Understanding electrochemical interfaces through comparing experimental and computational charge density-potential curves.

Electrode-electrolyte interfaces play a decisive role in electrochemical charge accumulation and transfer processes. Theoretical modelling of these interfaces is critical to decipher the microscopic details of such phenomena. Different force field-based molecular dynamics protocols are compared here in a view to connect calculated and experimental charge density-potential relationships. Platinum-aqueous electrolyte interfaces are taken as a model. The potential of using experimental charge density-potential curves to transform cell voltage into electrode potential in force-field molecular dynamics simulations, and the need for that purpose of developing simulation protocols that can accurately calculate the double-layer capacitance, are discussed.

Genomic signatures of hybridization between Ixodes ricinus and Ixodes persulcatus in natural populations.

Identifying hybridization between common pathogen vectors is essential due to the major public health implications through risks associated with hybrid's enhanced pathogen transmission potential. The hard-ticks Ixodes ricinus and Ixodes persulcatus are the two most common vectors of tick-borne pathogens that affect human and animal health in Europe. Ixodes ricinus is a known native species in Finland with a well-known distribution, whereas I. persulcatus has expanded in range and abundance over the past 60 years, and currently it appears the most common tick species in certain areas in Finland. Here we used double-digest restriction site-associated DNA (ddRAD) sequencing on 186 ticks (morphologically identified as 92 I. ricinus, and 94 I. persulcatus) collected across Finland to investigate whether RAD generated single nucleotide polymorphisms (SNPs) can discriminate tick species and identify potential hybridization events. Two different clustering methods were used to assign specific species based on how they clustered and identified hybrids among them. We were able to discriminate between the two tick species and identified 11 putative hybrids with admixed genomic proportions ranging from approximately 24 to 76 percent. Four of these hybrids were morphologically identified as I. ricinus while the remaining seven were identified as I. persulcatus. Our results thus indicate that RAD SNPs are robust in identifying both species of the ticks as well as putative hybrids. These results further suggest ongoing hybridization between I. ricinus and I. persulcatus in their natural populations in Finland. The unique ability of RAD markers to discriminate between tick species and hybrids adds a useful aspect to tick evolutionary studies. Our findings align with previous studies and suggest a shared evolutionary history between the species, with instances of individuals possessing a considerable proportion of the other species' genome. This study is a significant step in understanding the formation of hybridization zones due to range expansion potentially associated with climate change.

Timing of induction of labor in suspected macrosomia: retrospective cohort study, systematic review and meta-analysis.

OBJECTIVE: Large-for-gestational-age (LGA) is associated with several adverse maternal and neonatal outcomes. Although many studies have found that early induction of labor (eIOL) in LGA reduces the incidence of shoulder dystocia (SD), no current guidelines recommend this particular strategy, due to concerns about increased rates of cesarean delivery (CD) and neonatal complications. The purpose of this study was to assess whether the timing of IOL in LGA fetuses affects maternal and neonatal outcomes in a single center; and to combine these results with the evidence reported in the literature. METHODS: This study comprised two parts. The first was a retrospective cohort study that included: consecutive patients with singleton pregnancy, an estimated fetal weight (EFW) ≥90th percentile on ultrasound (US) between 35+0 and 39+0 weeks of gestation (WG), who were eligible for normal vaginal delivery. The second part was a systematic review of literature and meta-analysis that included the results of the first part as well as all previously reported studies that have compared IOL to expectant management in patients with LGA. The perinatal outcomes were CD, operative vaginal delivery (OVD), SD, brachial plexus palsy, anal sphincter injury, postpartum hemorrhage (PPH), APGAR score, umbilical arterial pH, neonatal intensive care unit (NICU) admission, use of continuous positive airway pressure (CPAP), intracranial hemorrhage (ICH), phototherapy, and bone fracture. RESULTS: Retrospective cohort: of the 547 patients, 329 (60.1%) were induced and 218 (39.9%) entered spontaneous labor. Following covariate balancing, CD was significantly higher in the IOL group in comparison to the spontaneous labor group. This difference only became apparent beyond 40WG (hazard ratio: 1.9, p=0.030). The difference between both groups for shoulder dystocia was not statistically significant. Systematic review and metanalysis: 17 studies were included in addition to our own results giving a total sample size of 111,300 participants. When IOL was performed <40+0WG, the risk for SD was significantly lower in the IOL group (OR: 0.64, 95%CI: 0.42-0.98, I2 =19%). There was no significant difference in CD rate between IOL and expectant management after pooling the results of these 17 studies. However, when removing the studies in which IOL was done exclusively before 40+0WG, the risk for CD in the remaining studies (IOL not exclusively <40+0WG) was significantly higher in the IOL group (odds ratio [OR]: 1.46, 95% confidence interval [95%CI]: 1.02-2.09, I2 =56%). There were no statistically significant differences between IOL and expectant management for the remaining perinatal outcomes. Nulliparity, history of CD, and low Bishop score but not methods of induction were independent risk factors for intrapartum CD in patients who were induced for LGA. CONCLUSION: Timing of IOL in patients with suspected macrosomia significantly impacts perinatal adverse outcomes. IOL has no impact on rates of SD but does increase CD when considered irrespective of gestational age, but it may decrease the risk of SD without increasing the risk of other adverse maternal outcomes, in particular cesarean section when performed before 40+0 WG. (GRADE: Low/Very low). This article is protected by copyright. All rights reserved.

