Aim
To assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise.
Methods
This phase III, double‐blind, ...placebo‐controlled, multicentre study included 192 patients randomized to once‐daily treatment with fasiglifam 25 mg (n = 63) or 50 mg (n = 62) or placebo (n = 67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24.
Results
At week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p < 0.0001). The least squares mean change from baseline in HbA1c was 0.16% with placebo, −0.57% with fasiglifam 25 mg and −0.83% with fasiglifam 50 mg. The percentage of patients who achieved an HbA1c target of <6.9% at week 24 was also significantly higher (p < 0.05) for fasiglifam 25 mg (30.2%) and 50 mg (54.8%) compared with placebo (13.8%). Fasiglifam significantly reduced fasting plasma glucose levels at all assessment points, starting from week 2. The incidence and types of treatment‐emergent adverse events in each fasiglifam group were similar to those in the placebo group, and hypoglycaemia was reported in 1 patient receiving fasiglifam 50 mg. There were no clinically meaningful changes in body weight in any treatment group.
Conclusions
Fasiglifam significantly improved glycaemic control and was well tolerated, with a low risk of hypoglycaemia in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed.
Dismemberment and subsequent burning are common methods employed in an attempt to conceal or destroy evidence. While kerf characteristics can be utilised to identify tool(s) used for dismemberment, ...further research is necessary to assess the effect of burning on these characteristics. In this study, a back (tenon) saw (13 teeth per inch) was used to manually inflict trauma on Ovis aries de-fleshed femur bones (n = 18). Three different cut marks (shallow false start, incomplete cut and complete transection) were made on the mid-shaft of each bone. Subsequently, the bones were burned for 20 minutes in a muffle furnace. Three burn temperatures were assessed: 400 °C, 600 °C and 800 °C. Saw mark characteristics of each cut type were assessed and compared pre- and post-burning. All pre-existing trauma was recognisable post-burning; however, metric and morphological alterations were apparent. An increase in kerf width was observed at 600 °C in false start lesions and 800 °C in incomplete cuts. Breakaway spur thickness decreased post-burning (at 400 °C and 800 °C) but length was not significantly affected. Mean inter-striation distance decreased post burning at all temperature groups. Saw marks were distinguishable from heat-related fractures across all temperature groups. One false start lesion was obliterated at 800 °C. Exit chipping, pull-out striae as well as striation regularity appeared to be more enhanced after heat exposure. These alterations indicate a temperature-dependent impact on these characteristics. Further research is necessary to assess the role of burn duration.
•Increased fracturing and fragility in burnt bones with increased burn temperature.•Saw mark characteristics more evident in burned compared to unburnt bones.•Significant increase in kerf width and decrease in kerf depth at 800°C.
This multicentre, open‐label, phase III study investigated the safety and efficacy of the G‐protein‐coupled receptor 40 agonist fasiglifam. Japanese patients with type 2 diabetes and inadequate ...glycaemic control despite diet and/or exercise (n = 282), or despite diet and/or exercise plus one oral antidiabetic agent sulphonylurea (n = 262), rapid‐acting insulin secretagogue (n = 124), α‐glucosidase inhibitor (n = 141), biguanide (n = 136), thiazolidinedione (n = 139) or dipeptidyl peptidase‐4 inhibitor (n = 138) were randomized to treatment with fasiglifam 25 or 50 mg once daily for 52 weeks. The primary endpoints were safety variables. The overall incidence of treatment‐emergent adverse events (TEAEs) was 75.4–85.1% in the 25 mg group and 78.9–89.9% in the 50 mg group; most TEAEs were mild. Hypoglycaemia was negligible with fasiglifam monotherapy and most common with sulphonylurea combination therapy (12.4 and 9.1% for 25 and 50 mg groups, respectively). Abnormal liver‐related laboratory values were uncommon. Glycated haemoglobin levels decreased from week 2 in all groups and were maintained to week 52. Although fasiglifam as monotherapy or in combination regimens was well tolerated during long‐term treatment, global concerns about liver safety led to termination of its development after study completion.
