A global reptile assessment highlights shared conservation needs of tetrapods.

Comprehensive assessments of species' extinction risks have documented the extinction crisis1 and underpinned strategies for reducing those risks2. Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction3. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods4-7. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs6. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened-confirming a previous extrapolation8 and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods-agriculture, logging, urban development and invasive species-although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles-including most species of crocodiles and turtles-require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.

PHARE: a bioinformatics pipeline for compositional profiling of multiclonal Plasmodium falciparum infections from long-read Nanopore sequencing data.

BACKGROUND: The emergence of drug-resistant clones of Plasmodium falciparum is a major public health concern, and the ability to detect and track the spread of these clones is crucial for effective malaria control and treatment. However, in endemic settings, malaria infected people often carry multiple P. falciparum clones simultaneously making it likely to miss drug-resistant clones using traditional molecular typing methods. OBJECTIVES: Our goal was to develop a bioinformatics pipeline for compositional profiling in multiclonal P. falciparum samples, sequenced using the Oxford Nanopore Technologies MinION platform. METHODS: We developed the 'Finding P. falciparum haplotypes with resistance mutations in polyclonal infections' (PHARE) pipeline using existing bioinformatics tools and custom scripts written in python. PHARE was validated on three control datasets containing P. falciparum DNA of four laboratory strains at varying mixing ratios. Additionally, the pipeline was tested on clinical samples from children admitted to a paediatric hospital in the Central African Republic. RESULTS: The PHARE pipeline achieved high recall and accuracy rates in all control datasets. The pipeline can be used on any gene and was tested with amplicons of the P. falciparum drug resistance marker genes pfdhps, pfdhfr and pfK13. CONCLUSIONS: The PHARE pipeline helps to provide a more complete picture of drug resistance in the circulating P. falciparum population and can help to guide treatment recommendations. PHARE is freely available under the GNU Lesser General Public License v.3.0 on GitHub: https://github.com/Fippu/PHARE.

Flipping the classroom in neurological bedside teaching: a prospective controlled study.

BACKGROUND: Bedside teaching is essential to foster core clinical competences in medical education, especially in Neurology. However, bedside skills are declining and new concepts to enhance the effectiveness of bedside teaching are needed, also in view of limited in-person teaching possibilities in the ongoing pandemic situation. If theoretical knowledge is taught prior to in-person sessions this might allow to better focus on practical application aspects during bedside teaching. We thus aimed to answer the question to what extent such an approach can enhance the effectiveness of neurological bedside teaching. METHODS: In this prospective controlled study, neurological bedside courses following a traditional and a flipped classroom (FC) approach were compared with regards to their effects on theoretical knowledge and practical skills of medical students. Evaluations were obtained from 161 students and their lecturers participating in a neurological bedside teaching course at a German university hospital between October 2020 and July 2021. Students were randomly assigned to course dates. However, the 74 students assigned to course dates from May to July 2021 completed a mandatory online preparation course prior to the bedside teaching. These students served as the interventional group (IG) and the remaining 87 students formed the control group (CG). Ratings of knowledge and skills provided by the students and their lecturers on numerical rating scales served as primary outcome measures. Moreover, the time needed to recapitulate theoretical contents during the in-person teaching session was assessed as a secondary outcome measure. Group comparisons were performed using t-statistics. RESULTS: Theoretical knowledge upon entering the course was rated significantly higher in the IG by the students (p < 0.001) and lecturers (p = 0.003). Lecturers also rated the practical skills of students in the IG significantly higher (p < 0.001). Furthermore, significantly less time was needed to recapitulate theoretical contents during the in-person session in the IG (p = 0.03). CONCLUSIONS: Using a FC approach enhances the effectiveness of in-person neurological bedside teaching. Thus, these concepts are particularly valuable in the ongoing pandemic situation. Moreover, they might allow to reuse e-learning contents developed during the pandemic and to develop future bedside teaching concepts.

Effectiveness of non-bedside teaching during the COVID-19 pandemic: a quasi-experimental study.

