<b><i>Objective:</i></b> The study aimed to investigate the association b... more <b><i>Objective:</i></b> The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. <b><i>Methods:</i></b> We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. <b><i>Results:</i></b> The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (&lt;0.3 MoM and &lt;0.5 MoM) were independently associated with sPTB, low BW, PE, GH, and a composite adverse pregnancy outcome score, with odds ratios between 1.81 and 4.44 on multivariable logistic regression analyses. <b><i>Conclusions:</i></b> Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.
Australasian Journal of Ultrasound in Medicine, 2017
The placenta is the link between mother and fetus and its function is central to a successful pre... more The placenta is the link between mother and fetus and its function is central to a successful pregnancy. The predominant theory within the literature is that the development of placental dysfunction is a result of abnormal trophoblast invasion early in pregnancy. Knowledge of the development of the early placenta and the establishment of the fetomaternal circulation assists in understanding the origins of placental dysfunction which manifest later in pregnancy.Perinatally, chronic placental dysfunction may result in a growth‐restricted fetus, maternal problems such as gestational hypertension, pre‐eclampsia, eclampsia and pregnancy complications such as placental abruption, preterm labour and delivery. In addition, the growth‐restricted fetus and the mother are at an increased risk of a myriad of disorders later in life.The role of ultrasound in the assessment of first trimester pregnancy is evolving with the potential for value in the prediction of placental function in later pregn...
Introduction: Standardization of first-trimester nuchal translucency (NT) image acquisition is cr... more Introduction: Standardization of first-trimester nuchal translucency (NT) image acquisition is crucial to the success of screening for Down syndrome. Rigorous audit of operator performance and constructive feedback from assessors maintain standards. This process relies on good inter-rater agreement on image assessment. We describe the Australian approach to NT image assessment and evaluate the impact of a targeted intervention on inter-rater agreement. Methods: Between 2002 and 2008 a group of experienced practitioners met nine times to compare their assessment of a series of NT images. Each assessor had previously scored the images according to a system described in 2002. Inter-rater agreement was evaluated before and after an intervention where the assessors were required to refer to a detailed resource manual designed to reduce the subjectivity inherent in image assessment. Results: There was a statistical improvement in inter-rater agreement for all elements of image assessment ...
Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, 2021
Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents a... more Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.
Objectives: The fetal adrenal gland receives rising awareness as a predictor of spontaneous prete... more Objectives: The fetal adrenal gland receives rising awareness as a predictor of spontaneous preterm birth. As previous studies focused on cross-sectional assessments, the aim of the present study was to provide longitudinal assessments of the fetal adrenal gland in a low risk population with an additional focus on growth-trajectories in fetuses born preterm. Methods: Analyses were based on data from a population-based low-risk prospective pregnancy cohort situated in Hamburg, Germany. Fetal adrenal gland was assessed via transabdominal ultrasound at gestational weeks (gw) 24-26, 28-30, and 34-36. Longitudinal trajectories of the total adrenal gland and the adrenal mark (so called fetal zone) as well as ratio of fetal zone width/ total adrenal gland widths (w/W) were analysed using repeated measurements ANOVA. To compare trajectories of the ratio w/W for fetuses preterm and term as well as women with and without clinical signs of preterm labour we additionally used the propensity score method. Results: Regarding total adrenal gland, longitudinal trajectories indicated a statistically significant increase for adrenal length, width, and volume (p < 0.0001) for those women with available measures at all three timepoints (n=386). Likewise, the fetal zone width increased over the course of pregnancy (p < 0.0001), while the ratio w/W decreased (p < 0.0001) (n= 329). Comparing the trajectories of the ratio w/W in fetuses born preterm (n=11) with propensity-score matched term born fetuses (n=22), a decrease between gw 24-26 and 28-30 was observed in both groups, which continued to decrease for the term born fetuses. However, in preterm born fetuses, the ratio increased above the term born values at gw 34-36. Conclusions: Our study provides longitudinal growth data on the fetal adrenal gland and supports the hypothesis that fetal zone enlargement is associated with preterm birth which could play an important role in risk-prediction. OP08.11 Uterine artery pulsatility index assessment < 11 weeks of gestation: a prospective study
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 26, 2016
The inclusion of the three vessel tracheal view (3VTV) in routine assessment of the fetal heart a... more The inclusion of the three vessel tracheal view (3VTV) in routine assessment of the fetal heart at the 18-20 week morphology scan improves recognition of a right-sided aortic arch (RAA). We report our experience of RAA diagnosed in an unselected population of women attending for a routine morphology scan. The obstetric imaging databases were reviewed retrospectively to identify all routine fetal morphology scans performed at 18-22 weeks' gestation between January 2011 and December 2014. A postnatal chart review was conducted to record findings at birth, neonatal complications and the anatomical findings at any neonatal echocardiographic or surgical procedure. The parents of older infants were also contacted by phone to assess their wellbeing and identify any respiratory or feeding difficulties. 43,083 routine anomaly scans were performed during this 48 month period. 23 cases of an isolated RAA was identified; a prevalence of 0.05%. 19 (83%) cases of isolated RAA had a left sided...