Prediction of large-for-gestational age at 36 weeks' gestation: two-dimensional ultrasound vs three-dimensional ultrasound vs magnetic resonance imaging.

OBJECTIVE: To compare the performance of two-dimensional ultrasound (2D-US), three-dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) at 36 weeks' gestation in predicting the delivery of a large-for-gestational-age (LGA) neonate, defined as birth weight ≥ 95th percentile, in patients at high and low risk for macrosomia. METHODS: This was a secondary analysis of a prospective observational study conducted between January 2017 and February 2019. Women with a singleton pregnancy at 36 weeks' gestation underwent 2D-US, 3D-US and MRI within 15 min for estimation of fetal weight. Weight estimations and birth weight were plotted on a growth curve to obtain percentiles for comparison. Participants were considered high risk if they had at least one of the following risk factors: diabetes mellitus, estimated fetal weight ≥ 90th percentile at the routine third-trimester ultrasound examination, obesity (prepregnancy body mass index ≥ 30 kg/m2) or excessive weight gain during pregnancy. The outcome was the diagnostic performance of each modality in the prediction of birth weight ≥ 95th percentile, expressed as the area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity and positive and negative predictive values. RESULTS: A total of 965 women were included, of whom 533 (55.23%) were high risk and 432 (44.77%) were low risk. In the low-risk group, the AUCs for birth weight ≥ 95th percentile were 0.982 for MRI, 0.964 for 2D-US and 0.962 for 3D-US; pairwise comparisons were non-significant. In the high-risk group, the AUCs were 0.959 for MRI, 0.909 for 2D-US and 0.894 for 3D-US. A statistically significant difference was noted between MRI and both 2D-US (P = 0.002) and 3D-US (P = 0.002), but not between 2D-US and 3D-US (P = 0.503). In the high-risk group, MRI had the highest sensitivity (65.79%) compared with 2D-US (36.84%, P = 0.002) and 3D-US (21.05%, P < 0.001), whereas 3D-US had the highest specificity (98.99%) compared with 2D-US (96.77%, P = 0.005) and MRI (96.97%, P = 0.004). CONCLUSIONS: At 36 weeks' gestation, MRI has better performance compared with 2D-US and 3D-US in predicting birth weight ≥ 95th percentile in patients at high risk for macrosomia, whereas the performance of 2D-US and 3D-US is comparable. For low-risk patients, the three modalities perform similarly. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Effect of cannula insertion site during fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm prelabor rupture of membranes.