BACKGROUND: The COVID-19 pandemic poses a huge challenge for clinical teaching due to contact restrictions and social distancing. Medical teachers have to balance potential risks and benefits of bedside teaching, especially in course formats intended to foster practical clinical skills. In this context, we aimed to address the question, whether presence-based teaching formats without patient involvement are suitable to teach practical skills. METHODS: In this quasi-experimental study, presence-based teaching formats with and without patient contact were retrospectively compared regarding their effects on medical students' theoretical knowledge and practical skills, i.e. the performance and clinical interpretation of the neurological exam. To this end, evaluations from 102 students and their lecturers participating in a neurological bedside teaching course at a German university hospital between October 2020 and April 2021 were obtained. Students were initially randomly assigned to course dates. However, 53 students assigned to courses in November and December 2020, were not able to go bedside due to contact restrictions. These students formed the interventional group and the remaining 49 students the control group. The primary outcome measures were students' overall grading of the course (school grades, 1-6) as well as ratings of knowledge and skills provided by the students themselves and their lecturers on a numerical rating scale (0-10). Comparison between groups was performed using frequentist and Bayesian t-statistics. RESULTS: The teaching format without patient contact received a significantly poorer overall grade by the students (p = 0.018). However, improvements in the students' self-ratings of knowledge and skills did not differ between the two formats (all p > 0.05, BF10max = 0.42). Moreover, especially practical skills were even rated significantly better in the group without patient contact by the lecturers (p < 0.001). CONCLUSIONS: Teaching formats without patient contact are less well-received by the students. However, they are able to teach practical skills regarding the performance and clinical interpretation of examination techniques. Still, the evaluations obtained might not adequately capture the importance of bedside teaching in preparing future physicians for their practice. Perspectively, hybrid teaching approaches including flipped-classroom concepts hold considerable potential to enhance effectiveness of bedside teaching in the present pandemic situation and in the future.

Rapid Identification of SARS-CoV-2 Variants of Concern Using a Portable peakPCR Platform.

The need for tools that facilitate rapid detection and continuous monitoring of SARS-CoV-2 variants of concern (VOCs) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To address this demand, we aimed at developing and evaluating a robust and fast diagnostic approach for the identification of SARS-CoV-2 VOC-associated spike gene mutations. Our diagnostic assays detect the E484K and N501Y single-nucleotide polymorphisms (SNPs) as well as a spike gene deletion (HV69/70) and can be run on standard laboratory equipment or on the portable rapid diagnostic technology platform peakPCR. The assays achieved excellent diagnostic performance when tested with RNA extracted from culture-derived SARS-CoV-2 VOC lineages and clinical samples collected in Equatorial Guinea, Central-West Africa. Simplicity of usage and the relatively low cost are advantages that make our approach well suitable for decentralized and rapid testing, especially in resource-limited settings.

Role of tip apices in scanning force spectroscopy on alkali halides at room temperature-chemical nature of the tip apex and atomic-scale deformations.

We have revealed processes of the tip apex distortion in the measurements of non-contact scanning force microscopy. High-spatial-resolution two-dimensional force mapping on KCl(100) surfaces for a large number of tips, seven tips, enabled us to see the complex behavior of the tip apex distortion. The tips are from Si without additional coating, but are altered by the tip-sample interaction and show the behavior of different atomic species. On the KCl(001) surfaces, the tip apex, consisting of K and Cl atoms or of Si, distorted several times while changing the distance even in a weak attractive region. There are variations in rigidity of the tip apex, but all tips distorted in the small attractive region. This complex behavior was categorized in patterns by our analyses. We compare the experimental force-distance data to atomistic simulations using rigid KCl-terminated tips and KCl-terminated tips with an additional KCl-pair designed to perform atomic jumps. We also compare the experimental force-distance data to first principles simulations using Si tips. We mainly find K-terminated tips and Si-terminated tips. We find that Si tips show only one force minimum whereas KCl-terminated tips show two force minima in line with the stronger rigidity of Si compared to KCl. At room temperature, the tip apex atoms can perform atomic jumps that change the atomic configuration of the tip apex.

Retrospective analysis of secondary resection of the cervical stump after subtotal hysterectomy: why and when?

