Objective: The aim of this study was to determine the factors predicting the probability of severe postpartum hemorrhage in women undergoing repeat cesarean delivery. Design: This multicenter, retrospective cohort study based on data from 11 public tertiary hospitals within 7 provinces of China. Setting: 11 public tertiary hospitals within 7 provinces of China. Population: 11074 eligible pregnant women who had a history of cesarean delivery and undergo cesarean delivery again after 28 weeks of gestation. Methods: The cohort was divided into the development and validation sets. The all-variables model and the multivariable logistic regression model (simple model) were fitted to estimate the probability of severe postpartum hemorrhage. Results: Six independent risk factors of severe postpartum hemorrhage in the simple model were selected from 40 clinical information features including a history of endometrial injury, complications with placenta previa or placenta accreta, lower gestational age at delivery, pelvic adhesion, and previous uterine incision status. Our final simple model showed excellent discrimination and calibration, with areas under the ROC curve of more than 0.90 in the validation set. Conclusions: Predictive tools based on patient clinical characteristics can be used to accurately estimate the probability of severe postpartum hemorrhage in patients undergoing repeat cesarean delivery. Funding National Key R&D Program of China (No. 2016YFC1000405 and 2017YFC1001402) and the National Natural Science Foundation (No. 81830045, 81671533 and 81571518). Keywords repeat cesarean deliveries; severe postpartum hemorrhage; placenta previa; placenta accrete; pelvic adhesion; prediction; obstetrics

The aim of this study was to design a decision-making questionnaire for selection of prenatal care provider and determine its psychometric properties. Design: The present study is a mixed-method exploratory research Setting: Three maternity hospitals in Shiraz, Iran. Population: In a sample of 300 low-risk pregnant women, we examined the factor structure, reliability, and validity of the CPCP. Methods In the qualitative phase, were selected 23 pregnant women as well as 10 midwives and gynecologists. The samples sat a semi-structured individual interview. In the next step, the questionnaire items were designed based on the results of the qualitative phase and a review literature. In the quantitative phase, face validity, content validity, construct validity, internal consistency and stability were used to investigate the psychometric properties of the CPCP-60 questionnaire. Results: developed questionnaire consisted of 74-item which were reduced to 60 items after the face and content validity was determined qualitatively and quantitatively. The Exploratory factor analysis results revealed the professional skills, communication skills, personal characteristics of prenatal care providers, and characteristics of pregnancy and childbirth centers which accounted for 60.52% of the total variance. Cronbach’s alpha coefficient (0.947) and test-retest (0.951) indicated excellent internal consistency and stability of the questionnaire. Conclusion: Since the designed questionnaire of CPCP-60 is a valid and reliable instrument commensurate with the cultural conditions of society, it can be used in research and clinical settings to assess the pregnant women’s decision making for selection of prenatal care providers in Iran.

Mini-commentary on BJOG-19-1824.R1: Demographics, Natural History and Treatment Outcomes of Non-Molar Gestational Choriocarcinoma; A UK population study

Maintaining immune tolerance is a dynamic biological process which is provided by various types of tolerance mechanisms. In the light of the remarkable role of co-inhibitory receptors for switching-off the immune system, the potential impact of these receptors in controlling auto-reactivity is needed to be interrogated. Recent investigations suggested that the dysregulation of co-inhibitory receptors in chronic immune responses including cancer and chronic infections can result in immunological consequences called exhaustion. Exhaustion confer a potent “switch-off” mechanism for immune response. Using both co-inhibitory receptors and transcription factors in controlling T cells behavior, this review provide an overview of the potential effects of co-inhibitory receptors in maintaining tolerance and discuss how impaired co-inhibitory receptors might results in autoimmunity.

Marsupialization and fistulization are current surgical procedures for the treatment of symptomatic Bartholin duct cysts and gland abscesses. Other combined application methods include silver nitrate, carbon dioxide (CO2) lasers, aspiration and alcohol sclerotherapy. However, except for Word catheterization, most of these methods are relatively time-consuming and are not associated with low recurrence rates. Here, we describe a minimally invasive surgical technique that involves the application of radiofrequency ablation (RFA) combined with a needle-like knife electrode to fistulize cysts or abscesses approaching treatment.