OBJECTIVE: To assess whether the cannula insertion site on the maternal abdomen during fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was associated with preterm prelabor rupture of membranes (PPROM) before balloon removal. METHODS: This was a multicenter retrospective study of consecutive pregnancies with isolated left- or right-sided CDH that underwent FETO in four centers between January 2009 and January 2021. The site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups to calculate an average treatment effect (ATE) by inverse probability of treatment weighting. Logistic regression and Cox proportional hazard regression including the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM before balloon removal. RESULTS: A total of 294 patients were included. The mean ± SD gestational age at PPROM was 33.45 ± 2.01 weeks and the mean rate of PPROM before balloon removal was 25.9% (76/294). Gestational age at FETO was later in the below-umbilicus group (mean ± SD, 29.47 ± 1.29 weeks vs 29.00 ± 1.25 weeks; P = 0.002) and the duration of FETO was longer in the above-umbilicus group (median, 14.49 min (interquartile range (IQR), 8.00-21.00 min) vs 11.00 min (IQR, 7.00-14.49 min); P = 0.002). After balancing for possible confounding factors, trocar entry point below the umbilicus did not increase the risk of PPROM before balloon removal (adjusted odds ratio, 1.56 (95% CI, 0.89-2.74); P = 0.120) and had no effect on the timing of PPROM before balloon removal (adjusted hazard ratio, 1.56 (95% CI, 0.95-2.55); P = 0.080). CONCLUSION: There was no evidence that uterine entry site for FETO was correlated with the risk of PPROM before balloon removal. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Crowdsourced tick observation data from across 60 years reveals major increases and northwards shifts in tick contact areas in Finland.

There is mounting evidence of increases in tick (Acari: Ixodidae) contacts in Finland during the past few decades, highlighted by increases in the incidence of Lyme borreliosis and tick-borne encephalitis (TBE). While nationwide field studies to map distributions of ticks are not feasible, crowdsourcing provides a comprehensive method with which to assess large-scale changes in tick contact areas. Here, we assess changes in tick contact areas in Finland between 1958 and 2021 using three different nationwide crowdsourced data sets. The data revealed vast increases in tick contact areas, with ticks estimated to be contacted locally approximately 400 km further north in western and approximately 100 km further north in eastern Finland in 2021 than 1958. Tick contact rates appeared to be highest along the coastline and on the shores of large lakes, possibly indicating higher tick abundance therein. In general, tick observations per inhabitant increased from 2015 to 2021. Tick contact areas have expanded in Finland over the past 60 years. It appears that taiga ticks (Ixodes persulcatus) are behind most of the northwards shifts in tick contact areas, with Ixodes ricinus contributing mostly to new contact areas in the south. While ticks are now present in most of Finland, there are still areas where tick abundance is low and/or establishment not possible, mainly in northern Finland.

Prevalence of and risk factors for failure of fetal magnetic resonance imaging due to maternal claustrophobia or malaise.

OBJECTIVE: To evaluate the prevalence of and risk factors for failure of fetal magnetic resonance imaging (MRI) due to maternal claustrophobia or malaise. METHODS: This retrospective cohort study included pregnant women who underwent fetal MRI for clinical indications or research purposes between January 2012 and December 2019 at a single center. One group included patients who completed the entire examination and the other group inlcuded patients who interrupted their MRI examination due to claustrophobia/malaise. We estimated the rate of MRI failure due to maternal claustrophobia/malaise and compared maternal and clinical variables between the two groups. Multiple logistic regression analysis was performed to identify independent risk factors for claustrophobia/malaise during MRI examination in pregnancy. RESULTS: Among 3413 patients who agreed to undergo fetal MRI, the prevalence of failure because of claustrophobia or malaise was 2.1%. The rate of claustrophobia/malaise in patients who underwent MRI for a clinical indication was lower compared to that in patients who underwent MRI for research purposes only (0.6% (4/696) vs 2.4% (65/2678); P = 0.003). Fetal MRI performed for research purposes only (adjusted odds ratio (aOR), 0.05 (95% CI, 0.01-0.48); P = 0.003), higher maternal age (aOR, 1.07 (95% CI, 1.02-1.12); P = 0.003) and later gestational age at the time of fetal MRI (aOR, 1.46 (95% CI, 1.16-2.04); P = 0.008) were independent risk factors for claustrophobia/malaise. Shorter fetal MRI duration (aOR, 0.77 (95% CI, 0.63-0.88); P = 0.001) was also associated with claustrophobia/malaise during the procedure. Body mass index, ethnic origin, multiple pregnancy, being parous and size of the magnetic bore were not associated with MRI failure due to claustrophobia/malaise. CONCLUSION: The rate of fetal MRI failure due to claustrophobia or malaise was found to be low, particularly when the examination was performed for a clinical indication, and should not be considered a common problem in the pregnant population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Voles, shrews and red squirrels as sources of tick blood meals and tick-borne pathogens on an island in southwestern Finland.

