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Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. Genome-wide association studies (GWAS) have identified ~30 AUD risk genes in European populations, but many fewer in East Asians. We conducted GWAS and genome-wide meta-analysis of AUD in 13,551 subjects with East Asian ancestry, using published summary data and newly genotyped data from five cohorts: (1) electronic health record (EHR)-diagnosed AUD in the Million Veteran Program (MVP) sample; (2) DSM-IV diagnosed alcohol dependence (AD) in a Han Chinese–GSA (array) cohort; (3) AD in a Han Chinese–Cyto (array) cohort; and (4) two AD Thai cohorts. The MVP and Thai samples included newly genotyped subjects from ongoing recruitment. In total, 2254 cases and 11,297 controls were analyzed. An AUD polygenic risk score was analyzed in an independent sample with 4464 East Asians (Genetic Epidemiology Research in Adult Health and Aging (GERA)). Phenotypes from survey data and ICD-9-CM diagnoses were tested for association with the AUD PRS. Two risk loci were detected: the well-known functional variant rs1229984 in ADH1Band rs3782886 in BRAP(near the ALDH2gene locus) are the lead variants. AUD PRS was significantly associated with days per week of alcohol consumption (beta = 0.43, SE = 0.067, p= 2.47 × 10−10) and nominally associated with pack years of smoking (beta = 0.09, SE = 0.05, p= 4.52 × 10−2) and ever vs. never smoking (beta = 0.06, SE = 0.02, p= 1.14 × 10−2). This is the largest GWAS of AUD in East Asians to date. Building on previous findings, we were able to analyze pleiotropy, but did not identify any new risk regions, underscoring the importance of recruiting additional East Asian subjects for alcohol GWAS.

Panzer et al describe the development of B cell deficient Lewis rats using CRISPR technology, and used these mice to demonstrate the effect of B cell deficiency in allogeneic kidney transplantation. Supplemental digital content is available in the text.

Genome-wide association studies (GWASs) have been successful in identifying loci associated with osteoporosis and obesity. However, the findings explain only a small fraction of the total genetic variance.

This study evaluates the effect of balanced ultrafiltration, modified ultrafiltration, and balanced ultrafiltration with modified ultrafiltration on inflammatory mediators in children’s open-heart surgery. Eighty children with congenital heart disease were randomly divided into four groups: control group (C group); balanced ultrafiltration group (BUF group); modified ultrafiltration group (MUF group); and balanced ultrafiltration with modified ultrafiltration group (B+M group). Clinical data of these groups were similar. Tumor necrosis factor (TNF), interleukin-8(IL-8), and E-selectin were measured at the beginning of cardiopulmonary bypass (CPB), 30 min later, at the cessation of CPB, at the cessation of MUF (MUF group and B+M group), and 2 hours postoperatively. During CPB, the concentrations of TNF, IL-8, and E-selectin increased significantly in C and MUF groups and did not change significantly in BUF and B+M groups. In the period of MUF, TNF and IL-8 increased; whereas, Eselectin did not change. The study shows that ultrafiltration can filter out the inflammatory mediators, but only BUF can decrease the concentrations of them. Moreover, MUF only can concentrate blood. Combining both techniques has both effects, but the effect of BUF was offset by MUF.

Objective:Age at menarche (AAM) is determined by the overall duration of endocrine-tissue sex hormone exposure levels. Osteoporosis, the most common metabolic bone disease, is characterized primarily by reduced bone mineral density (BMD) and an increased risk of low trauma fractures. Bone was an endocrine organ regulating the synthesis and secretion of sex steroid hormones. The mutual dependence between bone and gonads underscore the importance of genetic approaches to identify novel pleiotropic genetic factors coregulating BMD and AAM. In this study, we performed a bivariate genome-wide association study (GWAS) to explore novel ethnic common loci and/or genes that may influence both AAM and BMD.Methods:We analyzed genotyping data available for 826 unrelated Chinese subjects using genome-wide human genotyping arrays. After quality control, a total of 702 413 single-nucleotide polymorphisms (SNPs) were tested for association using a bivariate linear regression model. The interesting SNPs were replicated in three independent cohorts including 1728 unrelated Caucasians, 709 African-Americans, and 408 Hispanic-Americans.Results:We found four SNPs (rs10817638, rs7851259, rs10982287, and rs4979427), located upstream of the ATP6V1G1gene, were bivariately associated with hip BMD-AAM (P= 4.90 × 10−7, P= 1.07 × 10−6, P= 1.28 × 10−5, and P= 5.42 × 10−5, respectively). These four SNPs were replicated in African-Americans, with corresponding values of P= 1.95 × 10−2, P= 3.18 × 10−2, P= 2.57 × 10−2, and P= 3.64 × 10−2, respectively. rs10817638 and rs10982287 were further replicated in Caucasians (P= 1.76 × 10−2and P= 9.42 × 10−3, respectively) and Hispanic-Americans (P= 8.37 × 10−3and P= 1.52 × 10−3, respectively). Meta-analyses yielded stronger association signals for rs10817638 and rs10982287 with combined values of P= 3.02 × 10−9and P= 3.49 × 10−9, respectively.Conclusions:Our study implicated ATP6V1G1as a novel pleiotropic gene underlying variation of both BMD and AAM. The findings enhance our knowledge of genetic associations between BMD and AAM and provide a rationale for subsequent functional studies of these implicated genes in the pathophysiology of diseases/traits, such as osteoporosis and AAM.