Title:Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC).Running title:Ondansetron in pregnancyPer DamkierMD, PhDDepartment of Clinical Biochemistry & Pharmacology Odense University Hospital, DenmarkDepartment of Clinical research University of Southern Denmark, DenmarkMail:pdamkier@health.sdu.dkPhone: +45 65 50 37 90Ondansetron is an effective antiemetic that is being widely used as a second-line treatment option for severe Nausea and Vomiting of Pregnancy (NVP) in accordance with clinical guidelines (1–4).In July 2019, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) released updated comprehensive assessment report on the use of ondansetron in first trimester (5). This report is a detailed assessment of the available published data on the subject, including responses to supplementary questions posed to the Marking Authorization Holder (MAH), and the authors to the two central publications discussed below. The ensuing Summary of product Characteristics (SmPC) was updated in November 2019 with important changes to section 4.6 “Fertility, pregnancy and lactation” (6), which now state that ondansetron should not be used in first trimester of pregnancy.We acknowledge that the EMA SmPC in principal only frames the way that the MAH are legally allowed to market their product within the EU. It does not bind the physician as such; they must act and adhere with reference to the legal framework of their respective countries. We also acknowledge that EMA operates within a given formalized set of options on SmPC phrasings. In everyday practice however, the wording of the SmPC has consequences for treatment options and decision support beyond those formal to the legal ramifications of the SmPC.We applaud the EMA for the following nuanced phrasings in the SmPC:Based on human experience from epidemiological studies, ondansetron is suspected to cause orofacial malformations when administered during the first trimester of pregnancy.In one cohort study including 1.8 million pregnancies, first trimester ondansetron use was associated with an increased risk of oral clefts (3 additional cases per 10 000 women treated; adjusted relative risk, 1.24, (95% CI 1.03-1.48)).The available epidemiological studies on cardiac malformations show conflicting results. We believe that data from animal studies are of less relevance in these and analogue situations with an abundance of human data available:“Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.”We do not believe that the most important sentence therein is appropriately substantiated or justified:“Ondansetron should not be used during the first trimester of pregnancy.”The latter statement comes with very clear and immediate consequences to clinical practice and pregnant women suffering from NVP. Previous somewhat contradictory data notwithstanding (7), the core of the discussion is down to the interpretation of two extraordinarily large sets of data. These are recent publications each comprising 80.000+ first-trimester exposed liveborn children. Previous studies with somewhat contradictory results comprise cumulated first trimester exposures less than 10% of these new data.Huybrechts et al., a well-established research group within studies of adverse pregnancy outcome following drug exposure during pregnancy with an elite publication track-record, published their large study in December 2018 (8). In this meticulously designed, conducted and reported study comprising 88.000 liveborn children exposed to ondansetron in first trimester, they reported no increased overall risk of malformations and null associations for any or cardiac malformations and a small increased risk for oral cleft. Compared to 1,727.000 unexposed liveborn, propensity score adjusted relative risks were 1.01 (95% CI 0.98-1.05), 0.99 (95% CI 0.93-1.06) and 1.24 (95% CI 1.03-1.48) for any, cardiac and oral cleft malformations, respectively. The increased risk of oral clefts corresponds to about 3 additional cases for every 10.000-liveborn children exposed to ondansetron in first trimester.Zambelli-Weiner et al. published their findings from a large study in January 2019 (9). This triggered controversy and extensive discussions among clinicians and researchers within the field.They reported data on 82.000 liveborn children exposed to ondansetron in first trimester. Compared to about 780.000 unexposed liveborn, their overall analysis identified a weak but no clinically meaningful association with cardiac effects, aOR 1.04 (95% CI 1.00-1.08) and a weak association to orofacial clefts, aOR 1.12 (95% CI: 0.95-1.33). Ade facto subgroup analysis – defined by the authors as “primary analysis” - restricted exposure to 5.500 women who were administered ondansetron in hospitals (“medical administration”). The inferential analysis substantially reinforced the overall weak signal for cardiac effects (aOR 1.43; 95% CI 1.28-1.61) but not orofacial clefts, (aOR 1.30; 95% CI: 0.75-2.25). The technical analysis appears suboptimal as adjustments were made as by a crude approach; i.e. the selection of confounder variables was based on these resulting in at least 10% change in effect estimates rather than simply including all selected confounders in the model.It appears plausible that this subpopulation of pregnant women in whom hospital treatment was deemed necessary, suffered from a more severe presentation of NVP, a confounder that they did not accounted for. The sensitivity analysis performed in patients assigned a diagnosis of NVP or hyperemesis gravidarum does not satisfactorily account for this. In almost all exposed cases, the exposure comprised a single intravenous dose of ondansetron. It is biologically counterintuitive that a causal relation to cardiac malformations be present based on such exposure. The paper reports extraordinarily high rates of congenital cardiac malformations be it among unexposed (3.7%) or exposed (5.5 and 4.1% for intravenous and any exposure, respectively) liveborn children. These observations are incompatible with all other reported data on the rate of congenital cardiac malformations. The external validity of the study findings is therefore less convincing and compromises comparisons to other findings.The authors did not provide satisfactory responses to additional questions poses by PRAC during the assessment process. Five specific questions were posed, and the authors did not address any of these. They provided a short narrative statement that did not serve to clarify or advance understanding of their findings (5). Not least, this paper is severely compromised by an initially undisclosed serious conflict of interest. The formal COI disclosure in the paper state: ”As an organization, TTi reports receiving funds from plaintiff law firms involved in ondansetron litigation…” The extent of this COI was only revealed during a litigation process. The specific study received substantial funding ($ 210.000) from plaintiffs’ representation who was pursuing litigative damage by claiming malformations from ondansetron use in pregnancy (10). It is the position of the undersigned and ENTIS Scientific Committee that this study is methodologically and ethically compromised to an extent that the results thereof cannot be considered when assessing the totality of evidence on the safety of ondansetron in pregnancy.Since the PRAC recommendation two additional studies have been published that should be considered in the overall assessment of the risk during pregnancy.In January 2020, Huybrechts et al. published an additional study on intravenous administration of ondansetron in early pregnancy and risk of congenital malformations (11). In this study, the authors revisited the study population from their original paper, but restricted their analysis to those women who received intravenous ondansetron in first trimester (8). The resulting propensity-score adjusted inferential analysis of about 24.000 pregnancies exposed to intravenous ondansetron did not result in increased risk of cardiac malformations (RR 0.97; 95% CI 0.86-1.10), oral clefts (RR 0.95; 95% CI 0.63-1.43), or any congenital malformation(RR 1.02; 95% CI 0.96-1.08). Unadjusted analyses suggested a small increased risk for cardiac and any malformation (11). These data strongly mitigate the previous data on intravenous ondansetron (9).Lemon and colleagues reported a small increased risk of ventricular septal defect (VSD) following first trimester exposure to intravenous or oral ondansetron in first trimester among 3700 pregnancies (12). Across various methodological approaches the adjusted risk ratio varied between 1.7 and 2.1 with 95% CI ranging between 1.0 and 4.0. In an overall analysis though there was no increased risk for any birth defect or any heart defect, illustrating the dilemma of splitting versus lumping in such analyses (13). In this study, there may be an issue of ascertainment bias. Women exposed to ondansetron likely suffered from more severe NVP and thus may have been be subject to more attention and their newborn babies to a greater extent are subject to an echocardiograph evaluation. VSDs may be clinically asymptomatic and ”Up to 80% of small, muscular VSDs and 30%-50% of perimembranous defects will close spontaneously” (14).In summary, we believe that the abundance of most methodologically convincing data on cardiovascular malformations is reasonably reassuring. Even if a small excess risk may still be present, ondansetron in first trimester should remain an option for pregnant women with severe NVP.It is the opinion of ENTIS that the EMA decision to explicitly discourage first trimester treatment with ondansetron puts pregnant women with severe NVP, physicians and health care professionals between a rock and a hard place. We do not agree that the specific wording against the use of ondansetron in first trimester is justified and we do not support the conclusion of EMA/PRAC assessment report and this section of the SmPC.We urge the EMA/PRAC to carefully consider everyday clinical consequences of formal regulatory decisions. In cases with likely widespread clinical consequences, we suggest that EMA/PRAC consult liberally with relevant patient organizations, clinicians and health care professionals before final adoption of a recommendation.