Molecular identification of the previous blood meal source of a questing tick (Acari: Ixodidae) from blood meal fragments was proposed a few decades ago. Following this, several blood meal assays have been developed and published, but none of them have been taken into widespread use. Recently, novel retrotransposon-based qPCR assays designed for detecting blood meal fragments of North American host species were published. We wanted to assess their function with host species present in Finland. Questing ticks were collected by cloth dragging in August-September 2021 from an island in southwestern Finland. DNA was extracted from Ixodes ricinus nymphs (n=438) and qPCR assays applied to identify larval blood meal sources (voles, shrews and red squirrels) and screen for several tick-borne human pathogens and other microbes with pathogenic potential [Borrelia spp. (including specific assays for Borrelia afzelii, Borrelia garinii, Borrelia valaisiana), Anaplasma phagocytophilum, Babesia spp., Rickettsia spp., and Neoehrlichia mikurensis]. The probability of a nymph having fed as larva on either a vole, shrew or red squirrel was 0.34 (0.30 - 0.38; 95% confidence interval). Bacteria of the genus Borrelia were the most common pathogens detected, with host-specific probabilities of carrying Borrelia of 0.30 (0.18 - 0.44) for nymphs that had fed on voles, 0.23 (0.14 - 0.35) for nymphs that had fed on shrews, and 0.42 (0.28 - 0.58) for nymphs that had fed on red squirrels. Other microbes were rarely acquired from these hosts, apart from N. mikurensis from voles. This study highlights that shrews and red squirrels may equal voles as blood meal sources for I. ricinus larvae. Overall, variation in proportions of blood meals provided by these animals may be high across even proximate study areas. All studied host species appeared to be important sources for particularly Borrelia afzelii, and voles also for N. mikurensis.

Treatment Strategy for Rifampin-Susceptible Tuberculosis.

BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.).

Does environmental adaptation or dispersal history explain the geographical distribution of Ixodes ricinus and Ixodes persulcatus ticks in Finland?

In Finland, the distribution area of the taiga tick, Ixodes persulcatus (Schulze, 1930), is nested within a broader area of distribution of a congeneric species, the sheep tick, Ixodes ricinus (Linnaeus, 1758) (Acari: Ixodidae). We assess whether distinct environmental adaptations or dispersal history provides a more parsimonious explanation for the differences in the distributions of the two common and medically important ixodids in Finland. We used an innovative spatially constrained randomization procedure to analyze whether crowdsourced occurrence data points of the two tick species had statistically different associations with any of the 28 environmental variables. Using points of presence in a region of species co-occurrence, we built Maxent models to examine whether environmental factors or dispersal history could explain the absence of I. persulcatus in a part of the range of I. ricinus in Finland. Five environmental variables-number of inhabitants, road length, elevation above sea level, proportion of barren bedrock and boulders, and proportion of unsorted glacial deposits-were significant at p ≤ .05, indicating greater between-species difference in original than in the randomized data. Of these variables, only the optimum value for unsorted glacial deposits was higher for I. persulcatus than for I. ricinus. Maxent models also predicted high relative habitat suitability (suitability >80%) for I. persulcatus south of its current, sharply bounded distribution range, suggesting that the species has not fulfilled its distribution potential in Finland. The two most common and medically relevant ixodids in Finland may colonize habitats with different environmental conditions. On the contrary, the recent establishment and ongoing dispersion of I. persulcatus in Fennoscandia rather than environmental conditions cause the southernmost distribution limit of the species in Finland.

Predicting habitat suitability for Ixodes ricinus and Ixodes persulcatus ticks in Finland.

