Objectives: To compare bone mineral density (BMD) and body proportions between women with complete androgen insensitivity syndrome (CAIS) and with gonadal dysgenesis (GD). Setting: Adult Disorders of Sexual Development and Ovarian Failure Clinics at University College London Hospitals. Design: Retrospective cross-sectional study of three groups of women aged 17-58 years with varying degrees of exposure to sex hormones and different combinations of sex chromosomes. Forty-six subjects had CAIS, 18 had GD and 46,XY (GD(XY)), and 25 had GD and 46,XX (GD(XX)). In addition, body proportions of subgroups of these women were analysed. Outcome measures: Oestrogen therapy, karyotype, anthropometry and BMD. Results: Height differed between groups (F ratio 5.2, PZ0.007)), with GD(XX) women being the shortest (meanGS.D.: 1.66G0.10 m), GD(XY) women the tallest (1.74G0.09 m) and CAIS women were in-between (1.70G0.07 m). Delayed gonadectomy resulted in taller stature in CAIS women (PZ0.011). The ratio of lower to upper body length in GD(XY) women was significantly (PZ0.001) greater than that of CAIS women. Multivariate logistic regression analysis (adjusted for age and height) showed that among women with XY karyotype, GD(XY) women were 5.2 times (95% confidence interval (CI): 1.3-20.1, PZ0.018) more likely than CAIS women to have a low hip BMD. This difference was not evident among women with GD of different karyotypes (PZ0.938). Spinal BMD did not differ between subject groups. Further adjustment for oestrogen replacement did not alter these relationships. Conclusions: Taller stature in late gonadectomised CAIS women suggests an oestrogen deficiency in these women prior to gonadectomy. Increased lower to upper body ratio in GD(XY) women compared with the other groups implies that these subjects have the greatest degree of oestrogen deficiency in puberty. Androgen rather than sex chromosomes may play an important role in cortical bone mineralisation in CAIS women, probably via estrogen receptor-a either directly or via aromatisation during critical periods of growth prior to gonadectomy.
On the basis of simulation results, adding dapagliflozin to currently available treatment options is projected to further decrease the CV and microvascular complications associated with T2DM.
We used the Archimedes Model, a mathematical simulation model (Model) to estimate the clinical- and cost-effectiveness of using LDL particle concentration (LDL-P) as an adjunct or alternative to LDL cholesterol (LDL-C) to guide statin therapy. LDL-P by NMR has been shown to be a better measure of cardiovascular disease (CVD) risk than LDL-C, and may therefore be a better gauge of the need for and response to statin treatment. Using the Model, we conducted a virtual clinical trial comparing the use of LDL-C alone, LDL-P alone, and LDL-C and LDL-P together to guide treatment in the general adult population, and in high-risk, dyslipidemic subpopulations. In the general population, the 5-year major adverse cardiovascular event (MACE) relative risk reduction (RRR) of LDL-P alone compared to the control arm (LDL-C alone) was 5.0% (95% CI, 4.7-5.3; p < .0001); using both LDL-C and LDL-P (dual markers) led to 3.0% RRR compared to the control arm (95% CI, 2.8-3.3; p < .0001). For individuals with diabetes, the RRR was 7.3% (95% CI, 6.4-8.2; p < .0001) for LDL-P alone and 6.9% for dual markers (95% CI, 6.1-7.8; both, p < .0001). In the general population, the costs per quality-adjusted life year (QALY) associated with the use of LDL-P alone were $76,052 at 5 years and $8913 at 20 years and $142,825 at 5 years and $25,505 at 20 years with the use of both markers. In high-risk subpopulations, the use of LDL-P alone was cost-saving at 5 years; whereas the cost per QALY for the use of both markers was $14,250 at 5 years and $859 at 20 years for high-risk dyslipidemics, $19,192 at 5 years and $649 at 20 years for diabetics, and $9030 at 5 years and $7268 at 20 years for patients with prior CHD. In conclusion, the model estimates that using LDL-P to guide statin therapy may reduce the risk of CVD events to a greater extent than does the use of LDL-C alone and maybe cost-effective or cost-saving for high-risk patients.
Understanding the benefit versus risk of glycemic control and hypoglycemia is fundamental to the successful management of patients with T2DM. Our validated hypoglycemia model is an important step in addressing this issue and may be helpful to researchers, clinicians, and payers to determine the patients who are at the highest risk for hypoglycemia, whether a patient is experiencing events at 'higher-than-expected' rates, and the corresponding economic burden.
Magnetic tunnel junctions (MTJs) based on fully spin polarized ferromagnetic manganites have generated a lot of interest due to their enhanced field sensitivity at low temperatures. However, the tunneling magnetoresistance (TMR) drops rapidly with increasing temperature due to the reduction of spin polarization at the manganite-insulator interface. We have devised a method for creating intrinsic tunnel barriers by tuning the phase competition in manganites using substrate induced strain. Ultrathin films (7.5nm) of the mixed phase manganite (La0.5Pr0.5)0.67Ca0.33MnO3 (LPCMO) grown on the substrate (110) NdGaO3 using pulsed laser deposition show positive magnetoresistance (MR) of about 30% at magnetic fields less than 1T. Unlike the fabricated MTJ devices, this MR effect has its maximum value close to the insulator to metal transition temperature and reduces with decreasing temperature. To find out the mechanism leading to this positive MR, the effect of three orientations of the magnetic field on the LPCMO thin films were studied: (1) perpendicular to the plane of the film, (2) parallel to the plane of the film and applied current, and (3) parallel to the plane of the film but perpendicular to the applied current. The effect of field orientation suggests that a possible mechanism for the positive MR is tunneling magnetoresistance due to the spin conserving tunneling process across the insulating regions separating the ferromagnetic metallic regions. The voltage dependence of the MR also supports this mechanism. Our results suggest a novel method for obtaining enhanced TMR in manganite based MTJs by creating strain induced intrinsic tunnel barriers.
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