BJOG: An International Journal of Obstetrics & Gynaecology, 2015
The Australian healthcare system is complex. It involves both private and public providers with p... more The Australian healthcare system is complex. It involves both private and public providers with part-federal, part-state public funding and aims to offer high quality services in both metropolitan and rural/remote communities. Clinicians working in the state of Victoria have always been quick to adopt innovative methods for Down syndrome screening. Hui et al. report rates and results of prenatal invasive testing over a 38-year period. This program has seen a steady increase in detection of aneuploid fetuses and a reduction in the rate of invasive testing. Changes in screening policy, initially based on advanced maternal age, then on second trimester serum screening, most recently on combined first trimester screening, have led to a significant improvement in positive predictive value. These data are consistent with those described by Ekelund et al. (BMJ 2008;337:a2547 and Acta Obstet Gynecol Scand 2015;94:57–83), who reported a 50% reduction in live-born prevalence of Down syndrome and 50% reduction in invasive testing after the introduction of combined first trimester screening throughout Denmark. Assuming a prevalence of 1:500, the reported sensitivity (90%) of screening in this population essentially means that for every 5000 women screened, there will be one false negative result for Down syndrome. Although cell-free fetal DNA (cffDNA) screening is not currently publicly funded, it is readily available in Australia and the dynamics of the public–private system have seen rapid uptake. Hui et al. state that 1100 women had this test in Victoria in 2013 and found a high positive predictive value (82.8%) for this test. Although this may be distorted by the fact that cffDNA was initially often offered as an alternative to invasive testing for women who had a high-risk first or second trimester screen, it is consistent with the efficacy recently described in a low-risk population. Norton et al. (NEJM 2015;372:1589– 97) found sensitivity, specificity and positive predictive values for cffDNA detection of Down syndrome of 100, 0.06 and 80.9%, respectively. If further improvement in the predictive value of aneuploidy screening is important, then we should abandon current policies in favour of cffDNA testing. The test will not replace ultrasound, which will be needed to date the pregnancy, determine viability and number of fetuses, and exclude major lethal structural anomalies (such as anencephaly) before cffDNA screening. There will be continued value in assessing nuchal translucency, an indicator of atypical chromosomal abnormalities not currently detected by cffDNA testing (Petersen et al. Ultrasound Obstet Gynecol 2014;43:265–71). cffDNA will therefore be an additional screening tool, with significant additional cost to detect one Down pregnancy in every 5000 women screened. Broadly speaking, the methodological changes in screening for Down syndrome described by Hui et al. can be applied to other adverse obstetric outcomes and therapeutic interventions may be useful if risk is identified at an early gestation (Park et al. Ultrasound Obstet Gynecol 2015;46;419–423). Hopefully policy makers will see the value of letting us have our cake and eating it.
Best practice & research. Clinical obstetrics & gynaecology, 2015
A number of groups are currently examining the potential of screening for pre-eclampsia and gesta... more A number of groups are currently examining the potential of screening for pre-eclampsia and gestational diabetes at 12 weeks' gestation. This can be performed at the time of combined first-trimester screening for aneuploidy using a similar method of regression analysis to combine multiple demographic and investigative factors. At present, research into the prediction of pre-eclampsia is more robust and is associated with the potential for therapeutic intervention that can reduce the prevalence of early-onset pre-eclampsia and improve maternal and neonatal outcomes.
Objective To assess differences in adipose deposition in fetuses from normal pregnancies and wom... more Objective To assess differences in adipose deposition in fetuses from normal pregnancies and women with diabetes.