BACKGROUND: Ticks are responsible for transmitting several notable pathogens worldwide. Finland lies in a zone where two human-biting tick species co-occur: Ixodes ricinus and Ixodes persulcatus. Tick densities have increased in boreal regions worldwide during past decades, and tick-borne pathogens have been identified as one of the major threats to public health in the face of climate change. METHODS: We used species distribution modelling techniques to predict the distributions of I. ricinus and I. persulcatus, using aggregated historical data from 2014 to 2020 and new tick occurrence data from 2021. By aiming to fill the gaps in tick occurrence data, we created a new sampling strategy across Finland. We also screened for tick-borne encephalitis virus (TBEV) and Borrelia from the newly collected ticks. Climate, land use and vegetation data, and population densities of the tick hosts were used in various combinations on four data sets to estimate tick species' distributions across mainland Finland with a 1-km resolution. RESULTS: In the 2021 survey, 89 new locations were sampled of which 25 new presences and 63 absences were found for I. ricinus and one new presence and 88 absences for I. persulcatus. A total of 502 ticks were collected and analysed; no ticks were positive for TBEV, while 56 (47%) of the 120 pools, including adult, nymph, and larva pools, were positive for Borrelia (minimum infection rate 11.2%, respectively). Our prediction results demonstrate that two combined predictor data sets based on ensemble mean models yielded the highest predictive accuracy for both I. ricinus (AUC = 0.91, 0.94) and I. persulcatus (AUC = 0.93, 0.96). The suitable habitats for I. ricinus were determined by higher relative humidity, air temperature, precipitation sum, and middle-infrared reflectance levels and higher densities of white-tailed deer, European hare, and red fox. For I. persulcatus, locations with greater precipitation and air temperature and higher white-tailed deer, roe deer, and mountain hare densities were associated with higher occurrence probabilities. Suitable habitats for I. ricinus ranged from southern Finland up to Central Ostrobothnia and North Karelia, excluding areas in Ostrobothnia and Pirkanmaa. For I. persulcatus, suitable areas were located along the western coast from Ostrobothnia to southern Lapland, in North Karelia, North Savo, Kainuu, and areas in Pirkanmaa and Päijät-Häme. CONCLUSIONS: This is the first study conducted in Finland that estimates potential tick species distributions using environmental and host data. Our results can be utilized in vector control strategies, as supporting material in recommendations issued by public health authorities, and as predictor data for modelling the risk for tick-borne diseases.

Ticks (Acari: Ixodidae) parasitizing migrating and local breeding birds in Finland.

Ticks are globally renowned vectors for numerous zoonoses, and birds have been identified as important hosts for several species of hard ticks (Acari: Ixodidae) and tick-borne pathogens. Many European bird species overwinter in Africa and Western Asia, consequently migrating back to breeding grounds in Europe in the spring. During these spring migrations, birds may transport exotic tick species (and associated pathogens) to areas outside their typical distribution ranges. In Finland, very few studies have been conducted regarding ticks parasitizing migrating or local birds, and existing data are outdated, likely not reflecting the current situation. Consequently, in 2018, we asked volunteer bird ringers to collect ticks from migrating and local birds, to update current knowledge on ticks found parasitizing birds in Finland. In total 430 ticks were collected from 193 birds belonging to 32 species, caught for ringing between 2018 and 2020. Furthermore, four Ixodes uriae were collected from two roosting islets of sea birds in 2016 and 2020. Ticks collected on birds consisted of: Ixodes ricinus (n = 421), Ixodes arboricola (4), Ixodes lividus (2) and Hyalomma marginatum (3). Ixodes ricinus loads (nymphs and larvae) were highest on thrushes (Passeriformes: Turdidae) and European robins (Erithacus rubecula). The only clearly imported exotic tick species was H. marginatum. This study forms the second report of both I. uriae and I. arboricola from Finland, and possibly the northernmost observation of I. arboricola from Europe. The importation of exotic tick species by migrating birds seems a rare occurrence, as over 97% of all ticks collected from birds arriving in Finland during their spring migrations were I. ricinus, a species native to and abundant in Finland.

Absence of Francisella tularensis in Finnish Ixodes ricinus and Ixodes persulcatus ticks.

Francisella tularensis subsp. holarctica is the causative agent of tularaemia in Europe. Finland is a high-incidence region for tularaemia, with mosquito bites as the most common sources of infection. However, in Central and Western Europe, ticks (Acari: Ixodidae) have been suggested as the main vectors. Indeed, several studies have reported the pathogen from the locally most common human-biting tick species, Ixodes ricinus. In Finland, the occurrence of the pathogen in ticks has started receiving attention only recently. Here, we collate previous tick screening data from Finland regarding F. tularensis as well as present the results from a novel screening of roughly 15 000 I. ricinus and I. persulcatus collected from across the country. In total, 14 878 ticks collected between 2015 and 2020 were screened for F. tularensis using a TaqMan-based qPCR assay targeting the 23 KDa gene. The combined screening efforts of the current and previous studies, encompassing roughly 20 000 ticks, did not find any positive ticks. Given the negative results despite the considerable sample size, it appears that the pathogen is not circulating in local tick populations in Finland. We discuss some possible reasons for the lack of the bacterium in ticks in this high-incidence region of tularaemia.

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.

