Precursor-free eruption triggered by edifice rupture at Nyiragongo volcano.

Classical mechanisms of volcanic eruptions mostly involve pressure buildup and magma ascent towards the surface1. Such processes produce geophysical and geochemical signals that may be detected and interpreted as eruption precursors1-3. On 22 May 2021, Mount Nyiragongo (Democratic Republic of the Congo), an open-vent volcano with a persistent lava lake perched within its summit crater, shook up this interpretation by producing an approximately six-hour-long flank eruption without apparent precursors, followed-rather than preceded-by lateral magma motion into the crust. Here we show that this reversed sequence was most likely initiated by a rupture of the edifice, producing deadly lava flows and triggering a voluminous 25-km-long dyke intrusion. The dyke propagated southwards at very shallow depth (less than 500 m) underneath the cities of Goma (Democratic Republic of the Congo) and Gisenyi (Rwanda), as well as Lake Kivu. This volcanic crisis raises new questions about the mechanisms controlling such eruptions and the possibility of facing substantially more hazardous events, such as effusions within densely urbanized areas, phreato-magmatism or a limnic eruption from the gas-rich Lake Kivu. It also more generally highlights the challenges faced with open-vent volcanoes for monitoring, early detection and risk management when a significant volume of magma is stored close to the surface.

Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

Scanning near-field optical microscopy measurements and simulations of regularly arranged silver nanoparticles.

Silver nanoparticles on a glass substrate are experimentally investigated by aperture scanning near-field optical microscopy (a-SNOM). To understand the experimental results, finite-element-method simulations are performed building a theoretical model of the a-SNOM geometry. We systematically vary parameters like aperture size, aluminum-coating thickness, tip cone angle, and tip-surface distance and discuss their influence on the near-field enhancement. All these investigations are performed comparatively for constant-height and constant-gap scanning modes. In the end, we establish a reliable and stable optical model for simulating a-SNOM measurements, which is capable of reproducing trends observed in experimental data.

Litigations in orthopedics and trauma surgery: reasons, dynamics, and profiles.

BACKGROUND: In recent literature, the increasing number of medical litigations, both in terms of the number of cases being filed and the substantive costs associated with lawsuits, has been described. This study aims to provide an overview of the profile of litigation for orthopedic and trauma surgery to describe the differences and the development of the number of cases over time. PATIENTS AND MATERIALS: A retrospective review of all litigations between 2000 and 2017 was conducted using the institutional legal database. The causes of litigation were documented and classified into seven major categories. In addition to plaintiff characteristics, the litigation outcomes and the differences between emergency and elective surgery were analyzed. RESULTS: A total of 230 cases were evaluated. The mean age of the plaintiffs was 44.6 ± 20.1 years, and 56.8% were female. The main reasons for litigation were claimed inappropriate management (46.1%), misdiagnosis (22.6), and poor nursing care (8.3%). Significantly more litigations were filed against surgeons of the orthopedic subspecialty compared with trauma surgeons (78%; p ≤ 0.0001). There were significantly fewer litigations per 1000 cases filed overall in 2009-2017 (65% less; p = 0.003) than in 2000-2008. CONCLUSION: Our results could not confirm the often-stated trend of having more litigations against orthopedic and trauma surgeons. Although the absolute numbers increased, the number of litigations per 1000 patients treated declined. Patients who underwent elective surgery were more likely to file complaints than emergency patients.

Performance of a targeted cell-free DNA prenatal test for 22q11.2 deletion in a large clinical cohort.

