Optimal Selection of Sib Pairs from Random Samples for Linkage Analysis of a QTL Using the EDAC Test

Percentages of extremely concordant and extremely discordant sib pairs are calculated that maximize the power to detect a quantitative trait locus (QTL) under a variety of circumstances using the EDAC test. We assume a large fixed number of randomly sampled sib pairs, such as one would hope to find in the large twin registries, and limited resources to genotype a certain number of selected sib pairs. Our aim is to investigate whether optimal selection can be achieved when prior knowledge concerning the QTL gene action, QTL allele frequency, QTL effect size, and background (residual) sib correlation is limited or absent. To this end we calculate the best selection percentages for a large number of models, which differ in QTL gene action allele frequency, background correlation, and QTL effect size. By averaging these percentages over gene action, over allele frequency, over gene action, and over allele frequencies, we arrive at general recommendations concerning selection percentages. The soundness of these recommendations is subsequently in a number of test cases.     

Histologic Findings One Year After Positive Crossmatch or ABO Blood Group Incompatible Living Donor Kidney Transplantation

Recent protocols have allowed successful positive crossmatch (+XM) and ABO incompatible (ABOI) kidney transplantation, although their long-term outcome is not clear. To begin to assess this issue we compared protocol biopsies performed 12 months posttransplant in 37 +XM, 24 ABOI and 198 conventional allografts. Although the majority in all three groups had only minimal histologic changes, transplant glomerulopathy (TG) was significantly increased in +XM (22% vs. 13% ABOI vs. 8% conventional, p = 0.015), and correlated with prior humoral rejection (HR) by multivariate analysis (odds ratio 17.5, p < or = 0.0001). Patients with a prior history of HR also had a significant increase in interstitial fibrosis (No HR 54% vs. HR 86%, p = 0.045). In the absence of HR no difference in histologic changes was seen between groups, although all three groups had a demonstrable mild increase in interstitial fibrosis from biopsies performed at the time of transplant. Thus, although HR is associated with an increase in TG, in its absence allograft histology is similar in +XM, ABOI and conventional allografts 1 year posttransplant.     

Desensitization protocols improving access and outcome in transplantation

Sensitization to antigens of the HLA and ABO system has been the biggest barrier to access in renal transplantation and, increasingly, in transplantation of other organs. Additionally, antibody to donor antigens has been shown to result in injury to the graft ranging from catastrophic, irreversible hyperacute rejection to the slower, more insidious, chronic form of rejection. The problem of access has been recognized globally and has been the incentive for measures to overcome the disadvantage experienced by the sensitized patient. However, early attempts to reduce sensitization achieved only transient success. Newer immunosuppressive agents that affect B-cell function or viability have permitted the development of treatment protocols to eliminate and, potentially, downregulate donor-specific antibodies. The use of these protocols has achieved successful transplants that were HLA and/or ABO incompatible prior to treatment and, as such, has provided some patients with their only opportunity for transplantation.     

中医药在糖尿病胃轻瘫治疗中的应用及思考

糖尿病胃轻瘫（DGP）发病率较高,药物治疗存在一定的局限性,部分患者可能出现一定的不良反应,这影响糖尿病的治疗。中药治疗DGP可以有效缓解患者症状,降低现有药物不良反应,辅助控制血糖。现代医家多利用辨证分型组方、经方验方及中成药进行辨病辨证治疗相结合,运用单味药、药对、中药提取物进行个体化治疗。现通过概述中药的多种组方思路,总结其优势,并对中药治疗DGP的现状进行思考与总结,以期中医药治疗DGP得到更好的发挥。     

半楼贝蔹及配伍乌头对大鼠肝细胞色素P450酶含量的影响

[目的]研究中药十八反中半夏、贝母、栝楼、白蔹、白及配伍乌头对大鼠肝细胞色素P450 酶含量的影响。[方法]采用紫外分光光度测定大鼠肝微粒体细胞色素P450与细胞色素b5含量。[结果]配伍组与其相应单药组比较可显著降低P450酶及b5含量(P<0.001或P<0.05)。[结论]药物配伍后导致P450酶变化 ,对药物的代谢产生影响。     

Hippocampal and medial prefrontal cortical volume is associated with overnight declarative memory consolidation independent of specific sleep oscillations

