Term PE Research Articles

Prediction model of preeclampsia using machine learning based methods: a population based cohort study in China.

Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of high-risk groups for preeclampsia and timely intervention with aspirin is an effective preventive method against preeclampsia. This study aims to develop a robust and effective preeclampsia prediction model with good performance by machine learning algorithms based on maternal characteristics, biophysical and biochemical markers at 11-13+6 weeks' gestation, providing an effective tool for early screening and prediction of preeclampsia. This study included 5116 singleton pregnant women who underwent PE screening and fetal aneuploidy from a prospective cohort longitudinal study in China. Maternal characteristics (such as maternal age, height, pre-pregnancy weight), past medical history, mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A, and placental growth factor were collected as the covariates for the preeclampsia prediction model. Five classification algorithms including Logistic Regression, Extra Trees Classifier, Voting Classifier, Gaussian Process Classifier and Stacking Classifier were applied for the prediction model development. Five-fold cross-validation with an 8:2 train-test split was applied for model validation. We ultimately included 49 cases of preterm preeclampsia and 161 cases of term preeclampsia from the 4644 pregnant women data in the final analysis. Compared with other prediction algorithms, the AUC and detection rate at 10% FPR of the Voting Classifier algorithm showed better performance in the prediction of preterm preeclampsia (AUC=0.884, DR at 10%FPR=0.625) under all covariates included. However, its performance was similar to that of other model algorithms in all PE and term PE prediction. In the prediction of all preeclampsia, the contribution of PLGF was higher than PAPP-A (11.9% VS 8.7%), while the situation was opposite in the prediction of preterm preeclampsia (7.2% VS 16.5%). The performance for preeclampsia or preterm preeclampsia using machine learning algorithms was similar to that achieved by the fetal medicine foundation competing risk model under the same predictive factors (AUCs of 0.797 and 0.856 for PE and preterm PE, respectively). Our models provide an accessible tool for large-scale population screening and prediction of preeclampsia, which helps reduce the disease burden and improve maternal and fetal outcomes.

Blood pressure cutoffs at 11–13 weeks of gestation and risk of preeclampsia

A parallel has been drawn between first-trimester placental vascular maturation and maternal cardiovascular adaptations, including blood pressure. Although 140/90 mm Hg is well-accepted as the threshold for chronic hypertension in the general obstetric population in early pregnancy, a different threshold could apply to stratify the risk of adverse outcomes, such as preeclampsia. This could have implications for interventions, such as the threshold for initiation of antihypertensive therapy and the target blood pressure level. We evaluated the relationship between various blood pressure cutoffs at 11-13 weeks of gestation and the development of preeclampsia, overall and according to key maternal characteristics. This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals, 2006-2020. Blood pressure at 11-13 weeks of gestation was classified according to American College of Cardiology/American Heart Association categories (mm Hg) as (1) normal blood pressure (systolic <120 and diastolic <80), (2) elevated blood pressure (systolic ≥120 and diastolic <80), stage 1 hypertension (systolic ≥130 or diastolic 80-89), and stage 2 hypertension (systolic ≥140 or diastolic ≥90). For blood pressure category thresholds and the outcome of preeclampsia, the following were calculated overall and across maternal age, body mass index, ethnicity, method of conception, and previous pregnancy history: detection rate, screen-positive rate, and positive and negative likelihood ratios, with 95% confidence intervals. A P value of <.05 was considered significant. There were 137,458 pregnancies screened at 11-13 weeks of gestation. The population was ethnically diverse, with 15.9% of Black ethnicity, 6.7% of South or East Asian ethnicity, and 2.7% of mixed ethnicity, with the remainder of White ethnicity. Compared with normal blood pressure, stage 2 hypertension was associated with both preterm preeclampsia (0.3% to 4.9%) and term preeclampsia (1.0% to 8.3%). A blood pressure threshold of 140/90 mm Hg was good at identifying women at increased risk of preeclampsia overall (positive likelihood ratio, 5.61 [95% confidence interval, 5.14-6.11]) and across maternal characteristics, compared with elevated blood pressure (positive likelihood ratio, 1.70 [95% confidence interval, 1.63-1.77]) and stage 1 hypertension (positive likelihood ratio, 2.68 [95% confidence interval, 2.58-2.77]). There were 2 exceptions: a blood pressure threshold of 130/80 mm Hg was better for the 2.1% of women with body mass index <18.5 kg/m2 (positive likelihood ratio, 5.13 [95% confidence interval, 3.22-8.16]), and a threshold of 135/85 mm Hg better for the 50.4% of parous women without a history of preeclampsia (positive likelihood ratio, 5.24, [95% confidence interval, 4.77-5.77]). There was no blood pressure threshold below which reassurance could be provided against the development of preeclampsia (all-negative likelihood ratios ≥0.20). The traditional blood pressure threshold of 140/90 mm Hg performs well to identify women at increased risk of preeclampsia. Women who are underweight or parous with no prior history of preeclampsia may be better identified by lower thresholds; however, a randomized trial would be necessary to determine any benefits of such an approach if antihypertensive therapy were also administered at this threshold. No blood pressure threshold is reassured against the development of preeclampsia, regardless of maternal characteristics.