OBJECTIVE: 22q11.2 deletion is more common than trisomies 18 and 13 combined, yet no routine approach to prenatal screening for this microdeletion has been established. This study evaluated the clinical sensitivity and specificity of a targeted cell-free DNA (cfDNA) test to screen for fetal 22q11.2 deletion in a large cohort, using blinded analysis of prospectively enrolled pregnancies and stored clinical samples. METHODS: In order to ensure that the analysis included a meaningful number of cases with fetal 22q11.2 deletion, maternal plasma samples were obtained by prospective, multicenter enrolment of pregnancies with a fetal cardiac abnormality and from stored clinical samples from a research sample bank. Fetal genetic status, as evaluated by microarray analysis, karyotyping with fluorescence in-situ hybridization or a comparable test, was available for all cases. Samples were processed as described previously for the Harmony prenatal test, with the addition of DANSR (Digital Analysis of Selected Regions) assays targeting the 3.0-Mb region of 22q11.2 associated with 22q11.2 deletion syndrome. Operators were blinded to fetal genetic status. Sensitivity and specificity of the cfDNA test for 22q11.2 deletion were calculated based on concordance between the cfDNA result and fetal genotype. RESULTS: The final study group consisted of 735 clinical samples, including 358 from prospectively enrolled pregnancies and 377 stored clinical samples. Of 46 maternal plasma samples from pregnancies with a 22q11.2 deletion, ranging in size from 1.25 to 3.25 Mb, 32 had a cfDNA result indicating a high probability of 22q11.2 deletion (sensitivity, 69.6% (95% CI, 55.2-80.9%)). All 689 maternal plasma samples without a 22q11.2 deletion were classified correctly by the cfDNA test as having no evidence of a 22q11.2 deletion (specificity, 100% (95% CI, 99.5-100%)). CONCLUSIONS: The results of this large-scale prospective clinical evaluation of the sensitivity and specificity of a targeted cfDNA test for fetal 22q11.2 deletion demonstrate that this test can detect the common and smaller, nested 22q11.2 deletions with a low (0-0.5%) false-positive rate. Although the positive predictive value (PPV) observed in this study population was 100%, the expected PPV in the general pregnant population is estimated to be 12.2% at 99.5% specificity and 41.1% at 99.9% specificity. The use of this cfDNA test to screen for 22q11.2 deletion could enhance identification of pregnancies at risk for 22q11.2 deletion syndrome without significantly increasing the likelihood of maternal anxiety and unnecessary invasive procedures related to a false-positive result. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mapping genes for phosphorus utilization and correlated traits using a 4k SNP linkage map in Japanese quail (Coturnix japonica).

A large F2 cross with 920 Japanese quail was used to map QTL for phosphorus utilization, calcium utilization, feed per gain and body weight gain. In addition, four bone ash traits were included, because it is known that they are genetically correlated with the focal trait of phosphorus utilization. Trait recording was done at the juvenile stage of the birds. The individuals were genotyped genome-wide for about 4k SNPs and a linkage map constructed, which agreed well with the reference genome. QTL linkage mapping was performed using multimarker regression analysis in a line cross model. Single marker association mapping was done within the mapped QTL regions. The results revealed several genome-wide significant QTL. For the focal trait phosphorus utilization, a QTL on chromosome CJA3 could be detected by linkage mapping, which was substantiated by the results of the SNP association mapping. Four candidate genes were identified for this QTL, which should be investigated in future functional studies. Some overlap of QTL regions for different traits was detected, which is in agreement with the corresponding genetic correlations. It seems that all traits investigated are polygenic in nature with some significant QTL and probably many other small-effect QTL that were not detectable in this study.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. METHODS: We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. RESULTS: Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. CONCLUSION: Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

COVID-19: public health management of the first two confirmed cases identified in the UK.

We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.

Prevalence of somatic and psychiatric morbidity across occupations in Switzerland and its correlation with suicide mortality: results from the Swiss National Cohort (1990-2014).

BACKGROUND: Suicide is a major and complex public health problem. In Switzerland, suicide accounts for about 1000 deaths yearly and is the fourth leading cause of mortality. The first nationwide Swiss study of suicides identified eight male and four female occupations with statistically significant excess of suicide compared to the general Swiss population. Working time, self-employer status, low socio-economic status and low skill level required for occupation were associated with increase in suicide risk. Presently, we aim to compare the distribution of suicide risk across occupations with the prevalence of somatic and psychiatric morbidity in Swiss working-aged adults. We hypothesized that some diseases would cluster in particular occupations, indicating potential work-relatedness of suicides found in these occupations. METHODS: We used the Swiss National Cohort (SNC) and included 10575 males and 2756 females deceased by suicide between 1990 and 2014. We estimated the prevalence of 16 categories of concomitant diseases in each occupation, using national mortality records, and assessed the homogeneity of diseases distribution across occupations. For diseases, which prevalence varied significantly across occupations, we analyzed the correlation with the distribution of suicide risk, estimated as the standardized mortality ratio (SMR) of suicide. RESULTS: Mental and behavioral disorders were the most commonly reported concomitant diseases in our population. In men, the prevalence of these disorders and more specifically, the prevalence of substance-related and addictive disorders, and of psychotic disorders varied significantly across occupations and was correlated with the SMR of suicide. The prevalence of malignant neoplasms and the prevalence of diseases of the musculoskeletal system and connective tissue also varied significantly across male occupations, while in women, such a variation was observed for neoplasms of uncertain or unknown behavior and diseases of the nervous system and sense organs, without being correlated with the SMR of suicide. CONCLUSION: Some of the identified morbidities can be occupation-related and could negatively affect the working capacity and the employability, which in turn could be related to the suicide. Disentangling concomitant diseases according to their work-relatedness and relationship with the suicide risk is important for identifying occupation-related suicides, understanding their characteristics, and developing appropriated interventions for their prevention.