PURPOSE: The rates of hysterectomy are falling worldwide, and the surgical approach is undergoing a major change. To avoid abdominal hysterectomy, a minimally invasive approach has been implemented. Due to the increasing rates of subtotal hysterectomy, we are faced with the following questions: how often does the cervical stump have to be removed secondarily, and what are the indications? METHODS: This was a retrospective, single-centre analysis of secondary resection of the cervical stump conducted from 2004 to 2018. RESULTS: Secondary resection of the cervical stump was performed in 137 women. Seventy-four percent of the previous subtotal hysterectomy procedures were performed in our hospital, and 26% were performed in an external hospital. During the study period, 5209 subtotal hysterectomy procedures were performed at our hospital. The three main indications for secondary resection of the cervical stump were prolapse (31.4%), spotting (19.0%) and cervical dysplasia (18.2%). Unexpected histological findings (premalignant and malignant) after subtotal hysterectomy resulted in immediate (median time, 1 month) secondary resection of the cervical stump in 11 cases. In four patients, the indication was a secondary malignant gynaecological disease that occurred more than 5 years after subtotal hysterectomy. The median time between subtotal hysterectomy and secondary resection of the cervical stump was 40 months. Secondary resection of the cervical stump was performed vaginally in 75.2% of cases, laparoscopically in 20.4% of cases and abdominally in 4.4% of cases. The overall complication rate was 5%. CONCLUSION: Secondary resection of the cervical stump is a rare surgery with a low complication rate and can be performed via the vaginal or laparoscopic approach in most cases. The most common indications are prolapse, spotting and cervical dysplasia. If a secondary resection of the cervical stump is necessary due to symptoms, 66.6% will be performed within the first 6 years after subtotal hysterectomy.

Measurement of the uterocervical angle for the prediction of preterm birth in symptomatic women.

PURPOSE: To examine if the uterocervical angle (UCA) can be used to predict preterm delivery in women with painful and regular uterine contractions and a cervical length of 25 mm or less. METHODS: Retrospective study at the perinatal unit of the University Hospital of Tuebingen, Germany. Women with singleton gestation and preterm contractions between 24 + 0 and 33 + 6 weeks' gestation were included. For the UCA measurement, a line is placed from the internal os to the external os irrespective of whether the cervix is straight or curved. A second line is drawn to delineate the lower uterine segment. The angle between the two lines is the UCA measurement. The measurements were taken on stored images from our database. RESULTS: The study consisted of 213 singleton pregnancies. At the time of UCA measurement, median maternal and gestational age was 31.4 years and 29.7 weeks' gestation. Median gestational age at delivery was 35.3 weeks and the corresponding birth weight 2480 g, respectively. The UCA measurement in women who delivered within 2 days, between 3-7 days and after 7 days was not helpful to distinguish between these three groups [median UCA measurements: 108.5°, 108.0° and 107.3° (Kruskal-Wallis test p = 0.576)]. Uni- and multivariate logistic multiple regression analysis demonstrated that the delivery within 2 days was only dependent on the gestational age and the cervical length at the time of presentation. CONCLUSION: The measurement of UCA is not useful in predicting preterm birth in the subsequent 7 days after an episode of preterm contractions.

The immunopeptidomic landscape of ovarian carcinomas.

Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells. Most strikingly, ligands derived from mucin 16 and mesothelin, a molecular axis of prognostic importance in EOC, are prominent in a majority of patients. Differential gene-expression analysis has allowed us to confirm the relevance of these targets for EOC and further provided important insights into the relationship between gene transcript levels and HLA ligand presentation.

Fetal profile in fetuses with open spina bifida.

OBJECTIVE: To determine whether the frontomaxillary facial (FMF) angle and the prefrontal space ratio (PFSR) are helpful in screening for open spinal defects by ultrasound in the second and third trimesters of pregnancy. METHODS: The FMF angle and the PFSR were measured in fetuses with spina bifida according to standardized protocols. The normal range of the PFSR was previously published by our group. To determine the normal values for the FMF angle in the second and third trimesters of pregnancy, we used the same stored images from the above-mentioned study. RESULTS: 71 affected and 279 normal fetuses were included in this study. Median gestational ages in the two groups were 21.1 weeks and 21.6 weeks, respectively. In fetuses with spina bifida, the FMF angle was significantly smaller than in the normal population (72.9° versus 79.6°). However, the measurement was below the fifth centile in only 22.5% of the affected fetuses. The PFSR was similar in both groups. CONCLUSIONS: The FMF angle is smaller in second and third trimester fetuses with open spina bifida. However, the difference is not large enough to implement this marker in current screening programs.

