To assess the statistical significance of associations between variants and traits, genome-wide association studies (GWAS) should employ an appropriate threshold that accounts for the massive burden ...of multiple testing in the study. Although most studies in the current literature commonly set a genome-wide significance threshold at the level of P=5.0 × 10
, the adequacy of this value for respective populations has not been fully investigated. To empirically estimate thresholds for different ancestral populations, we conducted GWAS simulations using the 1000 Genomes Phase 3 data set for Africans (AFR), Europeans (EUR), Admixed Americans (AMR), East Asians (EAS) and South Asians (SAS). The estimated empirical genome-wide significance thresholds were P
=3.24 × 10
(AFR), 9.26 × 10
(EUR), 1.83 × 10
(AMR), 1.61 × 10
(EAS) and 9.46 × 10
(SAS). We additionally conducted trans-ethnic meta-analyses across all populations (ALL) and all populations except for AFR (ΔAFR), which yielded P
=3.25 × 10
(ALL) and 4.20 × 10
(ΔAFR). Our results indicate that the current threshold (P=5.0 × 10
) is overly stringent for all ancestral populations except for Africans; however, we should employ a more stringent threshold when conducting a meta-analysis, regardless of the presence of African samples.
Background Atrial fibrillation (AF) is the most common sustained arrhythmia, and it causes a high rate of complications such as stroke. It is known that AF begins as paroxysmal form and gradually ...progresses to persistent form, and sometimes it is difficult to identify paroxysmal AF (PAF) before having stroke. The aim of this study is to evaluate the risk of PAF and stroke using genetic analysis and circulating biomarkers. Materials and methods A total of 600 adult subjects were enrolled (300 from PAF and control groups). Peripheral blood was drawn to identify the genetic variation and biomarkers. Ten single nucleotide polymorphisms (SNPs) were analyzed, and circulating cell-free DNA (cfDNA) was measured from plasma. Four microRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were quantified in serum using quantitative RT-PCR. Results Genotyping identified 4 single nucleotide polymorphisms (SNPs) that were significantly associated with AF (rs6817105, rs3807989, rs10824026, and rs2106261), and the genetic risk score using 4 SNPs showed the area under the curve (AUC) of 0.631. Circulating miRNAs and cfDNA did not show significant differences between PAF and control groups. The concentration of cfDNA was significantly higher in patients with a history of stroke, and the AUC was 0.950 to estimate the association with stroke. Conclusion The risk of AF could be assessed by genetic risk score. Furthermore, the risk of stroke might be evaluated by plasma cfDNA level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The estimation of interaction parameters in liquid iron is strongly demanded due to the difficulty of their measurements and its time consuming for enormous combinations of target solute elements in ...liquid iron. Therefore, several estimation models have been developed so far. In this study, the interaction parameters between metal elements and/or metalloid elements in liquid Fe are estimated by neural network computation in order to improve the estimation accuracy. The input parameters used in the neural network computation are assessed by lateral inhibition learning. The estimation results by nerural network computation with the assessed parameters reasonably agree with the recommended values in the literature.
Expansion of the system for thermodynamic parameters in liquid iron is expected for the improvement in iron & steelmaking processes. The development of their calculation method is one of the issues ...for its realization. In the present work, we proposed a calculation method for an activity coefficient of solute in infinite dilute liquid iron to element i, γοi, based on the surface tension of binary liquid Fe alloys. It was found that the estimated values by our proposed method agree with recommended literature data.
