Determination of sibship in any two persons

BACKGROUND: Parentage testing laboratories may be asked to provide genetic evidence that two persons are or are not related, when no other relatives are available for study. Simple methods using autosomal, codominant, unlinked genetic systems can determine if two people are blood relatives (e.g., siblings). STUDY DESIGN AND METHODS: The odds ratios (full sibship index) of true sibling pairs were determined from two-child paternity cases and compared with regionally and racially matched control pairs of unrelated children. The sharing of two, one, or no alleles was observed in pairs of children at three independent, polymorphic VNTR (variable number of tandem repeat) sequences loci. The sibship index was calculated as (the chance that an observation would occur if two children were siblings) divided by (the chance that it would occur if the two were unrelated). Sibship indices and the frequencies of shared alleles were determined for 20 sibling pairs and 20 control pairs. RESULTS: Sibship index values were less than 1 in all 20 pairs of unrelated children. Sibship index values were greater than 100 in nine pairs of siblings (45%), between 10 and 100 in five pairs (25%), between 1 and 10 in four pairs (20%), and less than 1 in two pairs (10%). Siblings shared two alleles in 17 of 60 observations (28.3%); controls shared two alleles in 0 of 60 observations (0%). CONCLUSION: The sharing of one allele and the sharing of no alleles at a polymorphic locus of high heterozygosity provide limited information for and against sibship, respectively. The sharing of two alleles produces strong evidence favoring sibship. In a given case, the study of more than three polymorphic loci of high heterozygosity may be needed to develop the evidence that two people are siblings. The general logic and methods used for siblings apply to kinship analyses of other two-person pedigrees.     

Long-term intraocular pressure control by trabeculectomy: a ten-year life table

A retrospective study of 179 eyes in 127 patients who underwent trabeculectomy at Sydney Eye Hospital under the supervision of two surgeons between 1977 and 1982 was carried out. Survival analysis by life table method shows cumulative two, five, and 10 year success rates to be 78%, 70%, and 67% respectively, with mean duration of intraocular pressure control (IOP<21 mmHg) being 88 months. Anti-glaucoma medication improved the long-term survival significantly (Hazard Ratio of 0.49 and P = 0.01) so that when the definition for failure is taken as IOP >20 mmHg while using medication, the two, five and 10 year success rates were 89%, 87% and 86% respectively. A rise in average intraocular pressure is seen between two weeks and three months after trabeculectomy. The improvement in long-term success rate with use of topical steroids was suggestive (Hazard Ratio of 0.69) but not conclusive (P = 0.21). No difference was found in survival comparing fornix versus limbal based flap technique.     

Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents

More rapid skeletal maturation in African‐American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non‐obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed‐longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand‐wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual‐energy X‐ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self‐reported AA girls (～0.33 years, p < 0.001) and boys (～0.43 years, p < 0.001). Boys and girls of all ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self‐report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self‐report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non‐obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research.     

异体软组织修复材料在口腔颌面部缺损中的应用

目的 探讨异体软组织修复材料(异体脱细胞真皮基住)在口腔颌面外科应用的可行性。方法 选择口腔粘膜组织缺损患者46例，在创面上采用异体脱细胞真皮基质覆盖，并对修复后创面情况和组织病理进行观察。结果 所有口腔粘膜创面愈合良好，无1例出现排斥反应。经4～6月后组织学观察，异体脱细胞真皮基质处所生成的组织与正常粘膜组织不易区分。结论 异体脱细胞真皮基质可以作为口腔粘膜缺损的修复材料推广使用。     

Murine leukemia inhibitory factor enhances retroviral-vector infection efficiency of hematopoietic progenitors

We have investigated the in vitro effects of the cytokine leukemia inhibitory factor (LIF) on normal murine hematopoietic progenitors by measuring recovery and retroviral vector infection efficiency of 13-day posttransplant, spleen-colony-forming cell (CFU-S 13) in short-term culture. Up to a twofold increase in CFU-S13 recovery was observed, from 9.7 x 10(-5) cells in untreated controls to 17.8 to 19.5 x 10(-5) cells, depending on the concentration of LIF. Histologic analysis of spleen colonies from control and LIF-treated marrows demonstrated that there was no detectable alteration in the differentiative potential of CFU-S13. The efficiency of CFU-S13 infection was increased from 15% in untreated controls to 84% to 91% in LIF-treated marrows. Analysis of proviral integration sites in spleen colonies indicated that some CFU- S13 precursors were infected in the LIF-treated marrows.     

Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders

Autism spectrum disorder (ASD) represents a set of neurodevelopmental disorders with a strong genetic aetiology. Chromosomal rearrangements have been detected in 5–10% of the patients with ASD, and recent applications of array comparative genomic hybridisation (aCGH) are identifying further candidate regions and genes. In this study, we present four patients who implicate microcephalin 1 ( MCPH1) in band 8p23.1 as an ASD susceptibility gene. Patient 1 was a girl with a syndromic form of autistic disorder satisfying the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Oligonucleotide aCGH (oaCGH) showed that she had a classic inv dup del(8)(qter-> p23.1::p23.1-> p21.2) containing at least three candidate genes; MCPH1 and DLGAP2 within the 6.9-Mb terminal deletion and NEF3 within the concomitant 14.1-Mb duplication. Three further patients with MCPH1 copy number changes were found using single-nucleotide polymorphism (SNP) array analysis in a cohort of 54 families with ASD patients. Our results show that ASD can be a component of the classical inv dup del(8) phenotype and identify changes in copy number of MCPH1 as a susceptibility factor for ASD in the distal short arm of chromosome 8.     

Cost-utility analysis of genetic screening in families of patients with germline <Emphasis Type="Italic">MUTYH</Emphasis> mutations

Background  

MUTYH associated polyposis (MAP) is an autosomal recessive inherited disorder. Carriers of bi-allelic MUTYH germline mutations have a risk of approximately 60% to develop colorectal carcinoma (CRC). In the general population about 1.5% is a heterozygous MUTYH mutation carrier. Children of MAP patients have an increased risk of inheriting two MUTYH mutations compared to the general population, implicating an increased risk for developing CRC.     

Analysis of vancomycin use and associated risk factors in a university teaching hospital: a prospective cohort study

Background  

Vancomycin use is considered inappropriate in most hospitals. A particular concern is the recent emergence of S. aureus with decreased susceptibility to vancomycin, making it important to reduce overall exposure to vancomycin to minimize the incidence of VRE (vancomycin-resistant enterococci). The aim of this work was to analyze the use of vancomycin and the risk factors associated with inappropriate treatment.