OBJECTIVES Preeclampsia causes substantial maternal and neonatal mortality and morbidity. In addi... more OBJECTIVES Preeclampsia causes substantial maternal and neonatal mortality and morbidity. In addition to a personal impact on women, children and their families, preeclampsia has a significant economic impact on our society. Recent research suggests that a first trimester multivariate model is highly predictive of preterm (<37 weeks' gestation) preeclampsia and can be successfully combined with targeted prophylaxis (low dose aspirin) with 80% reduction in prevalence of disease. We examined the potential health outcomes and cost implications following introduction of first trimester prediction and prevention of preterm preeclampsia within a public healthcare setting when compared to Usual Care and conducted a cost-effectiveness analysis that informs health service decisions regarding implementation of such a program. METHODS A decision analytic model was used to compare Usual Care to the proposed first trimester screening intervention within the obstetric population (n=6,822) attending two public hospitals within a metropolitan district health service in New South Wales, Australia between January 2015 and December 2016. The model worked from early pregnancy, included exposure to a variety of healthcare professionals, addressed exposure to risk assessment (Usual Care or first trimester screening) and use / compliance with low dose aspirin prescribed prophylactically for prevention of preeclampsia. All pathways culminated in six possible health outcomes ranging from no preeclampsia to maternal death. Results were presented as the number of cases of preeclampsia gained/avoided and the incremental increase/decrease in economic costs arising from the Intervention compared to Usual Care. Significant assumptions were tested in sensitivity/uncertainty analyses. RESULTS The intervention produced, across all gestational ages, 31 fewer cases of preeclampsia and reduced aggregate economic health service costs by $1,431,186 over this two-year period. None of the tested iterations of uncertainty analyses reported additional cases of preeclampsia or higher economic costs. The new intervention based on first trimester screening dominated Usual Care. CONCLUSION This cost effectiveness analysis demonstrates a reduction in prevalence of preterm preeclampsia and substantial cost savings associated with a population based program of first trimester prediction and prevention of preeclampsia and provides support for implementation of such a policy. This article is protected by copyright. All rights reserved.
<b><i>Objective:</i></b> The study aimed to investigate the association b... more <b><i>Objective:</i></b> The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. <b><i>Methods:</i></b> We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. <b><i>Results:</i></b> The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (&lt;0.3 MoM and &lt;0.5 MoM) were independently associated with sPTB, low BW, PE, GH, and a composite adverse pregnancy outcome score, with odds ratios between 1.81 and 4.44 on multivariable logistic regression analyses. <b><i>Conclusions:</i></b> Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.
Australasian Journal of Ultrasound in Medicine, 2017
The placenta is the link between mother and fetus and its function is central to a successful pre... more The placenta is the link between mother and fetus and its function is central to a successful pregnancy. The predominant theory within the literature is that the development of placental dysfunction is a result of abnormal trophoblast invasion early in pregnancy. Knowledge of the development of the early placenta and the establishment of the fetomaternal circulation assists in understanding the origins of placental dysfunction which manifest later in pregnancy.Perinatally, chronic placental dysfunction may result in a growth‐restricted fetus, maternal problems such as gestational hypertension, pre‐eclampsia, eclampsia and pregnancy complications such as placental abruption, preterm labour and delivery. In addition, the growth‐restricted fetus and the mother are at an increased risk of a myriad of disorders later in life.The role of ultrasound in the assessment of first trimester pregnancy is evolving with the potential for value in the prediction of placental function in later pregn...
Introduction: Standardization of first-trimester nuchal translucency (NT) image acquisition is cr... more Introduction: Standardization of first-trimester nuchal translucency (NT) image acquisition is crucial to the success of screening for Down syndrome. Rigorous audit of operator performance and constructive feedback from assessors maintain standards. This process relies on good inter-rater agreement on image assessment. We describe the Australian approach to NT image assessment and evaluate the impact of a targeted intervention on inter-rater agreement. Methods: Between 2002 and 2008 a group of experienced practitioners met nine times to compare their assessment of a series of NT images. Each assessor had previously scored the images according to a system described in 2002. Inter-rater agreement was evaluated before and after an intervention where the assessors were required to refer to a detailed resource manual designed to reduce the subjectivity inherent in image assessment. Results: There was a statistical improvement in inter-rater agreement for all elements of image assessment ...
Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, 2021
Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents a... more Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.
Objectives: The fetal adrenal gland receives rising awareness as a predictor of spontaneous prete... more Objectives: The fetal adrenal gland receives rising awareness as a predictor of spontaneous preterm birth. As previous studies focused on cross-sectional assessments, the aim of the present study was to provide longitudinal assessments of the fetal adrenal gland in a low risk population with an additional focus on growth-trajectories in fetuses born preterm. Methods: Analyses were based on data from a population-based low-risk prospective pregnancy cohort situated in Hamburg, Germany. Fetal adrenal gland was assessed via transabdominal ultrasound at gestational weeks (gw) 24-26, 28-30, and 34-36. Longitudinal trajectories of the total adrenal gland and the adrenal mark (so called fetal zone) as well as ratio of fetal zone width/ total adrenal gland widths (w/W) were analysed using repeated measurements ANOVA. To compare trajectories of the ratio w/W for fetuses preterm and term as well as women with and without clinical signs of preterm labour we additionally used the propensity score method. Results: Regarding total adrenal gland, longitudinal trajectories indicated a statistically significant increase for adrenal length, width, and volume (p < 0.0001) for those women with available measures at all three timepoints (n=386). Likewise, the fetal zone width increased over the course of pregnancy (p < 0.0001), while the ratio w/W decreased (p < 0.0001) (n= 329). Comparing the trajectories of the ratio w/W in fetuses born preterm (n=11) with propensity-score matched term born fetuses (n=22), a decrease between gw 24-26 and 28-30 was observed in both groups, which continued to decrease for the term born fetuses. However, in preterm born fetuses, the ratio increased above the term born values at gw 34-36. Conclusions: Our study provides longitudinal growth data on the fetal adrenal gland and supports the hypothesis that fetal zone enlargement is associated with preterm birth which could play an important role in risk-prediction. OP08.11 Uterine artery pulsatility index assessment < 11 weeks of gestation: a prospective study
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 26, 2016
The inclusion of the three vessel tracheal view (3VTV) in routine assessment of the fetal heart a... more The inclusion of the three vessel tracheal view (3VTV) in routine assessment of the fetal heart at the 18-20 week morphology scan improves recognition of a right-sided aortic arch (RAA). We report our experience of RAA diagnosed in an unselected population of women attending for a routine morphology scan. The obstetric imaging databases were reviewed retrospectively to identify all routine fetal morphology scans performed at 18-22 weeks' gestation between January 2011 and December 2014. A postnatal chart review was conducted to record findings at birth, neonatal complications and the anatomical findings at any neonatal echocardiographic or surgical procedure. The parents of older infants were also contacted by phone to assess their wellbeing and identify any respiratory or feeding difficulties. 43,083 routine anomaly scans were performed during this 48 month period. 23 cases of an isolated RAA was identified; a prevalence of 0.05%. 19 (83%) cases of isolated RAA had a left sided...
BJOG: An International Journal of Obstetrics & Gynaecology, 2015
The Australian healthcare system is complex. It involves both private and public providers with p... more The Australian healthcare system is complex. It involves both private and public providers with part-federal, part-state public funding and aims to offer high quality services in both metropolitan and rural/remote communities. Clinicians working in the state of Victoria have always been quick to adopt innovative methods for Down syndrome screening. Hui et al. report rates and results of prenatal invasive testing over a 38-year period. This program has seen a steady increase in detection of aneuploid fetuses and a reduction in the rate of invasive testing. Changes in screening policy, initially based on advanced maternal age, then on second trimester serum screening, most recently on combined first trimester screening, have led to a significant improvement in positive predictive value. These data are consistent with those described by Ekelund et al. (BMJ 2008;337:a2547 and Acta Obstet Gynecol Scand 2015;94:57–83), who reported a 50% reduction in live-born prevalence of Down syndrome and 50% reduction in invasive testing after the introduction of combined first trimester screening throughout Denmark. Assuming a prevalence of 1:500, the reported sensitivity (90%) of screening in this population essentially means that for every 5000 women screened, there will be one false negative result for Down syndrome. Although cell-free fetal DNA (cffDNA) screening is not currently publicly funded, it is readily available in Australia and the dynamics of the public–private system have seen rapid uptake. Hui et al. state that 1100 women had this test in Victoria in 2013 and found a high positive predictive value (82.8%) for this test. Although this may be distorted by the fact that cffDNA was initially often offered as an alternative to invasive testing for women who had a high-risk first or second trimester screen, it is consistent with the efficacy recently described in a low-risk population. Norton et al. (NEJM 2015;372:1589– 97) found sensitivity, specificity and positive predictive values for cffDNA detection of Down syndrome of 100, 0.06 and 80.9%, respectively. If further improvement in the predictive value of aneuploidy screening is important, then we should abandon current policies in favour of cffDNA testing. The test will not replace ultrasound, which will be needed to date the pregnancy, determine viability and number of fetuses, and exclude major lethal structural anomalies (such as anencephaly) before cffDNA screening. There will be continued value in assessing nuchal translucency, an indicator of atypical chromosomal abnormalities not currently detected by cffDNA testing (Petersen et al. Ultrasound Obstet Gynecol 2014;43:265–71). cffDNA will therefore be an additional screening tool, with significant additional cost to detect one Down pregnancy in every 5000 women screened. Broadly speaking, the methodological changes in screening for Down syndrome described by Hui et al. can be applied to other adverse obstetric outcomes and therapeutic interventions may be useful if risk is identified at an early gestation (Park et al. Ultrasound Obstet Gynecol 2015;46;419–423). Hopefully policy makers will see the value of letting us have our cake and eating it.
Best practice & research. Clinical obstetrics & gynaecology, 2015
A number of groups are currently examining the potential of screening for pre-eclampsia and gesta... more A number of groups are currently examining the potential of screening for pre-eclampsia and gestational diabetes at 12 weeks' gestation. This can be performed at the time of combined first-trimester screening for aneuploidy using a similar method of regression analysis to combine multiple demographic and investigative factors. At present, research into the prediction of pre-eclampsia is more robust and is associated with the potential for therapeutic intervention that can reduce the prevalence of early-onset pre-eclampsia and improve maternal and neonatal outcomes.
Objective To assess differences in adipose deposition in fetuses from normal pregnancies and wom... more Objective To assess differences in adipose deposition in fetuses from normal pregnancies and women with diabetes.
OBJECTIVES Preeclampsia causes substantial maternal and neonatal mortality and morbidity. In addi... more OBJECTIVES Preeclampsia causes substantial maternal and neonatal mortality and morbidity. In addition to a personal impact on women, children and their families, preeclampsia has a significant economic impact on our society. Recent research suggests that a first trimester multivariate model is highly predictive of preterm (<37 weeks' gestation) preeclampsia and can be successfully combined with targeted prophylaxis (low dose aspirin) with 80% reduction in prevalence of disease. We examined the potential health outcomes and cost implications following introduction of first trimester prediction and prevention of preterm preeclampsia within a public healthcare setting when compared to Usual Care and conducted a cost-effectiveness analysis that informs health service decisions regarding implementation of such a program. METHODS A decision analytic model was used to compare Usual Care to the proposed first trimester screening intervention within the obstetric population (n=6,822) attending two public hospitals within a metropolitan district health service in New South Wales, Australia between January 2015 and December 2016. The model worked from early pregnancy, included exposure to a variety of healthcare professionals, addressed exposure to risk assessment (Usual Care or first trimester screening) and use / compliance with low dose aspirin prescribed prophylactically for prevention of preeclampsia. All pathways culminated in six possible health outcomes ranging from no preeclampsia to maternal death. Results were presented as the number of cases of preeclampsia gained/avoided and the incremental increase/decrease in economic costs arising from the Intervention compared to Usual Care. Significant assumptions were tested in sensitivity/uncertainty analyses. RESULTS The intervention produced, across all gestational ages, 31 fewer cases of preeclampsia and reduced aggregate economic health service costs by $1,431,186 over this two-year period. None of the tested iterations of uncertainty analyses reported additional cases of preeclampsia or higher economic costs. The new intervention based on first trimester screening dominated Usual Care. CONCLUSION This cost effectiveness analysis demonstrates a reduction in prevalence of preterm preeclampsia and substantial cost savings associated with a population based program of first trimester prediction and prevention of preeclampsia and provides support for implementation of such a policy. This article is protected by copyright. All rights reserved.
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