First Trimester Preeclampsia Screening and Prevention: Perspective in Chinese Mainland

Abstract Preeclampsia (PE), a multisystem disorder in pregnancy, is one of the leading causes of perinatal morbidity and mortality that poses financial and physical burdens worldwide. Preterm PE with delivery at &lt;37 weeks of gestation is associated with a higher risk of adverse maternal and perinatal outcomes than term PE with delivery at ≥37 weeks of gestation. A myriad of first trimester screening models have been developed to identifying women at risk of preterm PE. In fact, the Fetal Medicine Foundation (FMF) first trimester prediction model has undergone successful internal and external validation. The FMF triple test enables the estimation of patient-specific risks, using Bayes theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor. Establishing a quality control process for regular monitoring and to ensure data standardization, reliability, and accuracy is key to maintaining optimal screening performance. The rate of preterm PE can be reduced by 62% by using the FMF prediction model, followed by the administration of low-dose aspirin. Recent evidence has also demonstrated that metformin has the potential for preventing PE in patients at high-risk of the disorder. In this article, we will summarize the existing literature on the different screening methods, different components of risk assessment, therapeutic interventions, and clinical implementation of the first trimester screening and prevention program for PE with specific considerations for Chinese mainland.

Chitosan/alginate dialdehyde trilayer films with cinnamaldehyde nanoemulsions for grass carp preservation

Chitosan (CS) cross-linked films were prepared using the Maillard reaction (CMR). Layer-by-layer casting created additional layers using alginate dialdehyde (ADA) containing cinnamaldehyde nanoemulsions (CANE) and CS. The ability to preserve grass carp fillets was evaluated along with the effects of CANE concentration on the microstructure, physicochemical properties, controlled-release behavior, antioxidation, and antibacterial activities of the films. In all films, Schiff base-induced bonds, electrostatic interactions, and hydrogen bonds brought the layers closer together, improving the mechanical properties (e.g., a 70% increase in tensile strength and a 34% increase in breaking elongation) and barrier capacity (e.g., inhibiting ultraviolet, water vapor, and oxygen transmission). CANE can improve the antioxidant activity, antibacterial activity, and sustained release characteristics of films. More importantly, over the 8-day storage period, the fish packaged using the active films were better than those in the control, commercial PE, and CS films in terms of thiobarbituric acid reactive substances, pH, texture, total viable counts, and volatile basic nitrogen with indicator species. Fish could have a prolonged shelf life due to the prepared CMR/ADA-CA/CS film. In other words, it may be used as a sustainable food packaging material, with the performance of the film being regulated by different CANE concentrations.

Independent predictors of preeclampsia and their impact on the complication in Bulgarian study group of pregnant women.

One of the major obstetrical complications, affecting 2%-8% of all pregnancies, is preeclampsia. To predict the onset of preeclampsia, several methods have recently been put forth. The Fetal Medicine Foundation has developed combined screening that can identify the vast majority of women who will develop preeclampsia using a combination of maternal factors, obstetrical history, biochemical, and biophysical factors.

P-784 First trimester screening for preterm preeclampsia after ART: high risk, high gain?

