Fetuin A concentration in the second trimester amniotic fluid of fetuses with Trisomy 21 appears to be lower: phenotypic considerations

Objective: We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. Methods. 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: The median concentration of fetuin A in amniotic fluid of trisomy 21 pregnancies (5.3 ng/ml) was statistically significantly lower (P value = 0.008) compared with that in euploid pregnancies (6.8 ng/mL). Conclusion: Lower levels of fetuin A in trisomy 21 may indicate an association with altered metabolic pathways in this early stage that could potentially be associated with features of the syndrome, such as growth restriction or impaired osteogenesi

MINERALOGY AND ORGANIC MATTER CONTENT OF BOTTOM ASH SAMPLES FROM AGIOS DIMITRIOS POWER PLANT, GREECE

Four bottom ash samples from the Power Units of the Agios Dimitrios Power Plant were studied by the method of PXRD to determine their semi-quantitative mineralogical composition. Their organic matter content was calculated by a wet chemical process. Also, the loss on ignition was measured. The samples are constituted mainly of calcite, quartz and feldspars, while micas, clays, gehlenite and portlandite were determined in a few samples in smaller quantities. The amorphous material varied between 10-43 wt. %, while organic matter varied between 5-42 wt. %. Measurements of the loss on ignition overestimate the unburned lignite contents in the bottom ash samples. The management of bottom ashes with high contents of unburned lignite should differ to that of the fly ashes. The oxidation of the inorganic compounds of the unburned lignite may lead to environmental degradation of the landfill areas. Samples showing lower values of organic matter are suitable for a series of uses, such as: snow and ice control, as an aggregate in lightweight concrete masonry units,as a raw feed material for portland cement, as an aggregate in cold mix emulsified asphalt mixes, base or sub-base courses, or in shoulder construction. Systematic study of the unburned lignite of bottom ashes is needed for possible re-combustion

THE CATION EXCHANGE CAPACITY OF INDUSTRIAL MINERALS AND ROCKS OF MILOS ISLAND

Τέσσερα δείγματα μπεντονίτη, δύο περλίτη, ένα καολίνη και ένα κίσσηρης από πέντε ορυχεία της Νήσου Μήλου, μελετήθηκαν ως προς την ιοντοανταλλακτική τους ικανότητα (ΙΑΙ) και την ορυκτολογική τους σύσταση (% κ.β.) με τις μεθόδους του κορεσμού σε οξικό αμμώνιο και της περιθλασιμετρίας ακτίνων-Χ, αντίστοιχα. Τα δείγματα του μπεντονίτη περιέχουν 68-100% κ.β. αργιλικά ορυκτά και παρουσιάζουν ΙΑΙ 35-121 meq/lOOg, ενώ το δείγμα του καολίνη περιέχει 41% κ.β. αργιλικά ορυκτά και παρουσιάζει ΙΑΙ 28 meq/lOOg. Τα άμορφα υλικά αποτελούν το κύριο συστατικό των δειγμάτων του περλίτη (73-77% κ.β.) και του δείγματος της κίσσηρης (88% κ.β.).Οι τιμές της ΙΑΙ των περλιτών είναι 3-4 meq/lOOg, ενώ του δείγματος της κίσσηρης 73 meq/lOOg. Η ΙΑΙ των δειγμάτων εμφανίζει θετική συσχέτιση με τις περιεκτικότητες του συνόλου των μικρο-πορώδων ορυκτών (αργιλικά ορυκτά+μαρμαρυγίες), καθώς και με το σύνολο μικρο-πορώδων ορυκτών ^άμορφα υλικά, επηρεαζόμενη κυρίως από το ποσοστό των αργιλικών ορυκτών.Four samples of bentonite, two of perlite, a kaolin and a pumice sample from five mines of Milos Island, have been investigated for their Cation Exchange Capacity (CEC) and the mineralogical composition (wt.%), by using the Ammonium Acetate Saturation (AMAS) method and X-Ray Powder Diffraction (XRPD) method, respectively. The bentonite samples contain 68-100 wt.% clay minerals and show CEC values of 35-121 meq/100g, while the kaolin sample contain 41 wt.% clay minerals and show CEC value of 28 meq/100g. The amorphous materials are the main constituent of the perlite samples (73-77 wt.%) and pumice sample (88 wt.%). The CEC values ofperlites were 3-4 meq/100g, while the pumice sample showed a CEC value of 73 meq/100g. The CEC of the samples showed positive correlations with the total content of microporous minerals (clay minerals+micas) as well as with the microporous minerals+amorphous content, mainly affected by the clay minerals content

Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing

Background: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. Methods: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium(TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. Results: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. Conclusions: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.Peer reviewe

HUMAN4D: A human-centric multimodal dataset for motions and immersive media

We introduce HUMAN4D, a large and multimodal 4D dataset that contains a variety of human activities simultaneously captured by a professional marker-based MoCap, a volumetric capture and an audio recording system. By capturing 2 female and 2 male professional actors performing vari

Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P <7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.Peer reviewe

ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk

PURPOSE: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). EXPERIMENTAL DESIGN: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. RESULTS: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)-like (N = 226). We then examined their association with breast cancer risk in the case-control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35-3.41), 1.57 (95% CI, 1.41-1.75), and 1.19 (95% CI, 1.08-1.31), respectively. The meta-analysis of population-specific datasets showed similar results. CONCLUSIONS: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland