Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

HLA-DR mismatching correlates with early cardiac allograft rejection, incidence, and graft survival when high-confidence-level serological DR typing is used

To determine if cardiac allograft outcome is improved among patients with fewer HLA-DR mismatches with their donors, we studied 132 recipients of a primary cardiac allograft who were transplanted between December 1985 and December 1991. These recipients and their donors all had high-confidence-level serological HLA-DR typing, previously shown to correlate highly with DNA DR typing. Patients were divided in two groups based on the HLA-DR mismatch with their donors. Group I consisted of 78 patients with 1 or zero DR mismatch and group II of 54 patients with 2 DR mismatches. Allograft outcome measurements included incidence of moderate rejection, incidence of allograft vasculopathy at 12 months, cardiac function measured as left ventricular ejection fraction (LVEF) and cardiac index (CI), and actuarial graft survival up to 7 years. Groups I and group II were not different with regard to recipient age, donor age, ischemia time, pulmonary vascular resistance, sex, or PRA greater than 0%. Group II had a higher incidence of moderate rejection on the first-week biopsy (47% vs. 25%, P = 0.019), and during the first month (84% vs. 58%, P = 0.006), but no difference was found in frequency of rejection from months 2 to 12. LVEF was not different in the groups at any point. CI was better in group I at 12 months (2.76 vs. 2.5, P = 0.03). No statistically significant difference was found in incidence of allograft vasculopathy (17% vs. 26%, P = 0.204). Actual graft survival at 1 year was better for group I (91% vs. 74%, P = 0.008), and actuarial graft survival at 6 years also favored group I (76% vs. 56%, P = 0.04). Using high-confidence-level serological HLA-DR typing assignments we demonstrated that HLA-DR mismatching correlates highly with cardiac allograft outcome. Implications are that heart transplant survival could be improved if prospective matching were feasible and prioritized or if immunosuppression were tailored to the HLA-DR match.     

Recent advances in raisingT c and establishing the gap-symmetry of high-T c cuprate superconductors

The most recent attempts in raising T_c of cuprate superconductors were successful by synthesizing new Hg-based cuprate materials. We discuss some properties of materials from this series with varying numbers of Cu-O planes per unit cell, including the considerable rise of the critical temperature under the influence of external pressure.In the second part of this contribution, various attempts to directly determine the symmetry of the superconducting order parameter of high-T_c cuprates are mentioned and set into perspective. The experimental approaches are all based on probing the phase of the order parameter in suitably connected closed superconducting loops. The evidence for unconventional order-parameter symmetry in these materials is growing.     

Superconductivity in heavy-electron metals

Some of the most outstanding experimental evidences for unconventional superconductivity in heavy-electron materials are rewiewed and discussed.     

Interpretation of the results of the CORA-33 dry core boiling water reactor test

All boiling water reactor (BWR) degraded core experiments performed prior to CORA-33 were conducted under ‘wet’ core degradation conditions, in which water remains within the core and continuous steaming feeds metal-steam oxidation reactions on the in-core metallic surfaces. However, one dominant set of accident scenarios would occur with reduced metal oxidation under ‘dry’ core degradation conditions and, prior to CORA-33, this set had been neglected experimentally. The CORA-33 experiment was designed specifically to address this dominant set of BWR ‘dry’ core severe accident scenarios and to resolve partially phenomenological uncertainties concerning the behavior of relocating metallic melts that drain into the lower regions of a ‘dry’ BWR core (the ex-reactor experiments at Sandia National Laboratories will further address these uncertainties). CORA-33 was conducted on 1 October 1992, in the CORA test facility at Karlsruhe. A review of the CORA-33 data indicates that the objectives were achieved; i.e. core degradation occurred at a core heat-up rate (characterized by the absence of any temperature escalation caused by oxidation) and a test section axial temperature profile (at incipient structural melting) that are prototypic of full-core nuclear power plant simulations under ‘dry’ core conditions. Simulations of the CORA-33 test at Oak Ridge National Laboratory (ORNL) have required the modification of existing control blade-canister materials interaction models to include the eutectic melting of the stainless steel-zircaloy interaction products and the heat of mixing of stainless steel and zircaloy. The timing and location of canister failure and melt intrusion into the fuel assembly appear to be adequately simulated by the ORNL models. This paper will present the results of the post-test analyses carried out at ORNL based on the experimental data and the post-test examination of the test bundle at Karlsruhe. The implications of these results with respect to degraded core modelling and the associated safety issues are also discussed.     

Microstructural development and creep deformation in equiaxed γ, γ+α 2, and γ+α 2+B2 titanium aluminides

The development of microstructure and its influence on creep properties have been studied for structures including equiaxed γ, duplex, and other structures of varying α ₂ morphology in two Ti-48Al-2Cr-2Nb alloys. Heat treatments at 1125 °C have been utilized to produce equiaxed γ microstructures in alloys with or without Mo additions. The γ → α transformation produces α ₂ plates with several orientation variants within γ grains during subsequent annealing of the equiaxed γ microstructures below the α transus. Formation of this α ₂ morphology results from rapid up-quenching (UQ), and this structure persists through annealing, cooling, and creep testing. Differences in minimum creep rates for several microstructures containing varying amounts of multi- or single variant γ/α ₂ grains are shown to be minimal. The presence of Mo has also resulted in improved creep resistance in equiaxed γ and γ+α ₂+B2 structures, as compared to similar microstructures in the Ti-48Al-2Cr-2Nb alloy. Deformation during creep at 760 °C at stresses between 200 and 400 MPa occurs by a combination of twinning and dislocation glide without recrystallization, resulting in power-law stress exponents in the range of 6 to 9. Only minimal strain path dependence of the minimum creep rate is detected in a comparison of creep rates in stress jump, stress drop, and single stress tests. This article is based on a presentation made in the symposium “Fundamentals of Gamma Titanium Aluminides,” presented at the TMS Annual Meeting, February 10–12, 1997, Orlando, Florida, under the auspices of the ASM/MSD Flow & Fracture and Phase Transformations Committees.