saverio Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 418 Category: Entertainment License: All Rights Reserved Like it (0) Dislike it (0) Added: February 18, 2008 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: arlynna (33 month(s) ago) very nice presentation. can u sent me copy 2 my email? arlynna_79@hotmail.com tq very much Saving..... Post Reply Close Saving..... Edit Comment Close By: nituldeka (40 month(s) ago) Very nice presentation.I want a copy to teach my students.Can I?nituldeka@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: shivarekha (42 month(s) ago) very much informative. i am in a govt setup .kindly send me a cop to train my students & nurses.rekgowshi@ahoo.com Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Slide1: Overview Stephen Kennedy Theme LeaderSlide2: Endometriosis Antenatal FHR monitoring Mitochondrial genetics Pre-eclampsia NDOGTheme Leader: Stephen Kennedy: Theme Leader: Stephen Kennedy 1. Automated system for intra-partum electronic FHR analysis Leader: Chris Redman (Lionel Tarassenko, Stephen Payne) 2. Biomarkers for pre-eclampsia Leader: Ian Sargent (Pete Dobson, Paul Harrison) 3. Ultrasound screening for pre-eclampsia and IUGR Leader: Lawrence Impey (Alison Noble) 4. Pre-implantation genetic diagnosis for mtDNA diseases Leader: Joanna Poulton (Genetics Theme) 5. Pre-operative MRI for bowel endometriosis Leader: Enda McVeigh (Mike Brady)Choice of programmes: Choice of programmes Relevance to needs of NHS patients ORH Strategic Review Cross-cutting themes Industrial partnerships Achievable objectives Outstanding scientific track records Manageable within current space limitations (120m2) Slide5: Electronic fetal heart rate monitoring Chris Redman Professor of Obstetric Medicine Lionel Tarassenko Professor of Electrical EngineeringAntenatal fetal heart rate (FHR) analysis: Antenatal fetal heart rate (FHR) analysis Electronic FHR patterns are subjectively assessed to determine clinical interventions BUT, if you cannot measure them, interpretation is not science Fetal heart rate (FHR) monitoring in labour: Used worldwide for most women in labour Paper record of FHR and uterine contractions FHR from external Doppler ultrasound or scalp clip Contractions from transducer on mother’s abdomen Fetal heart rate (FHR) monitoring in labourSlide8: Features of the CTG in labourSlide9: It is relatively easy to note unusual FHR patterns when the perinatal outcome is bad It is impossible at present to count how many times this happens with totally normal outcomes The problemSlide10: All deliveries 47,752 Births with acidaemia 1,498 (3.1%) Births with low Apgar score 836 (1.7%) Births with asphyxia 254 (0.52%) Intrapartum fetal death 12 (0.025%) Magnitude of problem in Women’s Centre 1997-2005Slide11: Subjective interpretation of labour FHR recordings causes poor inter- and intra-observer reproducibility Legal implications for the ORHT Cost of claims settled April 2004-March 2007 £11,046,318 Outstanding claims April 2007: Liability already admitted > £23,000,000 Total reserved for all claims £41,895,000 Slide12: > 280,000 hours of recording time ~ 168km of paper > 110,000 records from ~ 60,000 pregnancies Computerised numerical analysis can deal with this volume of data Central computerised recording of all traces linked to clinical outcome (OXMAT) – the unique Oxford archive Computerised fetal heart rate analysis The Oxford archive (1993-2006)Automated FHR analysis Pilot work in collaboration with Engineering Science: Automated FHR analysis Pilot work in collaboration with Engineering Science Identify the features of the FHR trace which have the highest information contentAutomated FHR analysis (pilot work): Automated FHR analysis (pilot work) Map the distribution of these features in a 2-D visualisation space for reassuring (normal), non-reassuring (suspicious) and abnormal Stage I FHR tracesSlide15: Identify the region of “normality” in the visualisation map and plot the