Background: Postpartum haemorrhage (PPH) rates are increasing in developed countries. A reliable prognostic tool for PPH has potential to aid prevention efforts. Objective: To systematically identify and appraise prognostic modelling studies for prediction of PPH. Search strategy: MEDLINE, Embase, CINAHL and the Cochrane Library were searched using a combination of terms and synonyms including ‘prediction tool’, ‘risk score’ and ‘postpartum haemorrhage’. Selection criteria: Any observational or experimental study developing a prognostic model for women’s risk of PPH. English language publications. Data collection and analysis: Predesigned data extraction form to record: data source; participant criteria; outcome; candidate predictors; actual predictors; sample size; missing data; model development; model performance; model evaluation; interpretation. Main Results: Of 1723 citations screened, 10 studies were eligible for inclusion. An additional paper was published and identified following completion of the search. Studies addressed populations of women who experienced; placenta praevia; vaginal births; caesarean birth; and the general obstetric population. Primary study authors deemed four models to be confirmatory. There was a high risk of bias across all studies due to a combination of retrospective selection of women, low sample size, no internal validation, suboptimal external validation and no reporting of missing data. Conclusion: Of eleven prognostic models for PPH risk, one developed for women undergoing caesarean section is deemed suitable for external validation. Future research requires robust internal and external validation of existing tools and development of a model that can be used to predict PPH in the general obstetric population. Protocol registration number: PROSPERO 95587