We present new data for five underluminous Type II-plateau supernovae (SNe IIP), namely SN 1999gn, SN 2002gd, SN 2003Z, SN 2004eg and SN 2006ov. This new sample of low-luminosity SNe IIP (LL SNe IIP) ...is analysed together with similar objects studied in the past. All of them show a flat light-curve plateau lasting about 100 d, an underluminous late-time exponential tail, intrinsic colours that are unusually red, and spectra showing prominent and narrow P Cygni lines. A velocity of the ejected material below 103 km s−1 is inferred from measurements at the end of the plateau. The 56Ni masses ejected in the explosion are very small (≤10−2 M). We investigate the correlations among 56Ni mass, expansion velocity of the ejecta and absolute magnitude in the middle of the plateau, confirming the main findings of Hamuy, according to which events showing brighter plateau and larger expansion velocities are expected to produce more 56Ni. We propose that these faint objects represent the LL tail of a continuous distribution in parameters space of SNe IIP. The physical properties of the progenitors at the explosion are estimated through the hydrodynamical modelling of the observables for two representative events of this class, namely SN 2005cs and SN 2008in. We find that the majority of LL SNe IIP, and quite possibly all, originate in the core collapse of intermediate-mass stars, in the mass range 10-15 M.
► We analyze failure probability of composites considering microscopic randomness. ► Both random variations of elastic properties and strength are considered. ► Accuracy of the proposed method is ...investigated compared with the MC simulation. ► Microscopic randomness of an elastic property causes increase of failure probability. ► The influence depends on macro and microscopic conditions and is complex.
This paper discusses a microscopic failure probability analysis of a microstructure in a composite material considering a microscopic randomness of both elastic properties and strength of component materials. Since a microscopic random variation of an elastic property of component materials will have an influence on a microscopic stress field, the influence of a microscopic random variation on a microscopic failure probability of a composite material should be investigated. For the analysis, the Monte-Carlo simulation, the perturbation-based stochastic homogenization method and a stochastic multiscale stress analysis method are employed. A random variation of the microscopic stresses and microscopic failure probability are estimated with the stochastic multiscale stress analysis methodology via the stochastic homogenization analysis.
With the numerical examples, the influence of the microscopic random variation on the microscopic failure probability thorough the multiscale stress analysis is discussed. Also, accuracy of the perturbation-based approach is investigated with comparison of the Monte-Carlo simulation.
Context. Little is known about the properties of the warm (Tdust ≳ 150 K) debris disk material located close to the central star, which has a more direct link to the formation of terrestrial planets ...than does the low-temperature debris dust that has been detected to date. Aims. To discover new warm debris disk candidates that show large 18 μm excess and estimate the fraction of stars with excess based on the AKARI/IRC Mid-Infrared All-Sky Survey data. Methods. We searched for point sources detected in the AKARI/IRC All-Sky Survey, which show a positional match with A-M dwarf stars in the Tycho-2 Spectral Type Catalogue and exhibit excess emission at 18 μm compared to what is expected from the KS magnitude in the 2MASS catalogue. Results. We find 24 warm debris candidates including 8 new candidates among A-K stars. The apparent debris disk frequency is estimated to be 2.8 ± 0.6%. We also find that A stars and solar-type FGK stars have different characteristics of the inner component of the identified debris disk candidates. While debris disks around A stars are cooler and consistent with steady-state evolutionary model of debris disks, those around FGK stars tend to be warmer and cannot be explained by the steady-state model.
For future space infrared astronomical coronagraphy, we perform experimental studies on the application of aluminum mirrors to a coronagraph. Cooled reflective optics is required for broadband ...mid-infrared observations in space, while high-precision optics are required for coronagraphy. For the coronagraph instrument originally proposed for the next-generation infrared astronomical satellite project SPICA (SCI: SPICA Coronagraph Instrument), we fabricated and evaluated the optics consisting of high-precision aluminum off-axis mirrors with diamond-turned surfaces, and conducted a coronagraphic demonstration experiment using the optics with a coronagraph mask. We first measured the wave front errors (WFEs) of the aluminum mirrors with a He-Ne Fizeau interferometer to confirm that the power spectral densities of the WFEs satisfy the SCI requirements. Then we integrated the mirrors into an optical system and evaluated the overall performance of the system. As a result, we estimate the total WFE of the optics to be 33 nm (rms), each mirror contributing 10-20 nm (rms) for the central 14 mm area of the optics, and obtain a contrast of 10-5.4 as a coronagraph in the visible light. At a wavelength of 5 μm, the coronagraphic system is expected to achieve a contrast of ∼10-7 based on our model calculation with the measured optical performance. Thus our experiment demonstrates that aluminum mirror optics is applicable to a highly WFE-sensitive instrument such as a coronagraph in space.
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