Low density polyethylene (LDPE) was modified by the addition of commercial fire retardants FR01 and aluminium hydroxide (ATH). ATH/FR01/LDPE composites were prepared by melt blending and extrusion in a twin-screw extruder. ATH was first modified by a silane coupling agent KH550 then added to LDPE. The flame retardancy, electrical property and thermal behavior of the LDPE composites were investigated by limiting oxygen index (LOI), volume resistivity and thermogravimetric analysis (TGA), respectively. The results indicated that the surface modification of ATH (M-ATH) could greatly improve the dispersibility and compatibility with LDPE matrix. The mechanical property tests showed good mechanical properties of composite, compared with unmodified one, tensile strength and elongation of M-ATH/LDPE were all improved, and the addition of FR01 improved the flame retardancy of ATH/LDPE remarkably. TGA results demonstrate that char yield of M-ATH/FR01/LDPE (30/15/70) reaches 27 wt% at 600 ℃ in Ar atmosphere.

Ion-beam-assisted deposition (IBAD) was investigated as a potential way to increase the fretting fatigue resistance of Ti-8Al-1Mo-1V alloy at elevated temperature. Three coating systems, hard TiN film with good toughness and soft Al film of low friction and Cu/Ni multilayer films with modulation period thickness of 20~600nm have been applied on the base material. Coefficients of friction and fretting fatigue lives of the specimens with and without film were compared. The film damage was characterized through scanning electron microscopy. The results indicate that the IBAD technique can prepare all films with high bonding strength and excellent lubricating properties. The fretting fatigue life of the Ti-8Al-1Mo-1V alloy with the TiN film was improved by a factor of 2.4 as compared to the uncoated substrate at elevated temperature because of the excellent wear and fatigue resistance and good toughness of the film. Excellent wear resistance and good anti-fatigue properties could be simultaneously obtained by a single hard film to control the fretting fatigue damage. The IBAD Al film significantly improved the fretting fatigue resistance of the Ti-8Al-1Mo-1V alloy at elevated temperature for good lubricating property. The fretting fatigue resistance of the Ti-8Al-1Mo-1V alloy was improved by all the Cu/Ni multilayer films. However, the fretting fatigue resistance did not increase monotonically with the modulation period of the films. Films with a modulation period of 200 nm had the highest fretting fatigue resistance among the multilayer films prepared owing to their high toughness and strength and good lubricating and anti-fatigue action. The fretting fatigue resistance of films with a modulation period of 20 nm was low because of the poor fracture toughness and crack propagation resistance, even though these films had the highest hardness and good fretting wear resistance. Thus, comprehensive properties, including high toughness and strength, must be considered for multilayer films used to improve the fretting fatigue resistance of titanium alloys.

Polyoxymethylene (POM) composites filled with low-density polyethylene (LDPE) and wood fibers were prepared by injection-molding. Friction and wear tests were carried out in a reciprocating sliding tribotester. Results showed that 5wt.%LDPE acted effectively as the internal lubricant for POM. Further addition of the wood fiber increased the wear rate of the POM/LDPE composites but had little effect on the coefficient of coefficient in the presence of LDPE. SEM observations showed that the main wear mechanism for unfilled POM was adhesive wear, while in the case of POM composites abrasion and fatigue seemed to govern the wear process. It was suggested that, the POM/LDPE/Wood fiber composite, which is low-cost and environmentally friendly, has the potential for tribological applications.