[Lung ultrasonography in COVID-19 pneumonia]. / Sonographische Bildgebung der Lunge bei COVID-19.

BACKGROUND: Point-of-care ultrasound (POCUS) of the lung in patients with COVID-19 plays a key role in the emergency room and intensive care unit. Lung ultrasound is able to depict typical pulmonary findings of COVID-19 and is therefore suitable for diagnosis and follow-up of these patients. CLINICAL/METHODOLOGICAL ISSUE: Lung ultrasound in COVID-19 patients in the emergency room and intensive care unit. STANDARD RADIOLOGICAL METHODS: Computed tomography (low-dose CT) and X­ray of the lung. METHODOLOGICAL INNOVATIONS: Lung ultrasound in COVID-19 patients. RECOMMENDATIONS: Lung ultrasound in patients with COVID-19 offers similar performance as CT and is superior when compared to X­ray in evaluating pneumonia and acute respiratory distress syndrome (ARDS). Lung ultrasound plays an important role in the emergency room and intensive care unit. POCUS reduces exposure to radiation, therapy delays, and minimizes transport of high-risk patients. Differential diagnoses can also be clarified.

Unique Crystal Structure of Ca_{2}RuO_{4} in the Current Stabilized Semimetallic State.

The electric-current stabilized semimetallic state in the quasi-two-dimensional Mott insulator Ca_{2}RuO_{4} exhibits an exceptionally strong diamagnetism. Through a comprehensive study using neutron and x-ray diffraction, we show that this nonequilibrium phase assumes a crystal structure distinct from those of equilibrium metallic phases realized in the ruthenates by chemical doping, high pressure, and epitaxial strain, which in turn leads to a distinct electronic band structure. Dynamical mean field theory calculations based on the crystallographically refined atomic coordinates and realistic Coulomb repulsion parameters indicate a semimetallic state with partially gapped Fermi surface. Our neutron diffraction data show that the nonequilibrium behavior is homogeneous, with antiferromagnetic long-range order completely suppressed. These results provide a new basis for theoretical work on the origin of the unusual nonequilibrium diamagnetism in Ca_{2}RuO_{4}.

Studies of pear-shaped nuclei using accelerated radioactive beams.

There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.

Genomic analysis of perinatal sucking reflex in German Brown Swiss calves.

A healthy sucking reflex is essential for newborn calves to ensure sufficient colostrum intake in the first few hours postpartum. In recent decades, European Brown Swiss breeders have repeatedly reported that some calves lack the ability to consume colostrum directly after birth due to an absent sucking reflex. In this study, we collected the phenotypes of more than 5,500 German Brown Swiss calves and performed variance component estimation with sire threshold models using Markov chain Monte Carlo algorithms. The 50K (777K) genotypes of nearly 2,000 (200) calves were collected, and an imputation was performed for all 50K genotypes up to 777K. Genome-wide association studies (GWAS) for the trait sucking reflex were conducted for all 777K genotypes. Depending on the trait coding, a low heritability was estimated to range from 0.08 to 0.11. The GWAS results identified 34 trait-associated SNP on 6 different chromosomes. Post-GWAS analyses showed significant overrepresentation of Gene Ontologies for central nervous development and several regulative processes. Functional annotation clustering and pathway analysis revealed relations to lipid metabolism, immune and endocrine systems, and signal transduction. The results of this study suggest that breeding for an improved sucking reflex is possible but requires large data sets for the estimation of reliable breeding values (either large progeny testing groups or a large reference genome in a genomic selection program).