Abstract Study question What is the preterm preeclampsia (pPE) incidence in selected high-risk ART patient populations when applying a first trimester screening approach to recommend prevention via aspirin? Summary answer One in five high-risk ART patients had a calculated risk &amp;gt;1/100 and despite aspirin prophylaxis still 22.2% of them developed pPE. What is known already Preeclampsia (PE) is an obstetrical complication defined by new-onset hypertension after 20 weeks’ gestation with proteinuria, end-organ (including placental) dysfunction or both. First trimester pPE screening is gaining ground in prenatal care since a study on approximately 60.000 singleton pregnancies reported an algorithm able to detect 76% of pPE and 38% of term PE (tPE). A RCT showed that aspirin, prescribed upon positive screening, led to an effective (62%) reduction of pPE incidence. This screening/prevention strategy has not been validated in the context of ART pregnancies, while some ART patient groups are known to be at higher risk for PE. Study design, size, duration This is a retrospective, single-center, observational cohort study, including 242 patients between 18 and 48 years old, pregnant after ART and considered at higher risk of PE because of one of the following characteristics: diagnosed with polycystic ovary syndrome (PCOS), being an oocyte recipient (OR) or pregnant from a frozen embryo transfer in an artificially prepared cycle (HRT-FET). Patients were included from May 2021 until July 2022. Participants/materials, setting, methods Screening was systematically offered between 11-14 weeks’ gestation, according to the Fetal Medicine Foundation (FMF) algorithm including maternal factors, mean arterial pressure, uterine arteries pulsatility index and serum placental growth factor. If the risk of developing PE was &amp;gt;1/100, administration of 160mg aspirin was started until 36 weeks’ gestation. Primary outcome was the incidence of pPE(&amp;lt;37 weeks). Secondary outcomes were the incidence of tPE(≥37 weeks) and the incidence of positive first trimester screening (risk &amp;gt;1/100). Main results and the role of chance A total of 242 unique patients were screened: 58 oocyte recipients (ORs), 89 PCOS and 95 HRT-FET patients (the latter having no PCOS and using autologous oocytes). The overall positive screening incidence was 21.9%(53/242), with the highest positive screening rate in ORs (27.6%, 16/58). In PCOS and HRT-FET patients, we observed a positive screening test in 20.2%(18/89) and 20.0%(19/95), respectively. For comparison, the positive screening rate reported for the general population was 10.5%. Despite the prophylactic aspirin regimen started upon positive screening, in the current study an overall pPE incidence of 22.6%(12/53) was observed while the reported pPE incidence in the general population in this setting was only 1.6%. More specifically, 31.2%(5/16) ORs with positive screening developed pPE although they used aspirin. For PCOS and HRT-FET patients, this was 11.1%(2/18) and 21.1% (4/19), respectively. tPE occurred in 7.5%(4/53) of women with positive screening and aspirin intake (1/16 in ORs, 1/18 in PCOS patients and 2/19 following HRT-FET). For comparison, in the general population this was 6.7%. Following a negative first trimester screening test, 2.1%(4/189) of patients developed pPE and 3.7%(7/189) tPE. In a non-selected population, these incidences have been reported to be 0.2% and 1.1%, respectively. Limitations, reasons for caution This study is limited by its retrospective study design, small sample size and observational nature. Nevertheless, it is of major importance to communicate the strikingly high pPE incidences in specific subtypes of ART patients despite first trimester screening and aspirin prophylaxis. Wider implications of the findings Our findings suggest that current screening algorithms are not optimized for women pregnant following ART. In pregnancies from oocyte donation, aspirin might be less effective. Future research should aim at finetuning PE screening methods specifically for ART patients and differential mechanisms of PE origin need to be further investigated. Trial registration number Not applicable

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis.

Small-cell lung cancer (SCLC) has a poor prognosis. For the last 30 years, first-line systemic treatment has remained unaltered. After the integration of ımmunotherapy, a new first-line gold standard, atezolizumab in combination with carboplatin plus etoposide, was approved in extensive-disease SCLC (ED-SCLC) in 2019. First-line randomized controlled studies that investigated anti-programmed cell death protein 1 (PD-1)/PD-1 ligand-1 (PD-L1) and anti-T-lymphocyte-associated protein 4 (CTLA-4) agents in combination with platinum plus etoposide (EP) were scoured. A total of six studies (two - anti-CTLA-4 and four - anti-PD1/PD-L1) were included and classic and network meta-analyses (NMAs) were performed. Fixed model for overall survival (OAS) in the PD-1- or PD-L1-treated subgroup yielded a hazard ratio (HR) of 0.746 with a 95% confidence interval (CI) =0.662-0.840 and in the CTLA-4-treated subgroup a HR of 0.941 with a 95% CI = 0.816-1.084 for the immune therapy + chemotherapy versus chemotherapy comparison (CTLA-4-based versus PD-1- or PD-L1-based groups' comparison of OAS effect Q = 6.05, df = 1, P = 0.014). NMA showed that all chemotherapy + immunotherapy combinations were equally potent and more efficient than PE in terms of OAS and progression-free survival (PFS). Rank probability plots demonstrated nivolumab + EP as the most probable effective treatment modality in terms of OAS and PFS. The usage of anti-PD1/PD-L1 immunotherapy agents results in significant OAS advantage, and anti-PD1/PD-L1 agents are superior to anti-CTLA-4 approach in combination with platinum plus etoposide regimen in ED-SCLC.