First Trimester Screening for Common Trisomies and Microdeletion 22q11.2 Syndrome Using Cell-Free DNA: A Prospective Clinical Study.

OBJECTIVES: The aims of the study were to assess the false-positive and uninformative test rate with first trimester cell-free DNA (cfDNA) screening for common trisomies and microdeletion 22q11.2 (22q11.2DS) and to examine women's attitudes toward such an approach. METHODS: This is a prospective study at the Prenatal Medicine Department of the University of Tübingen, Germany, at 11-13 weeks. In all pregnancies, a detailed ultrasound examination was carried out, followed by a cfDNA analysis for common trisomies and 22q11.2DS. In cases where the cfDNA analysis indicated 22q11.2DS, invasive prenatal diagnostic testing and parental testing were performed. After delivery, a detailed neonatal clinical examination was carried out including further genetic testing. Prior to counselling about the study, we asked the pregnant women who were potentially eligible for the study to anonymously report on their knowledge about 22q11.2DS. RESULTS: A total of 1,127 pregnancies were included in the final analysis of the study. The first cfDNA test was uninformative in 15 (1.33%) pregnancies. In 10 (0.89%) cases, the test remained uninformative, even after the second blood sample. There were 3 (0.27%) cases with a positive cfDNA test for 22q11.2DS. In all, 983 women returned the anonymous questionnaire prior to study participation. Only 80 (8.1%) women responded that they felt familiar or very familiar with 22q11.2DS. CONCLUSION: The addition of 22q11.2DS in first trimester cfDNA screening for common trisomies is feasible. The uninformative test rate for common trisomies and 22q11.2DS is 0.9%, and the false-positive rate for 22q11.2DS is 0.3%. Awareness and education around 22q11.2DS should be improved.

First trimester uterine artery pulsatility index levels in euploid and aneuploid pregnancies.

OBJECTIVE: To examine whether the uterine artery PI is different in aneuploid and euploid pregnancies. METHODS: Retrospective case-matched study at the department of prenatal medicine at the University of Tuebingen, Germany. The study involved patients with complete data on first trimester screening for trisomies and preeclampsia except PlGF. For each case with trisomy 21 we randomly selected 50 cases with a euploid fetus where complete data on screening for aneuploidy and preeclampsia were also available. The uterine artery pulsatility index and the corresponding MoM values of euploid and the aneuploid population were compared with a Man-Whitney U test. RESULTS: The dataset consisted of 4591 singleton pregnancies. The karyotype was normal in 4500 cases and was abnormal in the remaining 91 pregnancies. There were 50 pregnancies with trisomy 21, 31 with trisomy 18 and 13, and 10 with triploidy. In the group with euploid fetuses, median uterine artery PI was 1.55 (0.99 MoM). In the group with trisomy 21, the median PI (1.42) and MoM (0.89) levels were both significantly lower than in the euploid (p < 0.001). However, the measurements in the trisomy 18 and 13 [1.61 (0.93 MoM)] and in the triploidy [1.99 (1.13 MoM)] groups were not significantly different from those in the euploid group (p = 0.468 and p = 0.632, respectively). CONCLUSION: In conclusion, uterine artery PI levels in the first trimester are slightly lower in pregnancies with trisomy 21. This knowledge may prove to be useful in cases where a low PAPP-A level is seen on the first trimester maternal serum biochemical evaluation to differentiate whether the more likely cause for this finding is placental dysfunction or aneuploidy, specifically trisomy 21.

Splenic artery blood flow as a potential marker for materno-fetal transmission of a primary CMV infection.