Acquisition of a Novel Sulfur-Oxidizing Symbiont in the Gutless Marine Worm Inanidrilus exumae.

Gutless phallodrilines are marine annelid worms without a mouth or gut, which live in an obligate association with multiple bacterial endosymbionts that supply them with nutrition. In this study, we discovered an unusual symbiont community in the gutless phallodriline Inanidrilus exumae that differs markedly from the microbiomes of all 22 of the other host species examined. Comparative 16S rRNA gene sequence analysis and fluorescence in situ hybridization revealed that I. exumae harbors cooccurring gamma-, alpha-, and deltaproteobacterial symbionts, while all other known host species harbor gamma- and either alpha- or deltaproteobacterial symbionts. Surprisingly, the primary chemoautotrophic sulfur oxidizer "Candidatus Thiosymbion" that occurs in all other gutless phallodriline hosts does not appear to be present in I. exumae Instead, I. exumae harbors a bacterial endosymbiont that resembles "Ca Thiosymbion" morphologically and metabolically but originates from a novel lineage within the class Gammaproteobacteria This endosymbiont, named Gamma 4 symbiont here, had a 16S rRNA gene sequence that differed by at least 7% from those of other free-living and symbiotic bacteria and by 10% from that of "Ca Thiosymbion." Sulfur globules in the Gamma 4 symbiont cells, as well as the presence of genes characteristic for autotrophy (cbbL) and sulfur oxidation (aprA), indicate that this symbiont is a chemoautotrophic sulfur oxidizer. Our results suggest that a novel lineage of free-living bacteria was able to establish a stable and specific association with I. exumae and appears to have displaced the "Ca Thiosymbion" symbionts originally associated with these hosts.IMPORTANCE All 22 gutless marine phallodriline species examined to date live in a highly specific association with endosymbiotic, chemoautotrophic sulfur oxidizers called "Ca Thiosymbion." These symbionts evolved from a single common ancestor and represent the ancestral trait for this host group. They are transmitted vertically and assumed to be in transition to becoming obligate endosymbionts. It is therefore surprising that despite this ancient, evolutionary relationship between phallodriline hosts and "Ca Thiosymbion," these symbionts are apparently no longer present in Inanidrilus exumae They appear to have been displaced by a novel lineage of sulfur-oxidizing bacteria only very distantly related to "Ca Thiosymbion." Thus, this study highlights the remarkable plasticity of both animals and bacteria in establishing beneficial associations: the phallodriline hosts were able to acquire and maintain symbionts from two very different lineages of bacteria, while sulfur-oxidizing bacteria from two very distantly related lineages were able to independently establish symbiotic relationships with phallodriline hosts.

Enhanced Quadrupole and Octupole Strength in Doubly Magic

The first 2^{+} and 3^{-} states of the doubly magic nucleus ^{132}Sn are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The ^{132}Sn ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a ^{206}Pb target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0_{g.s.}^{+}→2_{1}^{+}, 0_{g.s.}^{+}→3_{1}^{-}, and 2_{1}^{+}→3_{1}^{-} in ^{132}Sn. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0_{g.s.}^{+}→2_{1}^{+}) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of ^{132}Sn.

Accuracy and reproducibility of fetal-fraction measurement using relative quantitation at polymorphic loci with microarray.