Cell-free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10-14 weeks and meta-analysis.

OBJECTIVE: To expand the limited knowledge on cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy by updating the data from The Fetal Medicine Foundation (FMF) on prospective first-trimester screening and those identified in a systematic review of the literature. METHODS: The FMF data were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation using the Harmony® prenatal test. A search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov and the International Clinical Trials Registry Platform (World Health Organization) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancy, irrespective of gestational age at testing, in which data on pregnancy outcome were provided for at least 85% of the study population. Meta-analysis was performed using the FMF data and data from the studies identified by the literature search. This review was registered in the PROSPERO international database for systematic reviews RESULTS: In the FMF study, cfDNA testing was carried out in 1442 twin pregnancies and a result was obtained, after first or second sampling, in 1367 (94.8%) cases. In 93.1% (1272/1367) of cases, there was prenatal or postnatal karyotyping or birth of phenotypically normal babies; 95 cases were excluded from further analysis either because the pregnancy ended in termination, miscarriage or stillbirth with no known karyotype (n = 56) or there was loss to follow-up (n = 39). In the 1272 pregnancies included in the study, there were 20 cases with trisomy 21, 10 with trisomy 18, two with trisomy 13 and 1240 without trisomy 21, 18 or 13. The cfDNA test classified correctly 19 (95.0%) of the 20 cases of trisomy 21, nine (90.0%) of the 10 cases of trisomy 18, one (50.0%) of the two cases of trisomy 13 and 1235 (99.6%) of the 1240 cases without any of the three trisomies. The literature search identified 12 relevant studies, excluding our papers because their data are included in the current study. In the combined populations of our study and the 12 studies identified by the literature search, there were 137 trisomy-21 and 7507 non-trisomy-21 twin pregnancies; the pooled weighted detection rate (DR) and false-positive rate (FPR) were 99.0% (95% CI, 92.0-99.9%) and 0.02% (95% CI, 0.001-0.43%), respectively. In the combined total of 50 cases of trisomy 18 and 6840 non-trisomy-18 pregnancies, the pooled weighted DR and FPR were 92.8% (95% CI, 77.6-98.0%) and 0.01% (95% CI, 0.00-0.44%), respectively. In the combined total of 11 cases of trisomy 13 and 6290 non-trisomy-13 pregnancies, the pooled weighted DR and FPR were 94.7% (95% CI, 9.14-99.97%) and 0.10% (95% CI, 0.03-0.39%), respectively. CONCLUSIONS: In twin pregnancy, the reported DR of trisomy 21 by cfDNA testing is high, but lower than that in singleton pregnancy, whereas the FPR appears to be equally low. The number of cases of trisomy 18 and more so trisomy 13 was too small for accurate assessment of the predictive performance of the cfDNA test. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Magnetic resonance scoring system for assessment of adnexal masses: added value of diffusion-weighted imaging including apparent diffusion coefficient map.

OBJECTIVES: To validate prospectively the ADNEX magnetic resonance (MR) scoring system to assess adnexal masses and to evaluate a new, modified ADNEX MR scoring system that incorporates diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping. METHODS: Between January 2015 and September 2018, 323 consecutive women with adnexal masses diagnosed on transvaginal ultrasound (TVS) underwent standardized MR imaging (MRI) including diffusion and dynamic contrast-enhanced sequences. Of these, 131 underwent subsequent surgery. For interpretation of the MRI examinations, we applied the five-category ADNEX MR scoring system, along with a modified scoring system including DWI with ADC mapping. For both scoring systems, a score was given for all adnexal masses. Histological diagnosis was considered as the gold standard and lesions were classified as benign or malignant. The difference between the predictive values for diagnosing malignancy of the classical and modified scoring systems was assessed on the basis of the areas under the receiver-operating-characteristics (AUC) curves. The sensitivity and specificity for diagnosing malignancy of each score were also calculated. RESULTS: Among the 131 women with adnexal mass(es) diagnosed on TVS who underwent MRI and subsequent surgery, the surgery revealed 161 adnexal masses in 126 women; five women had no mass. Histological examination confirmed 161 adnexal masses, of which all had been detected on MRI: 32 malignant tumors, 15 borderline tumors, which were classified as part of the malignant group (n = 47), and 114 benign lesions. The AUC for prediction of a malignant lesion was 0.938 (95% CI, 0.902-0.975) using the classical ADNEX MR scoring system and 0.974 (95% CI, 0.953-0.996) using the modified scoring system. Pairwise comparison of these AUCs revealed a significant difference (P = 0.0032). The sensitivity and specificity for diagnosing malignancy with an ADNEX MR score of 4 or more were 95.5% and 86.6%, respectively, using the classic scoring system, and 95.7% and 93.3%, respectively, using the modified scoring system. CONCLUSION: DWI with ADC mapping could be integrated into the ADNEX MR scoring system to improve specificity, thereby potentially optimizing clinical management by avoiding unnecessary surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal stomach position predicts gastrointestinal morbidity at 2 years in fetuses with left-sided congenital diaphragmatic hernia.