Relationship between the pre-pregnancy BMI, gestational weight gain, and risk of preeclampsia and its subtypes

Objective: To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia. Methods: Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes. Results: Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension (P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m2 and inadequate gestational weight gain were protective factors for PE (OR=0.74, 95%CI: 0.56-0.98; OR=0.78, 95%CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m2 and excessive gestational weight gain were risk factors for PE (OR=1.82, 95%CI: 1.54-2.14; OR=1.82, 95%CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m2 was a protective factor for EOPE and MPE (OR=0.52, 95%CI: 0.32-0.83; OR=0.47, 95%CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE (OR=1.86, 95%CI: 1.51-2.30; OR=1.90, 95%CI: 1.39-2.60) in pregnant women 18.5 kg/m2≤BMI<24.0 kg/m2 and ≥24.0 kg/m2. Inadequate gestational weight gain (OR=0.55, 95%CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m2. Excessive gestational weight gain (OR=4.05, 95%CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m2≤BMI<24.0 kg/m2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE (OR=0.39, 95%CI: 0.19-0.80; OR=0.29, 95%CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE (OR=1.60, 95%CI: 1.06-2.42;OR=2.20, 95%CI: 1.44-3.37;OR=2.28, 95%CI: 1.58-3.29). Conclusions: Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.

The effect of the variability of wind forcing on ENSO simulation in an OGCM: case of canonical and protracted event

This study is an attempt to understand the onset and the evolution of canonical (typical length ~ 18–24 months; CE) and protracted El Niño (> greater than 3 years; PE) compared to the normal state (NS) in an ocean model. Indo-Pacific warm pool indicates higher sea surface temperature (SST) before the onset of strong CE compared to the NS and PE. The ocean model (MOM5.1.0) used in the study shows a systematic SST bias in the Indo-Pacific Ocean with warmer (cooler) temperatures in the western (eastern) Pacific during NS, CE, and PE exhibiting La Niña–like conditions. The model also exhibits deeper thermocline depth in the western equatorial Pacific Ocean during PE and CE than NS, indicating higher heat content values. Despite higher heat content in the western Pacific before the onset of El Niño, the difference in the variability of surface wind forcing during the preceding months determines the type of El Niño. The difference in surface wind forcing among the NS, PE, and CE states without altering the ocean state can modify the subsurface propagation in the equatorial Pacific Ocean. A change in longitudinal extent of upwelling Kelvin waves from western Pacific towards eastern Pacific along with the change in surface wind forcing decides the fate of El Niño. Based on the results of model experiments for 1948–2009, observed features of the recent protracted El Niño of 2014–2016 appear to be a blend of PE and CE in terms of ocean dynamics and surface wind forcing.

First Trimester Screening for Preeclampsia: An Asian Perspective

AbstractPreeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. This disorder has profound short-term and long-term impacts on both the affected woman's and her child's health. Early-onset PE requiring preterm delivery (preterm PE) is of particular importance because it is associated with a higher risk of adverse pregnancy outcomes than term PE. First trimester screening model developed by the Fetal Medicine Foundation (FMF), which uses Bayes-theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has been proven to be effective and have superior screening performance to that of traditional risk factor-based approach for the prediction of PE. Identification of high risk pregnant women for preterm PE and giving aspirin prophylaxis before 16thweek of gestation would reduce the incidence of preterm PE. In Asia, although the prevalence of PE is slightly lower than the global estimation, early screening and prevention of this life-threatening condition is still crucial. The FMF Bayes-theorem based screening method has been validated in a large-scale prospective Asia-wide study and revealed that the first trimester triple test achieves the highest detection rate, compared with the traditional risk factor-based approaches, and that the screening performance is comparable to the published data from the FMF in East Asian women. However, in order to achieve optimal screening performance, the key is to establish standardized methods for biomarker measurements and regular biomarker quality assessment, as each biomarker is susceptible to inaccurate measurement, thus affecting performance of screening. Furthermore, it is of great importance to emphasize that the optimal preventive effect of aspirin on preterm PE is clearly associated with good compliance to treatment. In conclusion, global implementation of an effective first trimester “screen and prevent” program for preterm PE would provide the opportunity to reduce the risk of both short-term maternal and perinatal morbidity and mortality, with the possibility of intergenerational prevention of future chronic diseases for both the mother and her offspring.