OBJECTIVE: To examine the blood flow in the splenic artery as marker for materno-fetal transmission at about 20 weeks following a maternal first-trimester primary CMV infection. METHODS: This is a retrospective study at the prenatal medicine unit at University of Tuebingen, Germany. Women were included who underwent an amniocentesis to examine the fetal infection status following a maternal primary CMV infection in the first trimester. In all cases, amniocentesis was done at about 20 weeks and at least 6 weeks after the maternal infection. As part of the detailed ultrasound examination prior to each amniocentesis, we examined the peak systolic velocity flow (PSV) and the pulsatility index (PI) of the splenic artery. Measurements were transformed into MoMs according to the normal curves of Ebbing et al. RESULTS: 81 Women fulfilled the inclusion criteria. Maternal and gestational age was 31.9 years and 20.6 weeks' gestation. Maternal-fetal transmission occurred in 13 of the cases. In fetuses without and with a CMV infection, mean PI was 0.98 MoM and 0.89 (p = 0.081). Mean PSV was significantly higher in the group of infected fetuses than in those without (1.24 vs. 0.94 MoM, p = 0.026). CONCLUSION: The PSV may be a marker for maternal-fetal CMV transmission following a first-trimester maternal infection.

False-positive rates in screening for trisomies 18 and 13: a comparison between first-trimester combined screening and a cfDNA-based approach.

PURPOSE: To determine the false-positive rates (FPR) associated with screening for trisomy 18/13 using first-trimester combined screening (FTCS) and an ultrasound plus cfDNA-based approach (US-cfDNA), which includes a detailed ultrasound examination, a cfDNA analysis and a FTCS reflex backup test for cases with uninformative results. METHODS: This is a sub-analysis of a randomized controlled trial, which was performed between 2015 and 2016. Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (NT < 3.5 mm, no anomalies) were randomized into two groups: FTCS and US-cfDNA screening. The overall FPR in screening for trisomies 18/13 and 21 was compared with the FPR in screening for trisomy 21 alone. Pregnancies were considered screen positive if the risk for trisomy 21 was 1:100 and for trisomy 18 and 13, 1:20 each. RESULTS: The study population consisted of 688 pregnancies in each study arm. In the FCTS group, median delta NT was 0.0 mm, free beta-hCG and PAPP-A 0.96 and 1.11 MoM. In the US-cfDNA group, median delta NT was 0.0 mm. In 10 pregnancies, the cfDNA analysis was uninformative. In the FTCS and in the US-cfDNA group, the FPR in screening for trisomy 21 was 2.5% and 0%. In both groups, the overall FPR was not increased by adding screening algorithms for trisomies 18 and 13. CONCLUSION: In conclusion, the addition of screening for trisomies 18 and 13 to screening for trisomy 21 does not significantly change FPR. This is true for both the FTCS and the US-cfDNA-based approach.

Dosing interval between mifepristone and misoprostol in second and third trimester termination.

OBJECTIVE: To compare several strategies for second trimester labor induction for termination of pregnancy (TOP) using misoprostol and mifepristone and to determine which one is more effective in accelerating the time to delivery. METHOD: This was a retrospective study in which pregnancies that underwent second and third trimester TOP due to fetal anomalies between 2007 and 2017 were classified into a group that received misoprostol alone, a group that received mifepristone followed by misoprostol on the same day, one where misoprostol was given 1 day after mifepristone and one where the medications were administered 2 days apart. The primary outcome measure was the induction to delivery interval. RESULTS: 481 pregnancies fulfilled the inclusion criteria. In 140 cases, mifepristone was not administered. 341 women received mifepristone prior to induction, which was administered on the day of induction in 85 cases, and 1 or 2 days prior to induction in 140 and 19 cases. Median time interval between first induction and delivery was 15.0 (IQR 10.0-24.1) h in case no mifepristone was given and 13.2 (9.7-18.2) h if mifepristone was given on the same day and 9.3 (6.6-14.9) and 10.5 (7.2-22.3) h, if mifepristone was given 1 or 2 days prior to induction. After 24 h, the proportion of terminated pregnancies in each of the four groups was 75.0, 83.5, 93.2 and 78.9%. CONCLUSION: A 1 day interval between mifepristone and misoprostol is more effective in second and third trimester TOP compared to other strategies in terms of reducing the induction to abortion interval.