Misunderstanding of the function of the plateau pika (Ochotona curzoniae) results in diminishing the diversity of both fauna and flora species and collapse of the the food on the Qinghai-Tibetan plateau. We used data obtained during an 11-year period to observe evolutionary habitat selection by the plateau pika in relation to an irrelevant phylogeny agent of livestock management. We hypothesized that local nomads are the irrelevant phylogeny agent in the Kobresia ecosystem of the Qinghai-Tibetan plateau. In order to verify the above hypothesis, distance to nearest yak-bedding areas and dung management are the variables that most strongly explains variation in pika occupancy probability and probability of occupancy detection based on free-ranging livestock. Both occupancy and detection probability of pikas decrease sharply with increasing distance to nearest yak-bedding area, strongly suggesting that pika population densities are highest closest to yak-bedding areas. There is a strong correlation between dung cover and occupancy of the plateau pika—namely, the more dung drying on the ground; the more plateau pikas occupy the area. After the dung has damaged the grass, plateau pikas are apparently detected there. Thus, rangeland dominated by sedges of the genus Kobresia on the Qinghai-Tibetan Plateau is modified by livestock grazing and management, especially dung management. This is the first reported evidence that local nomads may cause expansion of the habitat of the plateau pika and its occupancy.

Anthropogenic perturbations such as harvesting often select against a large body size, and are predicted to induce rapid evolution towards smaller body sizes and earlier maturation. However, the evolvability of body size and size-correlated traits remains seldom evaluated in wild populations. Here, we use a laboratory experiment over 6 generations to measure the ability of wild-caught medaka fish (Oryzias latipes) to evolve in response to bidirectional size-dependent selection mimicking opposite harvest regimes. Specifically, we imposed selection against a small body size (Large line), against a large body size (Small line) or random selection (Control line), and measured correlated responses across multiple phenotypic, life-history and endocrine traits. As expected, the Large line evolved faster somatic growth and delayed maturation, but also evolved smaller body sizes at hatch, with no change in average levels of pituitary gene expressions of luteinizing, follicle-stimulating or growth (GH) hormones. In contrast, the Small medaka line was unable to evolve smaller body sizes or earlier maturation, but showed marginally-significant signs of increased reproductive investment, including larger egg sizes and elevated pituitary GH production. Natural selection on medaka body size was too weak to significantly hinder the effect of artificial selection, indicating that the asymmetric body-size response to size-dependent selection reflected an asymmetry in body-size evolvability. Our results show that trait evolvability may be contingent upon the direction of selection, and that a detailed knowledge of trait evolutionary potential is needed to forecast population response to anthropogenic change.

Gene annotation is a critical bottleneck in genomic research, especially for the comprehensive study of very large gene families in the genomes of non-model organisms. Despite the recent progress in automatic methods, state-of-the-art tools used for this task often produce inaccurate annotations, such as fused, chimeric, partial or even completely absent gene models for many family copies, errors that require considerable extra efforts to be corrected. Here we present BITACORA, a bioinformatics solution that integrates popular sequence similarity-based search tools and Perl scripts to facilitate both the curation of these inaccurate annotations and the identification of previously undetected gene family copies directly in genomic DNA sequences. We tested the performance of BITACORA in annotating the members of two chemosensory gene families with different repertoire size in seven available genome sequences, and compared its performance with that of Augustus-PPX, a tool also designed to improve automatic annotations using a sequence similarity-based approach. Despite the relatively high fragmentation of some of these drafts, BITACORA was able to improve the annotation of many members of these families and detected thousands of new chemoreceptors encoded in genome sequences. The program creates general feature format (GFF) files, with both curated and newly identified gene models, and FASTA files with the predicted proteins. These outputs can be easily integrated in genomic annotation editors, greatly facilitating subsequent manual annotation and downstream evolutionary analyses.