OBJECTIVE: The long-term morbidity associated with isolated left-sided congenital diaphragmatic hernia (CDH) has been described previously. However, antenatal criteria impacting gastrointestinal morbidity (GIM) are not yet defined. The objective of this study was to evaluate the effect of fetal stomach position on the risk of GIM at 2 years of age in children with left-sided CDH. METHODS: This was a retrospective, observational multicenter cohort study of data obtained from January 2010 to January 2014, that included patients whose fetus had isolated left-sided CDH, with or without fetal endoscopic tracheal occlusion (FETO). Prenatal maternal, fetal and pediatric data were collected. Fetal stomach position was evaluated a posteriori by two observers, using ultrasound images at the level of the four-chamber view of the heart that had been obtained to calculate the observed-to-expected lung-area-to-head-circumference ratio (O/E-LHR). Fetal stomach position was graded as follows: Grade 1, stomach not visualized; Grade 2, stomach visualized anteriorly, next to the apex of the heart, with no structure in between the stomach and the sternum; Grade 3, stomach visualized alongside the left ventricle of the heart, and abdominal structures anteriorly; or Grade 4, as Grade 3 but with stomach posterior to the level of the atrioventricular heart valves. The primary outcome was GIM at 2 years of age, assessed in a composite manner, including the occurrence of gastroesophageal reflux disease, need for gastrostomy, duration of parenteral and enteral nutrition and persistence of oral aversion. Regression analysis was performed in order to investigate the effect of O/E-LHR, stomach position and FETO on various GIM outcome variables. RESULTS: Forty-seven patients with fetal left-sided CDH were included in the analysis. Thirteen (27.7%) infants did not meet the criterion of exclusive oral feeding at 2 years of age. Fetal stomach position grade was associated significantly and independently with the duration of parenteral nutrition (odds ratio (OR), 19.86; P = 0.031) and persistence of oral aversion at 2 years (OR, 3.40; P = 0.006). On multivariate analysis, O/E-LHR was predictive of the need for prosthetic patch repair, but not for GIM. FETO did not seem to affect the risk of GIM at 2 years. CONCLUSION: In isolated left-sided CDH, fetal stomach position is the only factor that is predictive of GIM at 2 years of age. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Molecular detection and phylogenetic analysis of Borrelia miyamotoi strains from ticks collected in the capital region of Finland.

Borrelia miyamotoi is an emerging pathogen that shares high similarity with relapsing fever Borrelia, but has an atypical clinical presentation. Within the framework of tick-borne disease surveillance in Finland, human serum samples suspected for tick-borne encephalitis (n=974) and questing ticks (n=739) were collected from the capital region in Finland to determine the prevalence of B. miyamotoi. All tested human samples were negative and 5 (0.68 %) Ixodes ricinus ticks were positive for B. miyamotoi. Partial sequencing of the flagellin (flaB) gene of 3 positive samples and 27 B. miyamotoi-positive tick samples obtained from previous studies across Finland were amplified, sequenced, and included in the phylogenetic analysis. The phylogenetic tree revealed that most B. miyamotoi strains isolated from ticks in Finland share high similarity with other European strains, including strains related to human infection. Possible disease transmission may occur during exposure to tick bites. A single strain collected from an I. persulcatus tick in Pajujärvi grouped with an outlier of B. miyamotoi strains isolated from Russia and Far East Asian countries. Further studies should investigate the pathogen's role in human infection in Finland. Another important finding is the occurrence of I. persulcatus ticks (8%) collected by crowdsourcing from the coastal southern part of Finland. This suggests a regular introduction and a possible wide expansion of this tick species in the country. This could be associated with transmission of new pathogens.