Recurrent triploidy due to a failure to complete maternal meiosis II: whole-exome sequencing reveals candidate variants

Triploidy is a relatively common cause of miscarriage; however, recurrent triploidy has rarely been reported. A healthy 34-year-old woman was ascertained because of 18 consecutive miscarriages with triploidy found in all 5 karyotyped losses. Molecular results in a sixth loss were also consistent with triploidy. Genotyping of markers near the centromere on multiple chromosomes suggested that all six triploid conceptuses occurred as a result of failure to complete meiosis II (MII). The proband's mother had also experienced recurrent miscarriage, with a total of 18 miscarriages. Based on the hypothesis that an inherited autosomal-dominant maternal predisposition would explain the phenotype, whole-exome sequencing of the proband and her parents was undertaken to identify potential candidate variants. After filtering for quality and rarity, potentially damaging variants shared between the proband and her mother were identified in 47 genes. Variants in genes coding for proteins implicated in oocyte maturation, oocyte activation or polar body extrusion were then prioritized. Eight of the most promising candidate variants were confirmed by Sanger sequencing. These included a novel change in the PLCD4 gene, and a rare variant in the OSBPL5 gene, which have been implicated in oocyte activation upon fertilization and completion of MII. Several variants in genes coding proteins playing a role in oocyte maturation and early embryonic development were also identified. The genes identified may be candidates for the study in other women experiencing recurrent triploidy or recurrent IVF failur

Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling study of screening performance.

Background: Prenatal cystic fibrosis (CF) screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Conclusions: Compared with current screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.The author(s) declared that no grants were involved in supporting this work

Изучение гранулометрического состава порошков стандартных образцов природных сред

One of the most important stages of the developing certified reference materials (CRM) of solid natural samples is to describe a particle size distribution of prepared powders. The particle size distribution affects the degree of material homogeneity and the value representative of the analytical sample mass. The collection of CRMs was being produced at the Vinogradov Institute of Geochemistry SB RAS through a long time span; therefore the grain-size compositions of the CRM powders were measured by different instrumental methods and assessed at different scales. The laser diffraction analyzer HELOS/BR was employed to accurately and rapidly measure the grain-size composition of CRM natural sample powders. New measurements confirm that the particle size distribution of CRMs of magmatic and metamorphic rocks and sediments of Lake Baikal developed 45 and 25 years ago, accordingly have not changed fundamentally. The multimodal distributions ofparticle sizes of investigated CRMs clearly reflect the differences in mineral and chemical compositions. Aggregating of the particles of different composition and origin during long-term storage of powders is not observed. The measurement results of particle size compositions of the CRM powders show a slight dependence on the weight put into the device, as well as its mineral composition. The homogeneity of the substance of studied standard samples was confirmed by low quantities of representative sub-samples (0.075-0.100 g) for a wide range of elements determined by modern instrumental analytical methods. The use of laser diffraction analyzers type HELOS could help to certify the particle size composition of CRM powder as repeatable metrological characteristic.При разработке стандартных образцов (СО) состава твердых природных сред требуется оценивать гранулометрический состав приготовленных порошков, так как эта характеристика влияет на степень однородности материала СО и величину представительной массы аналитической навески. Коллекция стандартных образцов ИГХ СО РАН природных сред создавалась в течение длительного периода времени, поэтому приведенные в паспортах распределения частиц по размерам были измерены различными способами и приборами и оценены в различных шкалах. Для точного и экспрессного измерения гранулометрических составов порошков стандартных образцов состава природных сред использован лазерный дифракционный анализатор HELOS. Выполнены новые измерения гранулометрических составов пяти СО магматических и трех СО метаморфических горных пород, а также двух СО донных осадков озера Байкал. Обнаружена слабая зависимость результатов измерения гранулометрического состава от массы порошка, вводимой в прибор, и минерального состава СО. Сравнение полученных распределений с данными, приведенными в паспортах, показало отсутствие принципиальных изменений гранулометрического состава за время, прошедшее со времени изготовления стандартных образцов. Многомодальные распределения частиц по размерам наглядно отражают различия в минеральном и химическом составе исследованных СО. Однородность вещества изученных стандартных образцов подтверждена малыми величинами представительных навесок (0.075-0.100 г) для широкого круга элементов, определяемых современными инструментальными аналитическими методами. Использование лазерных дифракционных анализаторов типа HELOS позволит аттестовать гранулометрический состав порошкового стандартного образца как повторяемую во времени метрологическую характеристику

Realization of the Model as a Condition of Forming Readiness to Work with Orphans and Children Without Parental Care

У статті аргументовано необхідність моделювання педагогічного процесу, проаналізовано методологічні підходи, на яких базується розробка моделі. Представлена модель процесу підготовки майбутніх соціальних педагогів до роботи з дітьми-сиротами та дітьми, позбавленими батьківського піклування, визначено зміст блоків з позиції їх функціонування. У межах аналізу змістовно-технологічного блоку моделі підготовки майбутніх соціальних педагогів схарактеризовано авторський спецкурс «Соціально-педагогічна робота з дітьми-сиротами та дітьми, позбавленими батьківського піклування».The article proves the need to form a model of a pedagogical process, analyses the methodological approaches which are the base of the model. It is given the model of the process how to prepare the future social teachers to work with orphans and children without parental care, as well as it is defined the context of the model parts from the point of their functions. In the frames of analyses of content-technological block of the model of future social teacher training the author’s special course «Social-pedagogical work with orphans and children without parental care» is characterized

Supplementary Material for: Cell-Free Placental DNA in Maternal Plasma in Relation to Placental Health and Function

