Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia

OBJECTIVE: Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs. RESEARCH DESIGN AND METHODS: This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time. RESULTS: Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23–3.50) compared with current metformin use. CONCLUSIONS: Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.Merck SA, Lyon, Franc

Use of depot medroxyprogesterone acetate and fracture risk

Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited.; We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk.; We conducted a case-control analysis using the United Kingdom-based General Practice Research Database.; Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008.; Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders.; We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (<2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1.; This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures

Precise measurements of electron and hole g-factors of single quantum dots by using nuclear field

We demonstrated the cancellation of the external magnetic field by the nuclear field at one edge of the nuclear polarization bistability in single InAlAs quantum dots. The cancellation for the electron Zeeman splitting gives the precise value of the hole g-factor. By combining with the exciton g-factor that is obtained from the Zeeman splitting for linearly polarized excitation, the magnitude and sign of the electron and hole g-factors in the growth direction are evaluated.Comment: 3 pages, 2 figure

Building CMS Pixel Barrel Detectur Modules

For the barrel part of the CMS pixel tracker about 800 silicon pixel detector modules are required. The modules are bump bonded, assembled and tested at the Paul Scherrer Institute. This article describes the experience acquired during the assembly of the first ~200 modules.Comment: 5 pages, 7 figures, Vertex200

Extended Variability of the Symbiotic Star AG Draconis

We have analyzed the complete set of available IUE (International Ultraviolet Explorer) spectra for the symbiotic star AG Draconis covering the period from 1979 to 1989. All absolute line fluxes and wavelengths have been obtained for the prominent emission lines in the λλ1200-3200 wavelength range. These spectra contain observations which were taken before, during and after the two extended outbursts which occurred on 1980 November to 1981 November and 1985 February to 1986 January. These two outburst events have two maxima that are separated by ~1600 days, a time scale not known to be associated with the star, but which is ~3 times the binary period of the star. 0 IV] λλ1397-1407 emission line intensities imply an electron density in the range 10^10 ≤ ne ≤ 10^11 cm^-3. We found the line-emitting region to have a linear size 10^12 ≤ L ≤ 10^13 cm. The He II A1640 Zanstra method yields T ≥ 87,000 K for the hot component. Absolute line intensities are plotted as a function of Julian Date for the principal emission lines of N v λλ1238, 1242,0 I λλ1302-1306, 0 IV] λλ1397-1407, C IV λλ1548, 1550, He II A1640 and 0 m] λλ1660, 1666 to observe the temporal variability of AG Dra. Emission line fluxes of N v, 0 1, N IV], C IV, and N III] are plotted as a function of C IV to study the nature of the emitting regions. We have calculated the nitrogen ionic abundances for AG Dra to study how the ionization levels change during outburst and quiescence phases of the star. The time-evolution of the calculated ionic abundances shows the presence of abundance peaks coincident with the outburst events and the binary phases favoring episodic mass transfers onto the compact star. Monitoring, preferably every 3 to 4 years could be helpful in confirming the accretion-powered outburst mechanism of this star and provide important insights into the symbiotic phenomenon in general

Ultraviolet Temporal Variability of the Peculiar Star R Aquarii

This paper is a comprehensive study of all far-UV spectra obtained with the International Ultraviolet Explorer (IUE) satellite of the symbiotic star R Aquarii (R Aqr) covering a 13 yr period between 1979 and 1992. We have analyzed the ultraviolet emission for the compact H II region and the NE and SW extended jetlike filamentary structures. The results of our ultraviolet analysis indicate that the H II region and features A, B, and D of the NE jet are increasing in intensity, while the SW counterjet, feature A\u27, has declined in intensity. We have found much stronger evidence that the high ionization lines of N v λλ1238, 1240 and He II λ1640 in the H II region and NE jet have steadily increased over the entire period of IUE observations. This result could indicate that the ionized region is increasing in excitation. We have found that the observations of the NE jet are consistent with a decreasing electron temperature and increasing line-emitting region, which suggest that the strengthening of emission-line fluxes may be a result of an expanding emitting volume in a post-shocked region. Low-resolution absolute line intensities and wavelengths for the most prominent emission lines in the λλ1200-3200 wavelength range have been tabulated. In addition, we present plots of the total ultraviolet flux (λλ1200-3200) and absolute line intensities as a function of time to discern the temporal variability of R Aqr. These plots indicate that the far-UV emission from the NE jet is not variable on a ~1.5 yr timescale as suggested by Kafatos, Michalitsianos, & Hollis. Moreover, we find that the variations in the far-UV emission in R Aqr are not coupled to the 386 day pulsation period of the Mira. Finally, successive ionization levels of carbon, nitrogen, oxygen, and silicon of the NE jet are compared with each other to probe the nature of the ionization source in the NE jet. High- and low-resolution ultraviolet spectra were used to calculate the properties of the emission nebula and hot component. We determined electron densities of ne = 4 x 10^5 cm^-3 (H II region) and ne = 6 x 10^4 cm^-3 (NE jet), electron temperatures of Te ~ 20,000 K (H II region) and a high value of Te ≥ 26,000 K between 1982 May and 1983 December, to a low value of Te ≤ 18,000 K from observations during the period of 1986 December and 1989 June (NE jet), and also line-emitting regions of L = 6.3 x 10^14 cm (H II region) and L = 1.5 x 10^15 cm (NE jet). The He II λ1640 modified Zanstra method yielded an effective temperature of T* = 61,000 K for the hot component. Estimates of the number of ionizing photons beyond the Lyman limit, blackbody parameters, and possible accretion disk parameters for the hot component are also given

The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog

We show that desert hedgehog ( dhh), a signaling molecule expressed by Schwann cells, is essential for the structural and functional integrity of the peripheral nerve. Dhh-null nerves display multiple abnormalities that affect myelinating and nonmyelinating Schwann cells, axons, and vasculature and immune cells. Myelinated fibers of these mice have a significantly increased ( more than two times) number of Schmidt-Lanterman incisures ( SLIs), and connexin 29, a molecular component of SLIs, is strongly upregulated. Crossing dhh-null mice with myelin basic protein ( MBP)-deficient shiverer mice, which also have increased SLI numbers, results in further increased SLIs, suggesting that Dhh and MBP control SLIs by different mechanisms. Unmyelinated fibers are also affected, containing many fewer axons per Schwann cell in transverse profiles, whereas the total number of unmyelinated axons is reduced by approximately one-third. In dhh-null mice, the blood-nerve barrier is permeable and neutrophils and macrophage numbers are elevated, even in uninjured nerves. Dhh-null nerves also lack the largest-diameter myelinated fibers, have elevated numbers of degenerating myelinated axons, and contain regenerating fibers. Transected dhh nerves degenerate faster than wild-type controls. This demonstrates that a single identified glial signal, Dhh, plays a critical role in controlling the integrity of peripheral nervous tissue, in line with its critical role in nerve sheath development ( Parmantier et al., 1999). The complexity of the defects raises a number of important questions about the Dhh-dependent cell-cell signaling network in peripheral nerves