The current study was designed to further clarify the influence of brain morphology, sleep oscillatory activity and age on memory consolidation. Specifically, we hypothesized, that a smaller volume of hippocampus, parahippocampal and medial prefrontal cortex negatively impacts declarative, but not procedural, memory consolidation. Explorative analyses were conducted to demonstrate whether a decrease in slow‐wave activity negatively impacts declarative memory consolidation, and whether these factors mediate age effects on memory consolidation. Thirty‐eight healthy participants underwent an acquisition session in the evening and a retrieval session in the morning after night‐time sleep with polysomnographic monitoring. Declarative memory was assessed with the paired‐associate word list task, while procedural memory was tested using the mirror‐tracing task. All participants underwent high‐resolution magnetic resonance imaging. Participants with smaller hippocampal, parahippocampal and medial prefrontal cortex volumes displayed a reduced overnight declarative, but not procedural memory consolidation. Mediation analyses showed significant age effects on overnight declarative memory consolidation, but no significant mediation effects of brain morphology on this association. Further mediation analyses showed that the effects of age and brain morphology on overnight declarative memory consolidation were not mediated by polysomnographic variables or sleep electroencephalogram spectral power variables. Thus, the results suggest that the association between age, specific brain area volume and overnight memory consolidation is highly relevant, but does not necessarily depend on slow‐wave sleep as previously conceptualized.     

Full-Field Strain Mapping at a Ge/Si Heterostructure Interface

The misfit dislocations and strain fields at a Ge/Si heterostructure interface were investigated experimentally using a combination of high-resolution transmission electron microscopy and quantitative electron micrograph analysis methods. The type of misfit dislocation at the interface was determined to be 60° dislocation and 90° full-edge dislocation. The full-field strains at the Ge/Si heterostructure interface were mapped by using the geometric phase analysis (GPA) and peak pairs analysis (PPA), respectively. The effect of the mask size on the GPA and PPA results was analyzed in detail. For comparison, the theoretical strain fields of the misfit dislocations were also calculated by the Peierls-Nabarro and Foreman dislocation models. The results showed that the optimal mask sizes in GPA and PPA were approximately three tenths and one-tenth of the reciprocal lattice vector, respectively. The Foreman dislocation model with an alterable factor a = 4 can best describe the strain field of the misfit dislocation at the Ge/Si heterostructure interface.     

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility.Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant.ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression.ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.     

Low rates of anti-recipient isohemagglutinins in ABO incompatible hematopoietic stem cell transplants

IntroductionIsohemagglutinins occur naturally and form in an 'opposite' (antigen-negative) pattern to a patient’s ABO blood type. Patients undergoing minor and bidirectional ABO incompatible hematopoietic stem cell transplantation (HSCT) may demonstrate detectable antibodies against their native blood type. In this study, we sought to characterize the rates of such antibody formation and evaluate the clinical significance of our findings.Materials and MethodsAn internal database of HSCT patients at an academic medical center was queried for ABO incompatible transplant patients from 2009-2019. Serum typing results, clinical histories, and laboratory data were compiled and reviewed.ResultsA total of 182 minor and bidirectional ABO incompatible HSCT patients were identified. Anti-recipient isohemagglutinins were found in 9% (16/182) of the HSCT patients. The rate was higher in patients with minor incompatibility (12%: 15/127) versus bidirectional ABO incompatibility (2%: 1/55) (p = 0.04). No anti-recipient isohemagglutinins were identified in umbilical cord HSCT patients (0%: 0/7). Serologic agglutination reactions of recipient isohemagglutinins were overall mostly weak (13/16 weak + to 1+). There was a trend towards a higher rate of acute graft-versus-host-disease in patients with anti-recipient isohemagglutinins compared to those without (75% vs. 53%; p = 0.12), though not statistically significant. Rates of alloimmunization to minor red cell antigens were similar between the two groups. Few patients showed laboratory evidence of hemolysis at 12 months follow up.Discussion and conclusionsAnti-recipient isohemagglutinins occur at low rates in ABO incompatible HSCT and are significantly more common in minor ABO incompatible transplant compared to bidirectional transplants. Larger cohort studies are needed to better understand the relationship between anti-recipient isohemagglutinins and HSCT outcomes.