Quantitative evaluation of soil conservation effects (SCE) of ecological policies at the macro level is not only a summary of past ecological recovery experience but also an effective way to explore the optimization of future ecological policies. As a famous ecological policy, “Grain for Green” (GFG) carried out in the Loess Plateau of China has significantly reduced soil erosion in this region. However, it is unclear whether the implementation of this policy has achieved the optimal SCE, which is an important issue in the GFG evaluation. The concept of soil conservation potential (SCP) was proposed in this study. Taking Yan’an, China as an example, the influence of GFG on soil erosion control was evaluated by comparing the total amount of soil erosion reduction and the SCP under certain the GFG intensity. On this basis, the future measures of GFG optimization were proposed. The result shows that the implementation of GFG in the past does not take into account the local SCP, and there is a significant spatial mismatch between the GFG implementation intensity and the SCP, resulting in the waste of resources and low policy efficiency. If this problem was fully considered in ecological restoration planning, a “win-win” result of improving governance effect and reducing input cost could be achieved. Finally, the suggestion of establishing the GFG dynamic input mechanism was put forward for the formulation and optimization of relevant ecological policies in the future.

1. Plant leaf stomata are the gatekeepers of the atmosphere-plant interface and are essential building blocks of land surface models as they control transpiration and photosynthesis. Although more stomatal trait data is needed to significantly reduce the error in these model predictions, recording these traits is time-consuming and no standardized protocol is currently available. Some attempts were made to automate stomatal detection from photomicrographs, however, these approaches have the disadvantage of using classic image processing or targeting a narrow taxonomic entity which makes these technologies less robust and generalizable to other plant species. We propose an easy-to-use and adaptable workflow from leaf to label. A methodology for automatic stomata detection was developed using deep neural networks according to the state-of-the-art and its applicability demonstrated across the phylogeny of the angiosperms. 2. We used a patch-based approach for training/tuning three different deep learning architectures. For training, we used 431 micrographs taken from leaf prints made according the nail polish method from herbarium specimens of 19 species. The best performing architecture was tested on 595 images of 16 additional species spread across the angiosperm phylogeny. 3. The nail polish method was successfully applied in 78% of the species sampled here. The VGG19 architecture slightly outperformed the basic shallow and deep architectures, with a confidence threshold equal to 0.7 resulting in an optimal trade-off between precision and recall. Applying this threshold the VGG19 architecture obtained an average F-score of 0.87, 0.89 and 0.67 on the training, validation and unseen test set, respectively. The average accuracy was very high (94%) for computed stomatal counts on unseen images of species used for training. 4. The leaf-to-label pipeline is an easy-to-use workflow for researchers of different areas of expertise interested in detecting stomata more efficiently. The described methodology was based on multiple species and well-established methods so that it can serve as a reference for future work.

Diatoms are a globally successful and eukaryotic photosynthetic group with an ornamented silica external wall. The relationship between their thecal diversity and habitat means that diatoms can be used as bioindicators to characterize the aquatic environment. To estimate the distribution and diversity of diatom communities during winter in South Korean coastal waters, we collected phytoplankton samples from 114 coastal sites. We applied the unweighted pair-group technique using the arithmetic averages clustering method to cluster the sampling sites—apart from those where the biota consisted of other groups, such as dinoflagellates—into four ecoregions: Yellow Sea (YS), Southern Sea (SS), Southern East Sea (SES), and Northern East Sea (NES). Indicator species analysis in each ecoregion led to the selection of tychoplanktonic, chain-forming, stalk-forming, and psychrophilic indicator diatoms, each of which represented a planktonic lifestyle associated with one of the four ecoregions. This study shows the diatom community to serve as bioindicators of Korean coastal water ecoregions, and the subsequent seasonal survey will provide a starting point for the improved understanding of Korean diatom-based ecoregions, in both time and space.

