Solubility determination from clear points upon solvent addition

A method is described for determining the solubility of multicomponent crystalline compounds from clear points upon sample dilution at a constant temperature. Clear points are established by continuously adding a solvent mixture to a suspension of known composition until a clear solution appears. For validation, this solvent addition method is compared to the traditional equilibrium concentration method at constant temperature and the more recent temperature variation method with which clear point temperatures are determined upon increasing the sample temperature. Solubility data of binary systems (1 solute, 1 solvent) measured using the solvent addition method are obtained relatively quickly compared to the equilibrium concentration method. These solubility data are consistent with those of the temperature variation and the equilibrium concentration method. For the temperature variation method, the results are dependent on the heating rate. Likewise, for the solvent addition method, they are dependent on the addition rate. Additionally, for ternary systems involving antisolvent or cocrystals, solubilities are determined at a constant temperature using the solvent addition method. The use of the solvent addition method is especially valuable in the case of solvent mixtures and other complex multicomponent systems, in which the temperature variation method cannot be applied easily

The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction:data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial

Objective: In patients with diabetes mellitus, metformin treatment is associated with reduced mortality and attenuation of cardiovascular risk. As a subanalysis of the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) study, we evaluated whether metformin treatment in patients with ST-segment elevation myocardial infarction (STEMI) without diabetes improves the cardiovascular risk profile. Methods: A total of 379 patients, without known diabetes, presenting with STEMI were randomly allocated to receive metformin 500 mg twice daily or placebo for 4 months. Results: After 4 months, the cardiovascular risk profile of patients receiving metformin (n= 172) was improved compared with placebo (n= 174); glycated hemoglobin (5.83% (95% CI 5.79% to 5.87%) vs 5.89% (95% CI 5.85% to 5.92%); 40.2 mmol/mol (95% CI 39.8 to 40.6) vs 40.9 mmol/mol (40.4 to 41.2), p= 0.049); total cholesterol (3.85 mmol/L (95% CI 3.73 to 3.97) vs 4.02 mmol/L (95% CI 3.90 to 4.14), p= 0.045); low-density lipoprotein cholesterol (2.10 mmol/L (95% CI 1.99 to 2.20) vs 2.3 mmol/L (95% CI 2.20 to 2.40), p= 0.007); body weight (83.8 kg (95% CI 83.0 to 84.7) vs 85.2 kg (95% CI 84.4 to 86.1), p= 0.024); body mass index (26.8 kg/m(2) (95% CI 26.5 to 27.0) vs 27.2 kg/m(2) (95% CI 27.0 to 27.5), p= 0.014). Levels of fasting glucose, postchallenge glucose, insulin, high-density lipoprotein cholesterol, and blood pressure were similar in both groups. Conclusions: Among patients with STEMI without diabetes, treatment with metformin for 4 months resulted in a modest improvement of the cardiovascular risk profile compared with placebo

GRB 030329: 3 years of radio afterglow monitoring

Radio observations of gamma-ray burst (GRB) afterglows are essential for our understanding of the physics of relativistic blast waves, as they enable us to follow the evolution of GRB explosions much longer than the afterglows in any other wave band. We have performed a three-year monitoring campaign of GRB 030329 with the Westerbork Synthesis Radio Telescopes (WSRT) and the Giant Metrewave Radio Telescope (GMRT). Our observations, combined with observations at other wavelengths, have allowed us to determine the GRB blast wave physical parameters, such as the total burst energy and the ambient medium density, as well as investigate the jet nature of the relativistic outflow. Further, by modeling the late-time radio light curve of GRB 030329, we predict that the Low-Frequency Array (LOFAR, 30-240 MHz) will be able to observe afterglows of similar GRBs, and constrain the physics of the blast wave during its non-relativistic phase.Comment: 5 pages, 2 figures, Phil. Trans. R. Soc. A, vol.365, p.1241, proceedings of the Royal Society Scientific Discussion Meeting, London, September 200

Detailed study of the GRB 030329 radio afterglow deep into the non-relativistic phase

We explore the physics behind one of the brightest radio afterglows ever, GRB 030329, at late times when the jet is non-relativistic. We determine the physical parameters of the blast wave and its surroundings, in particular the index of the electron energy distribution, the energy of the blast wave, and the density (structure) of the circumburst medium. We then compare our results with those from image size measurements. We observed the GRB 030329 radio afterglow with the Westerbork Synthesis Radio Telescope and the Giant Metrewave Radio Telescope at frequencies from 325 MHz to 8.4 GHz, spanning a time range of 268-1128 days after the burst. We modeled all the available radio data and derived the physical parameters. The index of the electron energy distribution is p=2.1, the circumburst medium is homogeneous, and the transition to the non-relativistic phase happens at t_NR ~ 80 days. The energy of the blast wave and density of the surrounding medium are comparable to previous findings. Our findings indicate that the blast wave is roughly spherical at t_NR, and they agree with the implications from the VLBI studies of image size evolution. It is not clear from the presented dataset whether we have seen emission from the counter jet or not. We predict that the Low Frequency Array will be able to observe the afterglow of GRB 030329 and many other radio afterglows, constraining the physics of the blast wave during its non-relativistic phase even further.Comment: 9 pages, 2 figures; accepted for publication in Astronomy & Astrophysics after minor revisions; small changes in GMRT fluxes at 1280 MH

Longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders

Objective To examine longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Methods Follow-up data of 584 participants with remitted depressive or anxiety disorders were used from the Netherlands Study of Depressive and Anxiety disorders. Multiple physical symptoms were measured at baseline (T1) and two-year follow-up (T2) by the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale. Recurrence of depressive and anxiety disorders was assessed at two-year (T2) and four-year (T4) follow-up with the Composite International Diagnostic Interview. Logistic Generalized Estimating Equations were used to examine associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Depressive (IDS-SR) and anxiety symptoms (BAI), and other relevant covariates were taken into account. Results Multiple physical symptoms were significantly associated with recurrence of depression (OR = 1.04, 95%CI = 1.00–1.08), anxiety (OR = 1.07, 95%CI = 1.03–1.12), and depressive or anxiety disorders (OR = 1.06, 95%CI = 1.02–1.10), on average over time. Odds ratios did not change substantially when the IDS-SR mood-cognition and BAI subjective scale were included as covariates. Conclusion The presence of multiple physical symptoms was positively related to recurrence of depressive and anxiety disorders, independent of depressive and anxiety symptoms. Knowledge of risk factors for recurrence of depressive and anxiety disorders, such as the presence of multiple physical symptoms, could provide possibilities for better targeting interventions to prevent recurrence