MOC-Z Models for Transient Gaseous Cavitation in Pipe Flow

AbstractThe paper presents models based on the method of characteristics (MOC) for transient gaseous cavitation in pipe flow. Two predictor-corrector steps are considered, in which only the term pe...

Screening and Prevention of Preeclampsia

Abstract Preeclampsia (PE) is a multisystem disorder of pregnancy classically characterized by hypertension with significant proteinuria after 20 weeks’ gestation. This disorder is one of the leading causes of maternal and perinatal morbidity and mortality. PE can be subdivided into preterm PE (with delivery at &lt;37 weeks’ gestation) and term PE (with delivery at ≥37 weeks’ gestation). Preterm PE is associated with a higher risk of adverse maternal and perinatal outcomes than term PE. Traditional method of screening as recommended by professional guidelines has limited predictive performance and therefore should be updated to reflect recent scientific evidence that the target of screening should be preterm PE, the best way to identify the high-risk group is the Bayes-based method that combines maternal risk factors and biomarkers, the threshold should be set at screen positive rate of 10%, aspirin should be started before 16 weeks’ gestation, and the daily dose should be higher than 100 mg.

Mechanistic insight in the selective delignification of wheat straw by three white-rot fungal species through quantitative 13C-IS py-GC\u2013MS and whole cell wall HSQC NMR

BackgroundThe white-rot fungi Ceriporiopsis subvermispora (Cs), Pleurotus eryngii (Pe), and Lentinula edodes (Le) have been shown to be high-potential species for selective delignification of plant biomass. This delignification improves polysaccharide degradability, which currently limits the efficient lignocellulose conversion into biochemicals, biofuels, and animal feed. Since selectivity and time efficiency of fungal delignification still need optimization, detailed understanding of the underlying mechanisms at molecular level is required. The recently developed methodologies for lignin quantification and characterization now allow for the in-depth mapping of fungal modification and degradation of lignin and, thereby, enable resolving underlying mechanisms.ResultsWheat straw treated by two strains of Cs (Cs1 and Cs12), Pe (Pe3 and Pe6) and Le (Le8 and Le10) was characterized using semi-quantitative py-GC–MS during fungal growth (1, 3, and 7 weeks). The remaining lignin after 7 weeks was quantified and characterized using 13C lignin internal standard based py-GC–MS and whole cell wall HSQC NMR. Strains of the same species showed similar patterns of lignin removal and degradation. Cs and Le outperformed Pe in terms of extent and selectivity of delignification (Cs ≥ Le >> Pe). The highest lignin removal [66% (w/w); Cs1] was obtained after 7 weeks, without extensive carbohydrate degradation (factor 3 increased carbohydrate-to-lignin ratio). Furthermore, though after treatment with Cs and Le comparable amounts of lignin remained, the structure of the residual lignin vastly differed. For example, Cα-oxidized substructures accumulated in Cs treated lignin up to 24% of the total aromatic lignin, a factor two higher than in Le-treated lignin. Contrarily, ferulic acid substructures were preferentially targeted by Le (and Pe). Interestingly, Pe-spent lignin was specifically depleted of tricin (40% reduction). The overall subunit composition (H:G:S) was not affected by fungal treatment.ConclusionsCs and Le are both able to effectively and selectively delignify wheat straw, though the underlying mechanisms are fundamentally different. We are the first to identify that Cs degrades the major β-O-4 ether linkage in grass lignin mainly via Cβ–O–aryl cleavage, while Cα–Cβ cleavage of inter-unit linkages predominated for Le. Our research provides a new insight on how fungi degrade lignin, which contributes to further optimizing the biological upgrading of lignocellulose.