OBJECTIVES: Various methods of fetal-fraction measurement have been employed in conjunction with different approaches to cell-free DNA testing for fetal aneuploidy. In this study, we determined the accuracy and reproducibility of fetal-fraction measurement using polymorphic assays that are incorporated into the test design as part of the Harmony® prenatal test and evaluated whether the single nucleotide polymorphisms selected for and used in these assays can be applied broadly to all patient populations. METHODS: Clinical maternal plasma samples were assayed using a custom microarray with Digital ANalysis of Selected Regions (DANSR) assays designed to cover non-polymorphic targets on chromosomes of interest for aneuploidy assessment (13, 18, 21, X and Y) and polymorphic targets for fetal-fraction assessment. In a consecutive series of 47 512 maternal plasma samples, fetal-fraction measurements based on polymorphic assays were compared with those from Y-sequence quantitation. Reproducibility was examined between first- and second-tube measurements for the same patient sample in 734 cases. The fraction of informative loci was calculated for 13 988 samples. RESULTS: There was a strong correlation between fetal fractions determined using the polymorphic assays and using Y-chromosome sequence quantitation (r = 0.97). Fetal-fraction measurement between the first and second tubes was highly reproducible (r = 0.98). The fraction of informative loci observed in a clinical series was consistent with predictions based on assay design. CONCLUSIONS: The method based on relative quantitation at polymorphic loci on a microarray is accurate and reproducible for fetal-fraction estimation and is equally informative across global populations. This study provides a useful benchmark for ensuring the reliability and accuracy of fetal-fraction measurement. © 2018 Roche Sequencing Solutions. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Association between fetal fraction on cell-free DNA testing and first-trimester markers for pre-eclampsia.

OBJECTIVES: To evaluate the association between fetal fraction on cell-free DNA (cfDNA) testing and first-trimester markers for pre-eclampsia, and to investigate the possible association of low fetal fraction with increased risks for pre-eclampsia (PE) and fetal growth restriction (FGR). METHODS: This was a retrospective cohort study including all women with a singleton pregnancy who had risk calculation for PE and FGR between 11 + 0 and 13 + 6 weeks' gestation and who also had cfDNA as a primary or secondary screening test for chromosomal abnormalities at any gestational age at two fetal medicine clinics in Sydney and Melbourne, Australia, between March 2013 and May 2017. Logarithmically transformed fetal fraction results were adjusted for gestational age and maternal characteristics. Associations with mean arterial pressure (MAP), mean uterine artery pulsatility index (UtA-PI), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), and risks for PE < 34 weeks, PE < 37 weeks and FGR < 37 weeks were analyzed using correlation analysis and univariable and multivariable linear regressions. RESULTS: In total, 4317 singleton pregnancies that underwent cfDNA testing with fetal fraction reported were included. Significant prediction of fetal fraction was provided by gestational age, conception by in-vitro fertilization, maternal age, body mass index, chronic hypertension, diabetes mellitus, South Asian ethnicity and being parous without history of PE or FGR. Fetal fraction was associated inversely with MAP and UtA-PI and associated positively with PAPP-A and PlGF. The lower the fetal fraction, the higher were the risks for PE < 34 weeks, PE < 37 weeks and FGR < 37 weeks (P < 0.001 for all). CONCLUSIONS: There is a significant association between fetal fraction result and first-trimester markers for adverse pregnancy outcome. Low fetal fraction is associated with an increased risk for pregnancy complication, but its capacity to act an as independent first-trimester marker in an algorithm for screening for PE and FGR requires further research. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial.

OBJECTIVE: This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS: Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT) ≤ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS: Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (> 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n = 87) and cases of fetal death and loss to follow-up (n = 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION: Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Mapping QTL for production traits in segregating Piétrain pig populations using genome-wide association study results of F2 crosses.

In this study, genome-wide association study (GWAS) results of porcine F2 crosses were used to map QTL in outcross Piétrain populations. For this purpose, two F2 crosses (Piétrain × Meishan, n = 304; Piétrain × Wild Boar, n = 291) were genotyped with the PorcineSNP60v2 BeadChip and phenotyped for the dressing yield, carcass length, daily gain and drip loss traits. GWASs were conducted in the pooled F2 cross applying single marker mixed linear models. For the investigated traits, between two and five (in total 15) QTL core regions, spanning 250 segregating SNPs around a significant trait-associated peak SNP, were identified. The SNPs within the QTL core regions were subsequently tested for trait association in two outcross Piétrain populations consisting of 771 progeny-tested boars and 210 sows with their own performance records. In the sow (boar) dataset, five (eight) of the 15 mapped QTL were validated. Hence, many QTL mapped in the F2 crosses (with Piétrain as a common founder breed) are still segregating in the current Piétrain breed. This confirms the usefulness of existing F2 crosses for mapping QTL that are still segregating in the recent founder breed generation. The approach utilizes the high power of an F2 cross to map QTL in a breeding population for which it is not guaranteed that they would be found using a GWAS in this population.