Detection of fetal cardiac anomalies: cost-effectiveness of increased number of cardiac views.

OBJECTIVE: To compare the recommended three-view fetal heart screening method to detect major congenital heart disease (CHD) with more elaborate screening strategies to determine the cost-effective strategy in unselected (low-risk) pregnancies. METHODS: A decision-analytic model was designed to compare four screening strategies to identify fetuses with major CHD in a theoretical cohort of 4 000 000 births in the USA. The four strategies were: (1) three views: four-chamber view (4CV) and views of the left (LVOT) and right (RVOT) ventricular outflow tracts; (2) five views: 4CV, LVOT, RVOT and longitudinal views of the ductal arch and aortic arch; (3) five axial views: 4CV, LVOT, RVOT, three-vessel (3V) view and three-vessels-and-trachea view; and (4) six views: 4CV, LVOT, RVOT and 3V views and longitudinal views of the ductal arch and aortic arch. Outcomes related to neonatal mortality and neurodevelopmental disability were evaluated. The analysis was performed from a healthcare-system perspective, with a cost-effectiveness willingness-to-pay threshold set at $100 000 per quality-adjusted life year (QALY). Baseline analysis, one-way sensitivity analysis and Monte-Carlo simulation were performed. RESULTS: In our baseline model, screening with five axial views was the optimal strategy, detecting 3520 more CHDs, and resulting in 259 fewer children with neurodevelopmental disability, 40 fewer neonatal deaths and only slightly higher costs, compared with screening with the currently recommended three views. Screening with six views was more effective, but also cost considerably more, compared with screening with five axial views, and had an incremental cost of $490 023/QALY, which was over the willingness-to-pay threshold. The five-view strategy was dominated by the other three strategies, i.e. it was more costly and less effective in comparison. The data were robust when tested with Monte-Carlo and one-way sensitivity analysis. CONCLUSION: Although current guidelines recommend a minimum of three views for detecting CHD during the mid-trimester anatomy scan, screening with five axial views is a cost-effective strategy that may lead to improved outcome compared with three-view screening. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Impact of maternal obesity on fetal cardiac screening: which follow-up strategy is cost-effective?

OBJECTIVE: To perform a cost-effectiveness analysis of different follow-up strategies for non-obese and obese women who had incomplete fetal cardiac screening for major congenital heart disease (CHD). METHODS: Three decision-analytic models, one each for non-obese, obese and Class-III-obese women, were developed to compare five follow-up strategies for initial suboptimal fetal cardiac screening. The five strategies were: (1) no follow-up ultrasound (US) examination but direct referral to fetal echocardiography (FE); (2) one follow-up US, then FE if fetal cardiac views were still suboptimal; (3) up to two follow-up US, then FE if fetal cardiac views were still suboptimal; (4) one follow-up US and no FE; and (5) up to two follow-up US and no FE. The models were designed to identify fetuses with major CHD in a theoretical cohort of 4 000 000 births in the USA. Outcomes related to neonatal mortality and neurodevelopmental disability were evaluated. A cost-effectiveness willingness-to-pay threshold was set at US$100 000 per quality-adjusted life year (QALY). Base-case and sensitivity analysis and Monte-Carlo simulation were performed. RESULTS: In our base-case models for all body mass index (BMI) groups, no follow-up US, but direct referral to FE led to the best outcomes, detecting 7%, 25% and 82% more fetuses with CHD in non-obese, obese and Class-III-obese women, respectively, compared with the baseline strategy of one follow-up US and no FE. However, no follow-up US, but direct referral to FE was above the US$100 000/QALY threshold and therefore not cost-effective. The cost-effective strategy for all BMI groups was one follow-up US and no FE. Both up to two follow-up US with no FE and up to two follow-up US with FE were dominated (being more costly and less effective), while one follow-up US with FE was over the cost-effectiveness threshold. One follow-up US and no FE was the optimal strategy in 97%, 93% and 86% of trials in Monte-Carlo simulation for non-obese, obese and Class-III-obese models, respectively. CONCLUSION: For both non-obese and obese women with incomplete fetal cardiac screening, the optimal CHD follow-up screening strategy is no further US and immediate referral to FE; however, this strategy is not cost-effective. Considering costs, one follow-up US and no FE is the preferred strategy. For both obese and non-obese women, Monte-Carlo simulations showed clearly that one follow-up US and no FE was the optimal strategy. Both non-obese and obese women with initial incomplete cardiac screening examination should therefore be offered one follow-up US. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Neurodevelopmental disorder in children believed to have isolated mild ventriculomegaly prenatally.

OBJECTIVE: To estimate the prevalence of specific neurodevelopmental disorders in children believed to have isolated mild ventriculomegaly (IMV) prenatally in the second trimester of pregnancy, in order to optimize the counseling process. METHODS: This was a nationwide registry-based study including all singleton pregnancies that had first- and second-trimester ultrasound scans in the period 1st January 2008 to 1st October 2014, identified in the Danish Fetal Medicine Database and local clinical databases in Denmark. All fetuses diagnosed prenatally with IMV (measurement of the atrium of the lateral ventricles, 10.0-15.0 mm) between 18 and 22 weeks' gestation were followed up in national patient registers until the age of 2-7 years. Information was obtained on the diagnoses of intellectual disability, cerebral palsy, autism spectrum disorder, epilepsy and impaired psychomotor development. Neurodevelopmental disorders were compared between those with postnatally confirmed IMV and a reference population of children in the same age range. RESULTS: Of a cohort of 292 046 fetuses, 133 were found to have apparent IMV on the second-trimester scan for fetal malformations. In 11 cases, long-term follow-up was not possible owing to termination of pregnancy, spontaneous miscarriage, neonatal death or loss to follow-up. Of the 122 liveborn children followed up until 2-7 years, 15 were identified as having an additional abnormality while 107 were confirmed postnatally to have IMV. Of these 107 children, the diagnosis of a neurodevelopmental disorder was registered in six (5.6%), corresponding to an odds ratio of 2.64 (95% CI, 1.16-6.02), as compared with the reference population. The diagnoses were autism spectrum disorder, epilepsy and impaired psychomotor development. None of these 107 children was diagnosed with intellectual disability or cerebral palsy. CONCLUSIONS: Our results show that a confirmed diagnosis of IMV was associated with an increased risk of a neurodevelopmental disorder, as compared with the reference population, but the absolute risk was low and there were no cases of intellectual disability or cerebral palsy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Trastorno del desarrollo neurológico en fetos con sospecha de ventriculomegalia leve aislada prenatal OBJETIVO: Estimar la prevalencia de trastornos específicos del desarrollo neurológico en fetos con sospecha de ventriculomegalia leve aislada (IMV, por sus siglas en inglés) prenatal en el segundo trimestre del embarazo, a fin de optimizar el proceso de asesoramiento. MÉTODOS: Este estudio estuvo basado en un registro nacional que incluyó todos los embarazos con feto único a los que se les hizo ecografías en el primer y segundo trimestre entre el 1 de enero de 2008 y el 1 de octubre de 2014, identificados en la Base de Datos Danesa de Medicina Fetal y en las bases de datos clínicas locales en Dinamarca. Todos los fetos diagnosticados prenatalmente con IMV (por medición de la aurícula de los ventrículos laterales, 10,0-15,0 mm) entre las semanas de gestación 18 y 22 fueron monitoreados en los registros nacionales de pacientes hasta la edad de 2-7 años. Se obtuvo información sobre los diagnósticos de discapacidad intelectual, parálisis cerebral, trastornos del espectro autista, epilepsia y trastornos del desarrollo psicomotor. Se compararon los trastornos del desarrollo neurológico entre aquellos con IMV confirmada después del nacimiento y una población de referencia de niños en el mismo rango de edad. RESULTADOS: De una cohorte de 292 046 fetos, se encontró que 133 tenían IMV aparente en la ecografía del segundo trimestre realizada para detectar malformaciones fetales. El seguimiento a largo plazo no fue posible en 11 casos debido a la interrupción del embarazo, el aborto espontáneo, la muerte del recién nacido o el abandono del monitoreo. De los 122 niños nacidos vivos a los que se les dio seguimiento hasta los 2-7 años, se identificó a 15 con una anomalía adicional, mientras que a 107 se les confirmó postnatalmente que tenían IMV. De estos 107 niños, se registró el diagnóstico de un trastorno del desarrollo neurológico en seis (5,6%), lo que corresponde a una razón de momios de 2,64 (IC 95%: 1,16-6,02), en comparación con la población de referencia. Los diagnósticos fueron trastornos del espectro autista, epilepsia y trastornos del desarrollo psicomotor. Ninguno de estos 107 niños fue diagnosticado con discapacidad intelectual o parálisis cerebral. CONCLUSIONES: Nuestros resultados muestran que un diagnóstico confirmado de IMV se asoció con un mayor riesgo de trastorno del desarrollo neurológico, en comparación con la población de referencia, pero que el riesgo absoluto fue bajo y no hubo casos de discapacidad intelectual o parálisis cerebral.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.

Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.

Ovarian tumor-induced T cell suppression is alleviated by vascular leukocyte depletion.

The ovarian cancer microenvironment recruits an array of immune cells to the site of tumor growth. Within the peritoneal ascites of both humans and mice, the predominant population of tumor-infiltrating leukocytes is a CD11c(+)CD11b(+) population variably referred to as vascular leukocytes (VLCs), tumor-associated macrophages, and immature dendritic cells. We have previously shown that these cells are critical for tumor growth because their selective elimination from the peritoneal tumor microenvironment inhibited tumor progression. However, the underlying mechanism by which this therapy was efficacious is poorly understood. Here, we use the murine ID8 ovarian tumor model to demonstrate that the tumor microenvironment induces in vivo immunosuppression of T cells and that the SR-A(+) VLCs mediate this suppression. Importantly, the elimination of SR-A(+) VLCs from the peritoneum of tumor-bearing mice relieves the T cell suppression. Moreover, the profound changes that VLC elimination has on the immune system are T cell-dependent because the protective antitumor effect of VLC elimination does not occur when CD8 T cells are concomitantly depleted. These results were confirmed and extended with the use of a genetic model for VLC depletion, which demonstrated that short-term therapeutic depletion of VLCs alleviates immunosuppression and allows for efficacious vaccination against model tumor antigens in tumor-bearing mice. These studies provide a mechanistic explanation for how leukocytes contribute to ovarian tumor progression and, correspondingly, how leukocyte depletion inhibits tumor growth.

Influence of ambient atmosphere on charge transport in polycrystalline thin films of three simple aromatic hydrocarbons.

Drift mobility of charge carriers in p-terphenyl, p-quaterphenyl and tetracene polycrystalline thin films was measured using the classical time-of-flight method. The measurements were carried out both in the atmosphere and in vacuum of the order of 10( - 3) Torr. The mobility measured in the atmosphere is of the order of 10(-4)cm2 V(-1) s(-1) and turns out to be about 1 order of magnitude higher than that measured in vacuum. It is suggested that the hopping transport of charge dominates in the structures investigated. The increase in the mobility for the measurements in the atmosphere probably results from the additional localized states due to water and other atmosphere molecules.

Aging phenomena of chitosan and chitosan-diclofenac sodium system detected by low-frequency dielectric spectroscopy.

The use of natural polymers for design of dosage form has received considerable attention recently, especially from the safety point of view. Among these polymers, chitosan shows very interesting biological, chemical and physical properties which makes it possible to use chitosan for various pharmaceutical applications. Microcrystalline chitosan (MCCh) is a special multifunctional polymeric material existing in the form of either of gelatinous water dispersion or a powder. Thermal aging of chitosan and chitosan-diclofenac sodium mixture have been studied using low-frequency dielectric measurements. The aging was carried out by annealing in ambient atmosphere in the temperature range between 25 degrees C and 100 degrees C. The dielectric losses in the aged samples proved to decrease by about one order of magnitude. The additional measurements of molecular weight distribution and infrared absorption were also carried out for better understanding of nature of the ageing phenomena. Partial evacuation of water, cross-linking and improvement of structural order may be suggested to be a result of thermal aging of the investigated materials.

[The Saint syndrome]. / A Saint-szindróma.

In connection with two cases authors review our current body of knowledge on Saint's triad that means the concomitant occurrence of cholelithiasis, hiatus hernia and colonic diverticulosis. Though each component of this syndrome is fairly common, the Saint's triad is relatively seldom encountered. It does happen so because not all the components are likely to cause clinical symptoms. Consequently diagnosis and subsequent therapy are targeted at the dominating symptoms. On the other hand, the existence of the syndrome is also not sufficiently known in clinical practice. Authors stress that in the event of simultaneous symptoms suggestive of atypic cholelithiasis, colonic diverticulosis and hiatus hernia one has to consider a potential Saint's triad. Therefore it is recommended to verify or exclude each of the three components to establish a precise diagnosis and adequate subsequent therapy.