1. Gummosis on Acacia decurrens, an invasive tree species, that got established in Merapi Volcano National Park (MVNP) after the eruption of Mount Merapi in 2010 was studied to i) identify the causal organism of the disease, ii) analyze disease symptoms, iii) understand the spatio-temporal distribution of gummosis in the tree population and iv) examine how the disease affects the anatomy of tree wood. 2. Pathological, morphological and molecular studies were used in this studies. 3. Ceratocystis fimbriata was proved to be the causal organism of the disease. The disease spread was probably aided by the ambrosia beetle (Euwallacea sp.) which bores holes on the stem. 4. The disease is noted to spread from the base of the trees, where the ambrosia beetle bores holes first, to the upper part. 5. The number of parenchyma cells in the infected stem was significantly more than in the healthy stem which apparently facilitated water and nutrition transport within the tree helping it to grow normally despite serious gummosis. 6. The management of invasion by A. decurrens in the MVNP area poses a serious challenge due its success as an invader in the volcano impacted area and the threat of the gummosis pathogen spreading to other species both of which will affect the regeneration and establishment of native species and recuperation of the ecosystem.

Obtaining the hydraulic conductivity characteristics of widely distributed fault zones is the key to evaluating potential underground nuclear waste repositories. However, there are currently certain limitations on the methods for such data collection. In this study, electrical resistivity tomography (ERT) was combined with pumping test data to obtain the distribution of hydraulic conductivity in fault zones. The hydraulic conductivity of the aquifer was obtained through 30 pumping tests in seven pumping wells, and the results were then fitted with the aquifer resistivity obtained by the ERT at the corresponding positions to establish the relationship between the resistivity and the hydraulic conductivity, according to which the hydraulic conductivity characteristics of the fault zone can be obtained using the resistivity value. The results show that for the sandstone area with a small hydraulic conductivity, the result of exponential fitting is more accurate (R2 = 0.97) than that of linear fitting and power fitting. The hydraulic conductivity calculated based on the established R-K relationship has an error of less than 10.50% compared with that measured by the pumping tests, and the Nash-Sutcliffe efficiency coefficient is 0.96. Furthermore, the spatial distribution of the hydraulic conductivity of the fault zone in the study area was calculated based on this relationship, providing a basis for more accurate and low-cost descriptions of groundwater and solutions transport in the fault zone.

Water temperature is an important habitat factor in river ecosystems that exhibits the characteristics of continuous change. Dam construction disrupts the continuity of the water temperature and reset it, thus exerting range reduction and hysteresis effects on the characteristics of water temperature change. The effect of a dam on river continuity is directly related to the dam size. To explain this relationship quantitatively, two rivers in China were selected: one river without reservoirs and one river with cascade reservoirs. Through the analysis of the longitudinal change of water temperature in free-flowing rivers, we found that water temperature changes continuously and uniformly in the longitudinal direction. Based on this, a temperature trend hypothesis in river was proposed, and the discontinuity of the water temperature in the reservoir section was evaluated. The result is as follows: (1) In mixed reservoirs, river water temperature remains as continuous as free-flowing rivers. However, the river water temperature has a large discontinuity in the stratified reservoir; (2) Selective withdrawal of stratified reservoirs in January could not remove the discontinuity caused by itself, but it worked in June.

Phosphorus (P) is an essential mineral nutrient for plants. Nevertheless, excessive P accumulation in leaf mesophyll cells causes necrotic symptoms in land plants; this phenomenon is termed P toxicity. However, the detailed mechanisms underlying P toxicity in plants have not yet been elucidated. This study aimed to investigate the molecular mechanism of P toxicity in rice. We found that under excessive inorganic P (Pi) application, Rubisco activation decreased and photosynthesis was inhibited, leading to lipid peroxidation. Although the defence systems against reactive oxygen species (ROS) accumulation were activated under excessive Pi application conditions, the Cu/Zn-type superoxide dismutase activities were inhibited. A metabolic analysis revealed that excessive Pi application led to an increase in the cytosolic sugar phosphate concentration and the activation of phytic acid synthesis. These conditions induced mRNA expression of genes that are activated under metal-deficient conditions, although metals did accumulate. These results suggest that P toxicity is triggered by the attenuation of both photosynthesis and metal availability within cells mediated by phytic acid accumulation. Here, we discuss the whole phenomenon of P toxicity, beginning from the accumulation of Pi within cells to death in land plants.