Demographic changes and effects on the mode of delivery: a retrospective analysis of a large birth registry containing 27,729 singleton deliveries in a level I center.

PURPOSE: To characterize and understand the demographics (age and body mass index, BMI) of a cohort of women who delivered at a single institution over an 11-year period. The purpose of this analysis is to look for effects over time of demographic characteristics on mode of delivery. METHODS: Retrospective analysis of singleton deliveries between 2004-2014, n = 27,729; level 1 perinatal center, university hospital setting. Data were extracted from the digital birth registry. All statistical analyses were done using R version 3.5.1. Variables analyzed were: age, BMI, and mode of delivery (in the current and any prior pregnancies). RESULTS: Mean age increased from 31.1 ± 5.2 years in 2004 to 31.5 ± 5.0 years in 2014 (p < 0.001, eta2 = 0.0006). Mean BMI before pregnancy increased from 23.7 ± 4.5 to 24.7 ± 5.2 kg/m2. Mean BMI at delivery increased from 28.5 ± 4.7 to 29.6 ± 5.2 kg/m2 (p < 0.001, eta2 = 0.0049). Regarding maternal age, patients with elective Cesarean section (CS) (32.5 ± 5.3 years), emergency CS (31.6 ± 5.6 years) and CS in labor (31.4 ± 5.3 years) were older compared to those with spontaneous (31.0 ± 5.2 years) or instrument-assisted vaginal delivery such as vacuum (31.0 ± 5.0 years) and forceps (30.2 ± 5.4 years). Among the multiparous patients, the mode of delivery in prior pregnancies is the variable with the greatest effect on the mode of delivery in any subsequent pregnancies. The mode of delivery was: spontaneous (55.5%), vaginal operative including vacuum and forceps (8.8%), and Cesarean section (35.7%). CONCLUSIONS: Increase of age and BMI over years is significant, but very small and in a range which seems not clinically relevant. Previous births have the strongest effects on mode of delivery in the current pregnancy.

The preferred mode of delivery of medical professionals and non-medical professional mothers-to-be and the impact of additional information on their decision: an online questionnaire cohort study.

PURPOSE: It was the aim to evaluate the personal preference of mode of delivery and to analyze differences between medical professionals and non-medical professionals. Interest in participating in a risk stratification system was evaluated. We hypothesized that gaining information about risk stratification provided in the survey could potentially change participants' decision regarding the preferred mode of delivery; therefore, subjects were asked twice (before and after providing information). METHODS: Five cohorts [four professionals (MP) including participants of the German Urogynecology Congress 2017, employees of two major university hospitals in Germany, and members of the German Society of Gynecology and Obstetrics, and one non-professional group (NP) including pregnant women] were invited online to participate in this survey. RESULTS: Vaginal delivery was the preferred mode of delivery in both groups (MP 90.4% vs. NP 88.8%; p = 0.429). MP are more likely to opt for CS due to concerns regarding pelvic floor disorders (MP 56.6% vs. NP 9.1%; p < 0.001). Likewise, parity and prior experienced CS (pCS) had a significant impact on the decision towards vaginal delivery (parity MP OR 7.5 95% CI 4.6-12.3, NP OR 9.3 95% CI 1.9-44.2; (pCS) MP OR 0.12 95% CI 0.07-0.19, NP OR 0.05 95% CI 0.01-0.25). There is great interest in participating in risk stratification systems in the majority of participants (68.9%). CONCLUSIONS: MP and NP prefer vaginal birth for themselves or their partners. Within the group that opted for CS, MP were significantly more often concerned about pelvic floor disorders. Future prevention aspects might include education about pelvic floor disorders.

False-Positive Rate in First-Trimester Screening Based on Ultrasound and Cell-Free DNA versus First-Trimester Combined Screening with Additional Ultrasound Markers.