Background: Mumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is highly variable. ...Nationwide studies in Japan with a large age range are lacking.Methods: This was a retrospective observational investigation of the 2005–2017 mumps burden using employment-based health insurance claims data. Data were analyzed for 5,190,326 people aged 0–64 years to estimate the incidence of mumps deafness.Results: Of 68,112 patients with mumps (36,423 males; 31,689 females), 102 (48 males; 54 females) developed mumps deafness—an incidence of 15.0 per 10,000 patients (1 in 668 patients). Fifty-four (52.9%) patients had mumps deafness in childhood (0–15 years), and 48 (47.1%) had mumps deafness in adolescence and adulthood (16–64 years); most cases occurred in childhood, the peak period for mumps onset. The incidence of mumps deafness per 10,000 patients was 73.6 in adolescence and adulthood, 8.4 times higher than the incidence of 8.8 in childhood (P < 0.001). In childhood, the incidence of mumps deafness was 7.2 times higher among 6–15-year-olds (13.8; 95% CI, 10.2–18.2) than among 0–5-year-olds (1.9; 95% CI, 0.6–4.5), and this difference was statistically significant (P < 0.001). No sex difference was observed.Conclusions: The incidence of mumps deafness per 10,000 patients aged 0–64 years was 15.0 (1 in 668 patients). A secondary risk of deafness following mumps virus infection was identified not only for children, but also for adolescents and adults.
A zirconia oxygen sensor is an electrochemical device for rapidly measuring oxygen concentrations in molten metals at high temperatures. It is desirable to make the sensors capable of continuous, ...long-time measurements. Here, the effect on the electromotive force of a partial equilibrium state on the surface of a zirconia solid electrolyte in a zirconia oxygen sensor was investigated to reveal the factors preventing long-time measurements. The reference electrode was a mixture of W and WO2. Continuous measurements were performed in molten iron containing carbon for deoxidization. The electromotive force between the positive reference electrode and the negative sample electrode of the sensor decreased from a positive value to zero over time. This was because a metallic tungsten layer formed on the surface of the zirconia electrolyte by the reduction of the tungsten oxide via oxygen diffusion through the zirconia tube. In addition, the equilibrium in the reference electrode was disturbed during the measurements. A direct electrical current was applied to the sensor to examine the relationship between the surface and measured values. The electromotive force during the current was maintained at a higher value than that without the current because of induced re-oxidation at the zirconia surface. However, a long-time application could cause over-oxidation and dissolution of the reference electrode surface.
A neural network model was developed in this paper to predict the contact angles of 21 metals and 14 solid oxides. 15 factors were used in the neural network model to distinguish different metal and ...oxide categories and experimental conditions. With 1120 contact angle values as the learning data, the neural network model was successfully developed. It can properly reproduce the experimental data on contact angles of molten metals and solid oxides under various conditions. Specifically, only three predictions among the total 1155 predictions were over 20% deviation from the experimental data. All the predictions on the 35 test data are within 20% deviation from the experimental values. Factors such as oxygen partial pressure and surface tension of molten metal were found to be important for a good model prediction. With the developed model, contact angle values of Fe and CeO2 were predicted.
Background: Mumps vaccination coverage is low in Japan, partly because of its voluntary nature. Although pediatric cases of mumps virus infection are captured by the National Epidemiological ...Surveillance of Infectious Diseases program under the Infectious Disease Law, there are currently no data regarding the occurrence of mumps and its complications in adults.Methods: We investigated the annual incidence rates of mumps and its complications based on health insurance reimbursement data for 5,209,660 individuals aged 0–64 years for 2005–2017, obtained from JMDC Inc., to estimate the mumps-related disease burden during this period.Results: There were three mumps outbreaks (2006, 2010, and 2016) during 2005–2017. The annual incidence of mumps was highest in individuals aged 0–5 years (808–3,792 per 100,000 persons), followed by those aged 6–15 years (658–2,141 per 100,000 persons). The incidence of mumps was higher in females than in males (male/female ratio, 0.90). Among mumps-related complications, the overall incidence (per 1,000 mumps cases) was highest for orchitis (6.6), followed by meningitis (5.8), deafness (1.3), pancreatitis (0.5), and encephalitis (0.3). No cases of oophoritis were noted. The overall incidence of mumps-related complications was 2.5 times higher in males than in females.Conclusions: This study revealed the disease burden due to mumps and its complications in Japan during 2005–2017. These data suggest the need for mumps-prevention measures in adolescents and adults, as well as in children.
PDF