<i>Background:</i> While cell-free placental DNA (cfp-DNA) increases in response to certain pathological conditions, confounding variables, such as placental size, may also contribute to its release. Furthermore, the relationship between cfp-DNA and maternal serum proteins has not been well investigated. <i>Objective:</i> To analyze plasma cfp-DNA levels and correlate with measurable placental parameters, maternal serum proteins, or pathologic conditions reflecting placental dysfunction. <i>Method:</i>Methylated fraction of <i>RASSF1A</i> was quantified in maternal plasma as a measure of cfp-DNA in a cohort of 86 pregnant women. <i>Results:</i> Placental dimensions or weight had no impact on cfp-DNA levels in noncomplicated pregnancies (n = 63). However, an association between β-hCG and cfp-DNA levels (p = 0.0012) was detected. Complications occurred in 23 pregnancies including chromosomal abnormalities, gestational hypertension, intrauterine growth restriction, and preterm birth. There was overall a skewed distribution (<-1 SD or >1 SD from mean) for cfp-DNA in the abnormal group, although due to the small number of samples for each pathology, we provide only descriptive data to assess possible trends in cfp-DNA variation.<i>Conclusion:</i> While cfp-DNA levels outside of the normal range may reflect placental distress, this relationship may be masked by a number of physiological confounders. The independence of cfp-DNA from β-hCG levels commonly assessed in pregnancy need to be further addressed

Assessing extent-of-equivalence of Chinese and Russian certified reference materials of plants using data of mass spectrometry with inductively coupled plasma

A method for studying the adequacy of CRM's compositions ofplants using aggregative assessment based on exploratory data analysis was proposed. It combines for each analyte such statistical estimates as adequacy of calibrations (Fischer's criterion) and quality of results of the analysis (relative bias - RB). The value of RB should not exceed ±10 % (professional criteria). This method clearly and compactly reflects the adequacy (or inadequacy) of the investigated CRM's compositions. The extent-of-equivalence of the compositions of the Chinese and Russian CRMs on data of mass spectrometry with inductively coupled plasma (MS-ICP) were confirmed by the aggregative assessments

Analysis of vegetable oils by high-performance liquid chromatography

yesA reversed-phase high-performance liquid chromatographic procedure is proposed to monitor the fatty-acid and triglyceride composition of sunflower-seed oil. The procedure uses a column packed with Diasfer- 110-C18 (6 mm), a 2 : 8 mixture of acetonitrile and acetone as an eluent, and refractometric detection. Analyses that use simple normalization and normalization with correction factors that take into account the difference between calculated refraction coefficients of different triglycerides are comparedBelgorod State Universit

Analysis of vegetable oils by high-performance liquid chromatography

A reversed-phase high-performance liquid chromatographic procedure is proposed to monitor the fatty-acid and triglyceride composition of sunflower-seed oil. The procedure uses a column packed with Diasfer- 110-C18 (6 mm), a 2 : 8 mixture of acetonitrile and acetone as an eluent, and refractometric detection. Analyses that use simple normalization and normalization with correction factors that take into account the difference between calculated refraction coefficients of different triglycerides are comparedyesBelgorod State Universit

Study of particle size distribution of environment certified reference material

One of the most important stages of the developing certified reference materials (CRM) of solid natural samples is to describe a particle size distribution of prepared powders. The particle size distribution affects the degree of material homogeneity and the value representative of the analytical sample mass. The collection of CRMs was being produced at the Vinogradov Institute of Geochemistry SB RAS through a long time span; therefore the grain-size compositions of the CRM powders were measured by different instrumental methods and assessed at different scales. The laser diffraction analyzer HELOS/BR was employed to accurately and rapidly measure the grain-size composition of CRM natural sample powders. New measurements confirm that the particle size distribution of CRMs of magmatic and metamorphic rocks and sediments of Lake Baikal developed 45 and 25 years ago, accordingly have not changed fundamentally. The multimodal distributions ofparticle sizes of investigated CRMs clearly reflect the differences in mineral and chemical compositions. Aggregating of the particles of different composition and origin during long-term storage of powders is not observed. The measurement results of particle size compositions of the CRM powders show a slight dependence on the weight put into the device, as well as its mineral composition. The homogeneity of the substance of studied standard samples was confirmed by low quantities of representative sub-samples (0.075-0.100 g) for a wide range of elements determined by modern instrumental analytical methods. The use of laser diffraction analyzers type HELOS could help to certify the particle size composition of CRM powder as repeatable metrological characteristic

Оценивание согласованности китайских и российских стандартных образцов растений по данным масс-спектрометрии с индуктивно связанной плазмой

A method for studying the adequacy of CRM's compositions ofplants using aggregative assessment based on exploratory data analysis was proposed. It combines for each analyte such statistical estimates as adequacy of calibrations (Fischer's criterion) and quality of results of the analysis (relative bias - RB). The value of RB should not exceed ±10 % (professional criteria). This method clearly and compactly reflects the adequacy (or inadequacy) of the investigated CRM's compositions. The extent-of-equivalence of the compositions of the Chinese and Russian CRMs on data of mass spectrometry with inductively coupled plasma (MS-ICP) were confirmed by the aggregative assessments.Предложен способ изучения согласованности составов стандартных образцов (СО) растений с помощью обобщенной оценки, сформированной на основе разведочного анализа данных. В ней для каждого аналита используются такие статистические оценки, как адекватность градуировок (критерий Фишера) и качество результатов анализа (относительная систематическая погрешность - ОСП). При этом величина ОСП не должна превышать ±10 % отн. (профессиональный критерий). Способ наглядно и компактно отражает адекватность или неадекватность исследуемых составов СО. По данным масс-спектрометрии с индуктивно связанной плазмой (МС-ИСП) с помощью предложенной обобщенной оценки подтверждена адекватность составов четырех китайских и трех российских СО