Intensified Cold Pool Dynamics Under Stronger Surface Heating

AbstractThe observed increase of convective extreme precipitation intensities with temperature beyond the Clausius‐Clapeyron rate has recently directed attention to nonequilibrium processes that might cause the increase. While out‐of‐equilibrium simulations with perturbed heating conditions show clear increases in convective precipitation intensities, it has so far remained unclear, to which extent precipitation intensities can increase, when the atmosphere is in “perpetual equilibrium” (PE). We use the term PE to describe periodically forced diurnal cycles that eventually yield an approximately repetitive atmospheric response from day to day. In PE, as defined here, precipitation extremes increase at rates beyond the Clausius‐Clapeyron rate. When analyzing causes for the increase, we find the variance in near‐surface temperature to increase significantly as precipitation builds up throughout the day and that this temperature variance is larger when surface heating is increased. We propose that enhanced rain evaporation may drive a feedback, by which cold pool activity, and the possible collision of cold pool gust fronts, is strengthened—thereby intensifying subsequent convective updrafts and their precipitation.

Positional cloning of a Bombyx pink-eyed white egg locus reveals the major role of cardinal in ommochrome synthesis.

Ommochromes are major insect pigments involved in coloration of compound eyes, eggs, epidermis and wings. In the silkworm Bombyx mori, adult compound eyes and eggs contain a mixture of the ommochrome pigments such as ommin and xanthommatin. Here, we identified the gene involved in ommochrome biosynthesis by positional cloning of B. mori egg and eye color mutant pink-eyed white egg (pe). The recessive homozygote of pe has bright red eyes and white or pale pink eggs instead of a normal dark coloration due to the decrease of dark ommochrome pigments. By genetic linkage analysis, we narrowed down the pe-linked region to ~258 kb, containing 17 predicted genes. RNA sequencing analyses showed that the expression of one candidate gene, the ortholog of Drosophila haem peroxidase cardinal, coincided with egg pigmentation timing, similar to other ommochrome-related genes such as Bm-scarlet and Bm-re. In two pe strains, a common missense mutation was found within a conserved motif of B. mori cardinal homolog (Bm-cardinal). RNA interference-mediated knockdown and transcription activator-like effector nuclease (TALEN)-mediated knockout of the Bm-cardinal gene produced the same phenotype as pe in terms of egg, adult eye and larval epidermis coloration. A complementation test of the pe mutant with the TALEN-mediated Bm-cardinal-deficient strain showed that the mutant phenotype could not be rescued, indicating that Bm-cardinal is responsible for pe. Moreover, knockdown of the cardinal homolog in Tribolium castaneum also induced red compound eyes. Our results indicate that cardinal plays a major role in ommochrome synthesis of holometabolous insects.

Parental environmental effects due to contrasting watering adapt competitive ability, but not drought tolerance, in offspring of a semi‐arid annual Brassicaceae

Summary Parental effects (PE) can be adaptive and improve offspring performance when parents and offspring experience similar environmental conditions. However, it is unknown whether adaptive PE exist also in habitats where such similarity is unlikely due to strong temporal variation. In particular, we do not know whether PE can adapt offspring to fluctuating levels of neighbour competition in such habitats. Here, we tested for adaptive PE in terms of two key environmental factors in a semi‐arid annual system, competition and drought. While rainfall was stochastic in the study site, the competitive environment was partly predictable: higher plant densities followed after favourable (rainy) years due to high seed production. We therefore expected PE to adapt the offspring's competitive ability to these (predictable) fluctuations in plant densities, rather than to adapt the offspring's drought tolerance to the (unpredictable) occurrence of intensified drought. Parental plants of Biscutella didyma, an annual Brassicaceae, were raised under favourable watering and under drought conditions. Offspring performance was then tested under a full‐factorial combination of two neighbour regimes and six watering levels in the glasshouse. Offspring of parents grown under favourable conditions were stronger competitors. This was associated with a small shift in phenology but not with higher parental seed provisioning. Offspring from parents grown under drought showed no improved drought tolerance. Moreover, no PE were detectable when offspring were grown without neighbours. Our results suggest a novel path of adaptive PE: higher competitive ability was induced in offspring that were more likely to experience high neighbour densities. Together with the lack of adaptive PE towards drought tolerance, this emphasizes that a correlation between parental and offspring environment is crucial for adaptive PE to evolve. Our results also call for the inclusion of competitive effects in future PE studies. Synthesis. This study demonstrates the important role of adaptive PE for plant fitness (regarding competition) but also their limits (regarding drought) in temporally variable environments, based on the predictability of the respective environmental factor.