Quantifying hydrologic exchange fluxes (HEF) and subsurface water residence times (RT) are important for managing the water quality and ecosystem health in dynamic river corridor systems. Because of limited field accessibility, numerical models typically have been used to quantify HEFs and RTs. These models, however, usually are limited to local-scale bedforms and are based on the assumption that hydrostatic pressure drives surface and subsurface water exchanges. Previous laboratory-scale experiments and models have shown that hydrodynamic pressure variations on the riverbed induced by dynamic river flows can strongly impact HEFs and RTs. In this study, the impacts of hydrodynamic pressure on HEFs and RT for a 30 km section of the Columbia River in Washington State over a three-year period were quantitatively evaluated using a coupled transient three-dimensional (3D) multi-phase surface and subsurface water flow transport approach. Based on comparisons of the model simulations with a reference case that considered only hydrostatic pressure, we found that hydrodynamic pressure significantly enhances upwelling and downwelling HEFs by 2 and 1.7 times, respectively, in the investigated river section and also leads to a reduction of the most likely RT by one order of magnitude (i.e., from hundreds of days to tens of days).

Soil microbial diversity distribution patterns and their ecological linkage with aboveground plant diversity are essential for both theoretical and applied ecology. However, a number of studies have shown soil microbial distribution patterns along different environmental gradients are inconsistent and their ecological linkages with plant diversity haven’t been well clarified. In this study, the plant and soil microbial diversity was simultaneously surveyed in 30 natural broadleaved forest sites along a 2500 km latitudinal gradient (18°–40°N) in China. The soil bacterial and fungal diversity was detected using the Illumina sequencing technique. The results showed soil bacterial and fungal community structure differed significantly among different sites and their alpha -diversity significantly increased as latitudinal increased (P < 0.001), and the plant and soil microbial beta-diversity was significantly linkages (P < 0.001). Based on the partial Mantel test, boosted regression tree and structural equation model analysis, we found plant alpha-diversity had no positive correlation with soil microbial alpha-diversity, and soil pH and climate condition (including mean annual precipitation and mean annual temperature) were the most important factors affecting soil microbial community structure. However, soil microbial heterogeneity might significantly affect aboveground plant community structure. Our analysis indicated that the plant beta-diversity could predict soil microbial beta-diversity at regional forest system, and soil pH plays higher roles than plant diversity in affecting soil microbial community at regional scale. This study provides new insights into the soil microbial diversity distribution patterns and ecological linkage between plant diversity and soil microbial diversity in natural forest ecosystem at the regional scale.

Anthropogenic disturbances greatly alter community composition and diversity. However, it remains largely unknown which underlying processes - colonizations, local extinctions or abundance changes - drive compositional changes in response to disturbance, and whether these processes are constrained by environmental gradients. Here, we investigated the processes underlying temporal turnover of vascular plant communities in boreal forests in response to silvicultural practices along a soil fertility gradient. Our analyses were based on long-term data from 1985 to 2006 covering up to 1700 sites across Finland. While average richness remained static, we found that silvicultural practices induced greatest turnover in the most fertile habitats. In recently disturbed sites, colonizations and species losses altered dominance structure of the communities, while the undisturbed old forests were characterized by stable dominant species even when the majority of species shifted their identity. We conclude that disturbance history and fertility constrain temporal turnover in boreal forest communities.

Morphology is expected to represent species' ecological niches, based on microhabitat and ecological selection pressures dictating morphological adaptations for efficient performance. However, the presence of competitor species is predicted to cause niches to contract. Therefore, an increase in species richness is expected to lead to narrower niches, and reduced overlap and distances between niches of different species. We tested these predictions on the skink fauna of New Guinea, the world's largest tropical island. We show that, while some morphospace metrics change predictably with species richness, elevation is a stronger predictor of morphospace occupancy. As elevation increases niches become narrower and closer to each other, and overall morphospace occupancy decreases. Highland skinks are, on average, smaller, thinner, and with shorter limbs than lowland species. We hypothesize that harsh climates in highland habitats impose strong selection on skinks to occupy specific areas of morphospace that facilitate efficient thermoregulation in sub-optimal thermal conditions.