progress of labour on this mapSlide16: Plot the novelty of the FHR trace (with respect to the model of normality) and identify high novelty in real time during labourYear 1 Objectives: Extend analysis from 48 cases in pilot study to 1,000 records with stage of labour and outcome information Investigate methods for incorporating contextual knowledge and test on cases which overlap in visualisation space but have different outcomes Combine novelty score and nearest-neighbour analysis to estimate risk associated with FHR pattern Determine minimum length and quality of record to estimate risk with high confidence Year 1 ObjectivesLonger-term Objectives: Develop real-time prototype with Huntleigh Diagnostics Test prototype on new data Multi-centre RCT of automated system’s clinical value FDA/CE approval Market new product Longer-term ObjectivesSlide19: Biomarkers for pre-eclampsia Ian Sargent Professor of Reproductive Sciences Pete Dobson Academic Director, Begbroke Science Park The Problem of Pre-eclampsia: 3-5% of all pregnant women Prominent cause of maternal and perinatal death Induced delivery 7,000 -12,000 premature babies pa (UK) Complications of prematurity, including cerebral palsy Mothers and babies - both have increased risk of later cardiovascular disease The Problem of Pre-eclampsia No other complication of pregnancy is so common and so dangerous for both mother and babyAdditional Costs for the NHS: Additional Costs for the NHS Antenatal care and hospitalization Neonatal intensive and special care Long term handicap Litigation Burden of health care in later generations Slide22: Symptomless for most of its course Occurs at any time after mid-pregnancy Not predictable Relentlessly progressive Detection: repeated screening for new hypertension and proteinuria Key clinical features of pre-eclampsia Slide23: THE PROBLEMProgramme aim: To develop biomarkers: Programme aim: To develop biomarkers Serum or urine markers that appear before onset of disease Reliable predictors to rationalise allocation of antenatal careSlide25: Pre-eclampsia – a two stage disease Stage 2 (late pregnancy) Maternal syndrome systemic inflammation & endothelial dysfunction hypertension proteinuria multi-system failure Fetal syndrome poor growth Stage 1 (early pregnancy) PlacentaSlide26: Placental ischaemia/oxidative stress Placental anti-angiogenic and pro-inflammatory factors released into maternal circulation Maternal Symptoms The Causes of Pre-eclampsia Poor blood supply to the placenta Stage 1 Stage 2 Biomarkers?Candidate Placental Molecules for Biomarkers: Candidate Placental Molecules for Biomarkers sFlt-1 Endoglin PLGF VEGF Micro- and nano-particles Adverse actions on endothelium and circulationSlide28: VEGF PLGF Pro-angiogenic factors Anti-angiogenic factors Slide29: Weeks before preterm preeclampsia Changes in serum endoglin before onset of pre-eclampsia Levine et al 2006 6 weeks instead of 2 weeks warningIndustrial Collaborations: Industrial Collaborations Beckman Coulter (USA) (protocols submitted) Plasma sFlt1, VEGF, PLGF, Endoglin “Access” Immunoassay analyzer Unipath (UK) (provisionally approved) Urine sFlt1, VEGF, PLGF “Dipstick” urine test Placental Microparticles and Exosomes: Placental Microparticles and Exosomes Microparticles Small membrane vesicles (<1m) Proinflammatory and anti-angiogenic Exosomes (Nanoparticles) Microvesicles (<0.1m) Down regulate inflammatory responses Slide33: Release of placental particles into the mother’s bloodSlide34: Release of placental particles into the mother’s blood Better Prediction Improved DiagnosisFuture Developments and Collaborations: Future Developments and Collaborations Techniques developed will be applicable to other O2BRC themes (Blood, Cancer, Diabetes, Heart) Collaborations with Paul Harrison (Blood) and Adrian Harris (Cancer) Nanosight development with manufacturers (Wellcome) Isolation of microparticles and exosomes for functional studies (SEEDA grant: Pete Dobson & Phil Ligrani (Engineering) and Karl Morton (NDOG))Year 1 Objectives: Year 1 Objectives Establish new biobank and database (n = 500) Sample collection for Beckman Coulter (n = 400) and Unipath (n = 400) Establish plasma microparticle and nanoparticle baselines and normal third trimester ranges using FACS and “Nanosight” Increase FACS sensitivity for microparticle detection (Becton Dickinson)Slide37: Ultrasound screening Lawrence Impey Consultant in Fetal Medicine Alison Noble Professor of Engineering SciencePre-implantation genetic diagnosis (PGD): Pre-implantation genetic diagnosis (PGD) Dagan Wells recruited from Yale (O2BRC Senior Fellow in Reproductive Genetics funded in Year 1 by Oxford Fertility Unit) NSCAG for mtDNA diseases (2007) Collaborations: Oxford Gene Technology & Genetic Theme Year 1 No staff or support costs Embryo micromanipulator Pre-operative MRI for bowel endometriosis: Pre-operative MRI for bowel endometriosis DPhil student (Engineering Science funded) Academic Clinical Fellow (UKCRC funded) Collaborations: GE Healthcare & Imaging Theme No staff salaries, equipment or support costs in Year 1 Women’s Centre = Tertiary referral centre Identified as priority in ORHT Strategic Review Will generate additional revenue for ORHT (high tariff HRGs) Endometriosis: Strategic alliance with Pfizer: Endometriosis: Strategic alliance with Pfizer Currently funded projects fMRI pain studies Biomarker discovery Proposed collaborations Novel murine model (K-ras/luciferase) 500k SNP genome wide association in 1,200 cases + 1,400 controls SUMMARY: Clinical Training – IAT Pathway: SUMMARY: Clinical Training – IAT Pathway Academic Clinical Fellows x2 Sub-Specialty Trainee in Feto-Maternal Medicine Sub-Specialty Trainees in Reproductive Medicine x2 Clinical Lecturers x2 O2BRC Clinical Research Fellows x2 O2BRC Sub-Specialty Trainee in Feto-Maternal Medicine O2BRC Clinical Lecturer in Obstetric Medicine You do not have the permission to view this presentation. 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womenmain Saverio Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 418 Category: Entertainment License: All Rights Reserved Like it (0) Dislike it (0) Added: February 18, 2008 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: arlynna (33 month(s) ago) very nice presentation. can u sent me copy 2 my email? arlynna_79@hotmail.com tq very much Saving..... Post Reply Close Saving..... Edit Comment Close By: nituldeka (40 month(s) ago) Very nice presentation.I want a copy to teach my students.Can I?nituldeka@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: shivarekha (42 month(s) ago) very much informative. i am in a govt setup .kindly send me a cop to train my students & nurses.rekgowshi@ahoo.com Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Slide1: Overview Stephen Kennedy Theme LeaderSlide2: Endometriosis Antenatal FHR monitoring Mitochondrial genetics Pre-eclampsia NDOGTheme Leader: Stephen Kennedy: Theme Leader: Stephen Kennedy 1. Automated system for intra-partum electronic FHR analysis Leader: Chris Redman (Lionel Tarassenko, Stephen Payne) 2. Biomarkers for pre-eclampsia Leader: Ian Sargent (Pete Dobson, Paul Harrison) 3. Ultrasound screening for pre-eclampsia and IUGR Leader: Lawrence Impey (Alison Noble) 4. Pre-implantation genetic diagnosis for mtDNA diseases Leader: Joanna Poulton (Genetics Theme) 5. Pre-operative MRI for bowel endometriosis Leader: Enda McVeigh (Mike Brady)Choice of programmes: Choice of programmes Relevance to needs of NHS patients ORH Strategic Review Cross-cutting themes Industrial partnerships Achievable objectives Outstanding scientific track records Manageable within current space limitations (120m2) Slide5: Electronic fetal heart rate monitoring Chris Redman Professor of Obstetric Medicine Lionel Tarassenko Professor of Electrical EngineeringAntenatal fetal heart rate (FHR) analysis: Antenatal fetal heart rate (FHR) analysis Electronic FHR patterns are