Oxidative stress markers in hypertensive states of pregnancy: preterm and term disease.

Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.

OS087. Maternal characteristics, mean arterial pressure and PLGF in early prediction of preeclampsia

In a previous study, we described the predictive value of first-trimester pregnancy-associated plasma protein-A (PAPP-A), free beta-subunit of human chorionic gonadotrophin (fb-hCG), Placental Growth Factor (PlGF) and A Desintegrin And Metalloproteinase 12 (ADAM12) for early onset preeclampsia (delivery <34 weeks) [1]. The objective of the current study was to obtain the predictive value of these serum makers, for both early onset PE (EOPE) and late onset PE (LOPE), combined with maternal characteristics and first-trimester maternal mean arterial blood pressure (MAP). This was a nested case-control study, using stored first-trimester maternal serum from 167 women who subsequently developed PE, and 500 uncomplicated singleton pregnancies which resulted in a live birth =>37 weeks. Maternal characteristics (i.e. medical records, parity, weight, length) MAP and pregnancy outcome (i.e. gestational age at delivery, birthweight, fetal sex) were collected for each individual and used to calculate prior risks for PE in a multiple logistic regression model. MAP values and marker levels of PAPP-A, fb-hCG, PlGF and ADAM12 were expressed as multiples of the gestation-specific normal median (MoMs). Subsequently, MoMs were log-transformed and compared between PE and controls using Student's t-tests. Posterior risks were calculated using different combinations of variables;(1) maternal characteristics, serum markers, and MAP separately (2) maternal characteristics combined with serum markers or MAP (3) maternal characteristics combined with serum markers and MAP. The model-predicted detection rates (DR) for fixed 10% false-positive rates were obtained for EOPE and LOPE with or without intra-uterine growth restriction (IUGR,birth weight <10th centile). The maternal characteristics: maternal age, weight, length, smoking status and nulliparity were discriminative between PE and control groups and therefore incorporated in the multiple logistic regression model. MoM MAP was significantly elevated (1.10 p<0.001; 1.07 p<0.001) and MoM PlGF was significantly reduced (0.95 p=0.016; 0.90 p=0.029) in the EOPE and LOPE group, respectively. The differences in markers for IUGR groups were larger. The estimated DRs of the three different models are presented in the table. This study demonstrates that first-trimester MAP and PlGF combined with maternal characteristics are promising markers in risk assessment for PE. Combination of markers proved especially useful for risk assessment for term PE. Detection rates were higher in the presence of IUGR.

Mid-gestational maternal cardiac function as a marker for the subsequent development of preeclampsia

ObjectivesPreeclampsia (PE) is characterised by cardiac remodelling and biventricular diastolic dysfunction. Preterm but not term PE, is also associated with severe left ventricular hypertrophy and biventricular systolic dysfunction. It is...

O15. Non-invasive assessment of hemodynamics in early pregnancy

study is to assess cardiac function/remodelling at mid-gestation in normotensive women, some of whom subsequently developed PE. Methods: This was a prospective study on 351 women assessed at 20-23 weeks gestation. In particular, women at increased risk of developing PE (127 with high resistance uterine artery Doppler indices and 79 with PE in a previous pregnancy) were recruited. Women underwent blood pressure profiling, echocardiography, cardiac tissue Doppler and strain rate analysis. Results: PE subsequently developed in 53 women (22 preterm, 31 at term). Five (23%) of women who developed preterm PE exhibited evidence of global diastolic and/or systolic dysfunction as well as left ventricular remodelling at midgestation. These features were not evident in women who subsequently developed term PE or had a normal pregnancy outcome (p < 0.0001). Conclusions: This study demonstrates that impaired cardiac function and remodelling precede the onset of preterm PE by several weeks in a quarter of cases. The majority of women who develop preterm PE and all women who develop term PE have normal global cardiac function and geometry at mid-gestation. Women with mid-gestation abnormal cardiac findings may have preexisting myocardial dysfunction. These cardiac findings may be useful in screening for the onset of preterm PE and may persist in the postnatal period influencing the long-term cardiovascular outlook.