Objective: To assess the impact of implementation of GAP in a multi-ethnic population with high obesity and high deprivation. Design/Methods: Retrospective before (2012) and after (2017) study (pre-and post-GAP). Outcomes were compared between epochs with adjustment for New Zealand Deprivation Index, maternal body mass index, ethnicity, cigarette smoking and age. Setting: Counties Manukau tertiary maternity facility, Auckland, New Zealand Population: Singleton, non-anomalous pregnancies, booked with a hospital midwife by 20 weeks’ gestation, with birth after 24 weeks’ gestation. Main Outcome Measures: Antenatal detection of SGA babies (<10th customised centile), labour induction, caesarean section and composite adverse neonatal outcome (neonatal unit admission >48 hrs, 5-minute Apgar Score <7, any ventilation). Results: Antenatal detection of SGA increased after introduction of GAP from 22.9% to 57.9% (aOR=4.81, 95% CI 2.82, 8.18) with similar SGA rates across epochs (13.8% vs 12.9%; p=0.68). Induction of labour and caesarean birth increased between epochs, but this increase was similar in SGA and non-SGA. Amongst SGA, increased antenatal identification post-GAP appeared to be associated with lower composite adverse neonatal outcome (identified SGA: pre-GAP 32.4% vs post-GAP 17.5%, aOR=0.44, 95% CI 0.17, 1.15; non-identified SGA: pre-GAP 12.3% vs post-GAP 19.3%, aOR=1.81, 95% CI 0.73, 4.48; interaction p=0.03). Conclusions: GAP was associated with an almost 5-fold increased likelihood for SGA detection, without significant increase in maternal intervention and some evidence of a reduction in composite adverse neonatal outcome in identified SGA pregnancies. GAP is a safe, effective tool for SGA detection in an ethnically diverse population with high obesity levels.

Objective: Define the prevalence of OSA in a population of obese pregnant women. Secondary objectives were to assess its obstetric consequences and define its risk factors in this population. Design – Setting – Population – Methods: This single-center prospective study took place at the Lille University Hospital from 2010 to 2016 and included pregnant women with a body mass index (BMI) > 35 kg/m2. They underwent polysomnography (type 1 sleep testing) between 24 and 32 weeks of gestation to diagnose OSA. Clinical, obstetric, and fetal data were collected monthly and at delivery. We compared the groups with and without OSA and calculated its prevalence. Main outcome measures - Results: This study included 67 women with a mean BMI of 42.4 ± 6.2 kg/m2. Among them, 29 had OSA, for a prevalence of 43.3% (95% confidence interval, 31.4–55.2); it was mild or moderate in 25 women and severe in 4. Comparison of the two groups showed that women in the OSA group were older (31.9 ± 4.7 years vs 29.5 ± 4.8 years, P=.045), had chronic hypertension more frequently (37.9% vs 7.9%, P=.0027), and had a higher mean BMI (43.8 ± 6.2 kg/m2 vs 41.2 ± 6 kg/m2, P=.045). During pregnancy, they developed gestational diabetes more often (48.3% vs 23.7%, P=.04). No significant differences were observed for any of the other criteria studied. Conclusions: The prevalence of OSA was high in our study, and women with it developed gestational diabetes during pregnancy more often. No other obstetric complications were obser

Glutathione (GSH) plays a central role in the redox balance maintenance in mammalian cells. The study of industrial CHO cell lines have demonstrated a close link between GSH metabolism and clone productivity. However, a deep investigation is still required to understand this correlation and highlights new potential targets for cell engineering. In this study, we have modulated the GSH intracellular content of an industrial cell line under bioprocess conditions in order to further elucidate the role of the GSH synthesis pathway. Two strategies were used : the variation of cystine supply and the direct inhibition of the GSH synthesis using buthionine sulfoximine (BSO). Cysteine supply modulation have revealed a correlation between intracellular GSH and product titer over time. Analysis of metabolites uptake/secretion rates and proteome comparison between BSO-treated cells and non-treated cells has highlighted a slow down of the TCA cycle leading to a secretion of lactate and alanine in the extracellular environment. Moreover, an adaptation of the glutathione related proteome has been observed with a up-regulation of the regulatory subunit of glutamate cysteine ligase and a down-regulation of a specific glutathione transferase subgroup, the Mu family. Surprisingly, the main impact of BSO treatment was observed on a global down-regulation of the cholesterol synthesis pathways. As cholesterol is required for protein secretion, it can be the missing part of the jigsaw to finally elucidate the link between GSH synthesis and productivity.