Polyoxymethylene (POM) composites filled with low-density polyethylene (LDPE) and sisal fibers (SF) were prepared by extrusion and injection molding. Sisal fibers were treated by various concentrations of NaOH solution to improve the poor compatibility between SF and matrix. Fourier transform infrared spectroscopy (FTIR) analysis and scanning electron microscope (SEM) test were used to confirm the surface treatment. The effects of SF alkaline treatment on the mechanical and tribological properties of POM composites were determined by using tensile test, impact test and friction and wear test. The worn surfaces of composites were investigated by SEM. Results showed that the composite filled with 12.5% NaOH treated SF exhibited the optimal mechanical and tribological properties among the all composites. The major wear mechanism of the composites was adhesive wear and abrasive grain wear.

Bone size is an important risk factor of osteoporotic fractures and has strong genetic determination. However, genetic studies on bone size variation are relatively rare. In the present study, we conducted a linkage exclusion mapping for bone size variation on chromosomes 1, 4, 6, and 17 in 79 Caucasian pedigrees. For hip bone size variation, several genomic regions were excluded at effect sizes of 10% or greater, including regions of 61–77cM at 1p35-p34, 43–59cM at 4p15-p13, 1–59cM at 6p25-p21, 82–88cM at 17q23-q24, and 113–114cM at 17q25. For spine bone size, at effect sizes of 10% or greater, we excluded regions of 115–122cM at 1p31-p22, 136–141cM at 1p21, 207–260cM at 1q31-q42, 20–89cM at 4p16-q21, 11–21cM at 6p24-p23, and 1–6cM at 17p13. These results suggested that a number of candidate genes located in the excluded regions, such as the growth hormone (GH) gene, tumor necrosis factor-alpha (TNF-α) gene, and bone morphogenetic protein-3 (BMP3) gene, are unlikely to have a substantial effect on bone size variation in this Caucasian population.

Objectives: To determine the heritability of BMI and to examine the mode of inheritance of BMI variation in Chinese. Research Methods and Procedures: Familial correlation and complex segregation analyses for BMI were undertaken in a Chinese sample composed of 392 nuclear families, with 1190 total individuals. Results: A moderate heritability was found for BMI (h2= 0.419‐0.492). The obtained results do not support a major gene for BMI in our samples. BMI may be inherited in a complex and non‐Mendelian manner in Chinese. Discussion: The findings of this study suggest that identification of specific genes for BMI in Chinese, at least within the same data set, is a serious challenge because of the lack of evidence of a major gene for BMI in our Chinese sample.

Abstract.:  Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the −174G/C promoter polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the T → C polymorphism in intron 5 of the transforming growth factor β1 (TGF-β1) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms of these five markers with other populations using the χ2 test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were identified. For the −174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A 1 at the Sp1, Asn363Ser, and T → C marker sites that have been found to be polymorphic in other populations were not found in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms (P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers in osteoporosis genetic research in other populations.

Of 5587 operations for congenital heart disease that we performed between January 1976 and December 1993, 2085 were for correction of ventricular septal defects. Paramembranous, muscular, and atrioventricular canal types were repaired through a right atrial incision, whereas subpulmonary and conus type defects were repaired through a pulmonary artery incision. Circulatory arrest under deep hypothermia was used for patients under 2 years of age or with body weight of less than 10 kg. There were 48 postoperative deaths. The overall mortality was 2.3% and it was related to the age and weight of the patients. The age at which surgical repair was undertaken depended on the position and size of the defect and the degree of intracardiac shunt. Patients with associated pulmonary hypertension underwent surgery before 2 years of age. Early repair of subpulmonary ventricular defects is recommended to prevent aortic insufficiency resulting from valve prolapse. The keys to successful repair were avoidance of a right ventricular incision, improvement of right ventricular function, and postoperative management of pulmonary hypertension. The operative mortality was reduced from 10.14% in the 1970s to 6.43% in the early 1980s by improvements in surgical procedure and postoperative management with a further reduction to 1.25% in recent years, which we attribute partly to the use of a hollow fiber membrane oxygenator.

Dual-parameter correlation analysis of the redox potential data of five aromatic compounds shows that the transition states of the polarographic processes are affected by the spin-delocalization effect in addition to the polar effect of the substituents.

The relative rates of the addition of trichloromethyl radicals to styrene, α,β,β-trifluorostyrene and phenylacetylene in cyclohexane at 65 °C, measured by a direct competition procedure, are 1:0.23:0.40.