OBJECTIVE: To determine whether screening for trisomy 21 based on first-trimester combined screening (FTCS) with assessment of nasal bone (NB), tricuspid flow (TCF), and ductus venosus flow (DVF) results in similar false-positive rates compared to ultrasound and cell-free DNA (cfDNA) screening. METHODS: This is a subanalysis of a prospective randomized controlled trial which was performed between October 2015 and December 2016. Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks' gestation were randomized into two groups: (1) FTCS with assessment of the NB, TCF, and DVF (extended FTCS [eFTCS]), and (2) ultrasound + cfDNA screening. The false-positive rate in screening for trisomy 21 was defined as the primary outcome parameter. RESULTS: The study population consisted of 688 women in each study arm. In the eFTCS group, the median delta fetal nuchal translucency thickness (NT) was 0.0 mm, free beta-hCG and PAPP-A were 0.96 and 1.11 MoM, and NB, TCF, and DVF PIV were abnormal in 0.9, 0.6, and 7.0% cases. In the ultrasound + cfDNA group, the median delta NT was 0.0 mm. In 10 pregnancies the cfDNA analysis was uninformative and the risk of trisomy 21 was based on eFTCS. There were no false-positive cases in the ultrasound + cfDNA group, whereas the false-positive rates were between 0.9 and 2.2% with eFTCS. CONCLUSION: Screening for trisomy 21 based on ultrasound + cfDNA has a lower false-positive rate than screening based on eFTCS.

First trimester screening for major cardiac defects based on the ductus venosus flow in fetuses with trisomy 21.

OBJECTIVE: To examine whether in fetuses with trisomy 21 (T21), the ductus venosus (DV) flow differs in presence of a major cardiac defect (congenital cardiac defect [CHD]) and whether this affects the risk distribution in first trimester screening for T21. METHODS: This retrospective study included pregnant women who underwent first trimester screening. This involves an examination of the crown-rump length, the nuchal translucency, the ductus venosus (DV) flow, and the heart. Three groups of fetuses were examined: euploid without CHD, T21 with CHD, and T21 without CHD. We examined the DV pulsatility index for veins, the direction of the a-wave, and ratios of velocities: v/S, v/D, a/S, a/D, and S/D. RESULTS: The study population consisted of 410 euploid fetuses and 136 with T21 (51 with CHD and 85 without CHD). In the 3 groups, the a-wave was reversed in 3.2%, 66.7%, and 57.6%. The DV flow ratios in T21 with and without CDH were significantly different compared with normal fetuses. When comparing the ratios between the 2 T21 groups, only the a/S and a/D ratio were significantly different. The risk distributions in screening for T21 with and without CDH were similar. CONCLUSION: There are some small differences in the DV flow of T21 fetuses with and without CHD, but they are not clinically useful.

Quantification of oxygen metabolic rates in Human brain with dynamic 17 O MRI: Profile likelihood analysis.

PURPOSE: Parameter identifiability and confidence intervals were determined using a profile likelihood (PL) analysis method in a quantification model of the cerebral metabolic rate of oxygen consumption (CMRO2 ) with direct 17 O MRI. METHODS: Three-dimensional dynamic 17 O MRI datasets of the human brain were acquired after inhalation of 17 O2 gas with the help of a rebreathing system, and CMRO2 was quantified with a pharmacokinetic model. To analyze the influence of the different model parameters on the identifiability of CMRO2 , PLs were calculated for different settings of the model parameters. In particular, the 17 O enrichment fraction of the inhaled 17 O2 gas, α, was investigated assuming a constant and a linearly varying model. Identifiability was analyzed for white and gray matter, and the dependency on different priors was studied. RESULTS: Prior knowledge about only one α-related parameter was sufficient to resolve the CMRO2 nonidentifiability, and CMRO2 rates (0.72-0.99 µmol/gtissue /min in white matter, 1.02-1.78 µmol/gtissue /min in gray matter) are in a good agreement with the results of 15 O positron emission tomography studies. Nonconstant α values significantly improved model fitting. CONCLUSION: The profile likelihood analysis shows that CMRO2 can be measured reliably in 17 O gas MRI experiment if the 17 O enrichment fraction is used as prior information for the model calculations. Magn Reson Med 78:1157-1167, 2017. © 2016 International Society for Magnetic Resonance in Medicine.