subjectively assessed to determine clinical interventions BUT, if you cannot measure them, interpretation is not science Fetal heart rate (FHR) monitoring in labour: Used worldwide for most women in labour Paper record of FHR and uterine contractions FHR from external Doppler ultrasound or scalp clip Contractions from transducer on mother’s abdomen Fetal heart rate (FHR) monitoring in labourSlide8: Features of the CTG in labourSlide9: It is relatively easy to note unusual FHR patterns when the perinatal outcome is bad It is impossible at present to count how many times this happens with totally normal outcomes The problemSlide10: All deliveries 47,752 Births with acidaemia 1,498 (3.1%) Births with low Apgar score 836 (1.7%) Births with asphyxia 254 (0.52%) Intrapartum fetal death 12 (0.025%) Magnitude of problem in Women’s Centre 1997-2005Slide11: Subjective interpretation of labour FHR recordings causes poor inter- and intra-observer reproducibility Legal implications for the ORHT Cost of claims settled April 2004-March 2007 £11,046,318 Outstanding claims April 2007: Liability already admitted > £23,000,000 Total reserved for all claims £41,895,000 Slide12: > 280,000 hours of recording time ~ 168km of paper > 110,000 records from ~ 60,000 pregnancies Computerised numerical analysis can deal with this volume of data Central computerised recording of all traces linked to clinical outcome (OXMAT) – the unique Oxford archive Computerised fetal heart rate analysis The Oxford archive (1993-2006)Automated FHR analysis Pilot work in collaboration with Engineering Science: Automated FHR analysis Pilot work in collaboration with Engineering Science Identify the features of the FHR trace which have the highest information contentAutomated FHR analysis (pilot work): Automated FHR analysis (pilot work) Map the distribution of these features in a 2-D visualisation space for reassuring (normal), non-reassuring (suspicious) and abnormal Stage I FHR tracesSlide15: Identify the region of “normality” in the visualisation map and plot the progress of labour on this mapSlide16: Plot the novelty of the FHR trace (with respect to the model of normality) and identify high novelty in real time during labourYear 1 Objectives: Extend analysis from 48 cases in pilot study to 1,000 records with stage of labour and outcome information Investigate methods for incorporating contextual knowledge and test on cases which overlap in visualisation space but have different outcomes Combine novelty score and nearest-neighbour analysis to estimate risk associated with FHR pattern Determine minimum length and quality of record to estimate risk with high confidence Year 1 ObjectivesLonger-term Objectives: Develop real-time prototype with Huntleigh Diagnostics Test prototype on new data Multi-centre RCT of automated system’s clinical value FDA/CE approval Market new product Longer-term ObjectivesSlide19: Biomarkers for pre-eclampsia Ian Sargent Professor of Reproductive Sciences Pete Dobson Academic Director, Begbroke Science Park The Problem of Pre-eclampsia: 3-5% of all pregnant women Prominent cause of maternal and perinatal death Induced delivery 7,000 -12,000 premature babies pa (UK) Complications of prematurity, including cerebral palsy Mothers and babies - both have increased risk of later cardiovascular disease The Problem of Pre-eclampsia No other complication of pregnancy is so common and so dangerous for both mother and babyAdditional Costs for the NHS: Additional Costs for the NHS Antenatal care and hospitalization Neonatal intensive and special care Long term handicap Litigation Burden of health care in later generations Slide22: Symptomless for most of its course Occurs at any time after mid-pregnancy Not predictable Relentlessly progressive Detection: repeated screening for new hypertension and proteinuria Key clinical features of pre-eclampsia Slide23: THE PROBLEMProgramme aim: To develop biomarkers: Programme aim: To develop biomarkers Serum or urine markers that appear before onset of disease Reliable predictors to rationalise allocation of antenatal careSlide25: Pre-eclampsia – a two stage disease Stage 2 (late pregnancy) Maternal syndrome systemic inflammation & endothelial dysfunction hypertension proteinuria multi-system failure Fetal syndrome poor growth Stage 1 (early pregnancy) PlacentaSlide26: Placental ischaemia/oxidative stress Placental anti-angiogenic and pro-inflammatory factors released into maternal circulation Maternal Symptoms The Causes of Pre-eclampsia Poor blood supply to the placenta Stage 1 Stage 2 Biomarkers?Candidate Placental Molecules for Biomarkers: Candidate Placental Molecules for Biomarkers sFlt-1 Endoglin PLGF VEGF Micro- and nano-particles Adverse actions on endothelium and circulationSlide28: VEGF PLGF Pro-angiogenic factors Anti-angiogenic factors Slide29: Weeks before preterm preeclampsia Changes in serum endoglin before onset of pre-eclampsia Levine et al 2006 6 weeks instead of 2 weeks warningIndustrial Collaborations: Industrial Collaborations Beckman Coulter (USA) (protocols submitted) Plasma sFlt1, VEGF, PLGF, Endoglin “Access” Immunoassay analyzer Unipath (UK) (provisionally approved) Urine sFlt1, VEGF, PLGF “Dipstick” urine test Placental Microparticles and Exosomes: Placental Microparticles and Exosomes Microparticles Small membrane vesicles (<1m) Proinflammatory and anti-angiogenic Exosomes (Nanoparticles) Microvesicles (<0.1m) Down regulate inflammatory responses Slide33: Release of placental particles into the mother’s bloodSlide34: Release of placental particles into the mother’s blood Better Prediction Improved DiagnosisFuture Developments and Collaborations: Future Developments and Collaborations Techniques developed will be applicable to other O2BRC themes (Blood, Cancer, Diabetes, Heart) Collaborations with Paul Harrison (Blood) and Adrian Harris (Cancer) Nanosight development with manufacturers (Wellcome) Isolation of microparticles and exosomes for functional studies (SEEDA grant: Pete Dobson & Phil Ligrani (Engineering) and Karl Morton (NDOG))Year 1 Objectives: Year 1 Objectives Establish new biobank and database (n = 500) Sample collection for Beckman Coulter (n = 400) and Unipath (n = 400) Establish plasma microparticle and nanoparticle baselines and normal third trimester ranges using FACS and “Nanosight” Increase FACS sensitivity for microparticle detection (Becton Dickinson)Slide37: Ultrasound screening Lawrence Impey Consultant in Fetal Medicine Alison Noble Professor of Engineering SciencePre-implantation genetic diagnosis (PGD): Pre-implantation genetic diagnosis (PGD) Dagan Wells recruited from Yale (O2BRC Senior Fellow in Reproductive Genetics funded in Year 1 by Oxford Fertility Unit) NSCAG for mtDNA diseases (2007) Collaborations: Oxford Gene Technology & Genetic Theme Year 1 No staff or support costs Embryo micromanipulator Pre-operative MRI for bowel endometriosis: Pre-operative MRI for bowel endometriosis DPhil student (Engineering Science funded) Academic Clinical Fellow (UKCRC funded) Collaborations: GE Healthcare & Imaging Theme No staff salaries, equipment or support costs in Year 1 Women’s Centre = Tertiary referral centre Identified as priority in ORHT Strategic Review Will generate additional revenue for ORHT (high tariff HRGs) Endometriosis: Strategic alliance with Pfizer: Endometriosis: Strategic alliance with Pfizer Currently funded projects fMRI pain studies Biomarker discovery Proposed collaborations Novel murine model (K-ras/luciferase) 500k SNP genome wide association in 1,200 cases + 1,400 controls SUMMARY: Clinical Training – IAT Pathway: SUMMARY: Clinical Training – IAT Pathway Academic Clinical Fellows x2 Sub-Specialty Trainee in Feto-Maternal Medicine Sub-Specialty Trainees in Reproductive Medicine x2 Clinical Lecturers x2 O2BRC Clinical Research Fellows x2 O2BRC Sub-Specialty Trainee in Feto-Maternal Medicine O2BRC Clinical Lecturer in Obstetric Medicine