Monotone integrated large eddy simulations for supersonic boundary layer flows

Monotone integrated large eddy simulation (MILES) has been carried out to simulate supersonic turbulent boundary layer flows for relatively high Reynolds numbers. Two Riemann solver based methods, Osher’s and Roe’s schemes, were tested along with a MUSCL scheme to investigate their suitability for MILES simulation. The effects of different limiters used in the MUSCL scheme were also tested regarding the MILES simulations

Variable Modal Parameter Identification for Non-Linear Mdof Systems. Part II: Experimental Validation and Advanced Case Study

The purpose of Part II is to provide an experimental validation of the methodology presented in Part I and to consider a representative engineering case, the study of which requires a relatively large numerical model. A beam system with cubic stiffness type non-linearity was used in the experimental study. The non-linear response was measured at three locations and the underlying linear system was obtained via linear modal analysis of low-excitation response data. The non-linear parameter variations were obtained as a function of the modal amplitude and the response of the system was generated for other force levels. The results were found to agree very well with the corresponding measurements, indicating the success of the non-linear modal analysis methodology, even in the presence of true experimental noise. An advanced numerical case study that included both inherent structural damping and non-linear friction damping, was considered next. The linear finite element model of a high-pressure turbine blade was used in conjunction with three local non-linear friction damper elements. It was shown that the response of the system could be predicted at any force level, provided that that non-linear modal parameters were available at some reference force level. The predicted response levels were compared against those obtained from reference simulations and very good agreement was achieved in all cases

The Role of Translation Initiation Regulation in Haematopoiesis

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control

Ethnic differences translate to inadequacy of high-risk screening for gestational diabetes mellitus in an Asian population: a cohort study

Background: universal and high-risk screening for gestational diabetes mellitus (GDM) has been widely studied and debated. Few studies have assessed GDM screening in Asian populations and even fewer have compared Asian ethnic groups in a single multi-ethnic population.Methods: 1136 pregnant women (56.7% Chinese, 25.5% Malay and 17.8% Indian) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were screened for GDM by 75-g oral glucose tolerance test (OGTT) at 26–28 weeks of gestation. GDM was defined using the World Health Organization (WHO) criteria. High-risk screening is based on the guidelines of the UK National Institute for Health and Clinical Excellence.Results: universal screening detected significantly more cases than high-risk screening [crude OR 2.2 (95% CI 1.7-2.8)], particularly for Chinese women [crude OR = 3.5 (95% CI 2.5-5.0)]. Pre-pregnancy BMI > 30 kg/m2 (adjusted OR = 3.4, 95% CI 1.5-7.9) and previous GDM history (adjusted OR = 6.6, 95% CI 1.2-37.3) were associated with increased risk of GDM in Malay women while GDM history was the only significant risk factor for GDM in Chinese women (adjusted OR = 4.7, 95% CI 2.0-11.0).Conclusion: risk factors used in high-risk screening do not sufficiently predict GDM risk and failed to detect half the GDM cases in Asian women. Asian women, particularly Chinese, should be screened to avoid under-diagnosis of GDM and thereby optimize maternal and fetal outcome

Charmless hadronic decays B→PP,PV,VVB \to PP, PV, VV and new physics effects in the general two-Higgs doublet models

Based on the low-energy effective Hamiltonian with the generalized factorization, we calculate the new physics contributions to the branching ratios of the two-body charmless hadronic decays of $B_u$ and $B_d$ mesons induced by the new gluonic and electroweak charged-Higgs penguin diagrams in the general two-Higgs doublet models (models I, II and III). Within the considered parameter space, we find that: (a) the new physics effects from new gluonic penguin diagrams strongly dominate over those from the new $\gamma$- and $Z^0$- penguin diagrams; (b) in models I and II, new physics contributions to most studied B meson decay channels are rather small in size: from -15% to 20%; (c) in model III, however, the new physics enhancements to the penguin-dominated decay modes can be significant, $\sim (30 -200)$, and therefore are measurable in forthcoming high precision B experiments; (d) the new physics enhancements to ratios {\cal B}(B \to K \etap) are significant in model III, $\sim (35 -70)$, and hence provide a simple and plausible new physics interpretation for the observed unexpectedly large B \to K \etap decay rates; (e) the theoretical predictions for ${\cal B}(B \to K^+ \pi)$ and ${\cal B}(B \to K^0 \pi^+)$ in model III are still consistent with the data within $2\sigma$ errors; (f) the significant new physics enhancements to the branching ratios of $B \to K^0 \pi^0, K^* \eta, K^{*+} \pi^-, K^+ \phi, K^{*0} \omega, K^{*+} \phi$ and $K^{*0} \phi$ decays are helpful to improve the agreement between the data and the theoretical predictions; (g) the theoretical predictions of ${\cal B}(B \to PP, PV, VV)$ in the 2HDM's are generally consistent with experimental measurements and upper limits ($90$)Comment: 55 pages, Latex file, 17 PS and EPS figures. With minor corrections, final version to be published in Phys.Rev. D. Repot-no: PKU-TH-2000-4

Charm multiplicity and the branching ratios of inclusive charmless b quark decays in the general two-Higgs-doublet models

In the framework of general two-Higgs-doublet models, we calculate the branching ratios of various inclusive charmless b decays by using the low energy effective Hamiltonian including next-to-leading order QCD corrections, and examine the current status and the new physics effects on the determination of the charm multiplicity $n_c$ and semileptonic branching ratio $B_{SL}$. Within the considered parameter space, the enhancement to the ratio $BR(b \to s g)$ due to the charged-Higgs penguins can be as large as a factor of 8 (3) in the model III (II), while the ratio $BR(b \to no charm)$ can be increased from the standard model prediction of 2.49% to 4.91% (2.99%) in the model III (II). Consequently, the value of $B_{SL}$ and $n_c$ can be decreased simultaneously in the model III. The central value of $B_{SL}$ will be lowered slightly by about 0.003, but the ratio $n_c$ can be reduced significantly from the theoretical prediction of $n_c= 1.28 \pm 0.05$ in the SM to $n_c= 1.23 \pm 0.05$, $1.18 \pm 0.05$ for $m_{H^+}=200, 100$ GeV, respectively. We find that the predicted $n_c$ and the measured $n_c$ now agree within roughly one standard deviation after taking into account the effects of gluonic charged Higgs penguins in the model III with a relatively light charged Higgs boson.Comment: 25 pages, Latex file, axodraw.sty, 6 figures. Final version to be published in Phys.Rev.

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions

Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation:This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population