Aims
In people with metformin‐treated diabetes, to evaluate the risk of acute pancreatitis, pancreatic cancer and other diseases of the pancreas post second‐line anti‐hyperglycaemic agent initiation.
...Methods
People with Type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase‐4 inhibitor (DPP‐4i, n = 50 095), glucagon‐like peptide‐1 receptor agonist (GLP‐1RA, n = 12 654), sulfonylurea (n = 110 747), thiazolidinedione (n = 17 597) or insulin (n = 34 805) for at least 3 months were identified in the US Centricity Electronic Medical Records. Time to developing acute pancreatitis, other diseases of the pancreas and pancreatic cancer was estimated, balancing and adjusting anti‐hyperglycaemic drug groups for appropriate confounders.
Results
In the DPP‐4i group, the adjusted mean time to acute pancreatitis was 2.63 95% confidence intervals (CI) 2.38, 2.88 years; time to pancreatic cancer was 2.70 (2.19, 3.21) years; and time to other diseases of the pancreas was 2.73 (2.33, 3.12) years. Compared with DPP‐4i, the insulin group developed acute pancreatitis 0.48 years (P < 0.01) earlier and the GLP‐1RA group developed pancreatic cancer 3 years later (P < 0.01). However, with the constraint of no event within 6 months of insulin initiation, the risk of acute pancreatitis in the insulin group was insignificant. No other significant differences were observed between groups.
Conclusions
No significant differences in the risk of developing pancreatic diseases in those treated with various anti‐hyperglycaemic drug classes were found.
What's new?
Association of treatment with incretin‐based therapies and the risk of pancreatic diseases remains controversial. However, no study explored the comparative safety of different anti‐hyperglycaemic drugs in this context.
This study provides a holistic population‐level comparative outcome evaluation of the risk of pancreatic diseases from the time of receiving different second‐line anti‐hyperglycaemic drugs post metformin.
Although treatment with incretin‐based therapies was not found be to be associated with an increased risk of pancreatic diseases, people treated with insulin experienced higher risk of such diseases.
Based on over 4 years of Van Allen Probes measurements, an empirical model of radiation belt electron equatorial pitch angle distribution (PAD) is constructed. The model, developed by fitting ...electron PADs with Legendre polynomials, provides the statistical PADs as a function of L‐shell (L = 1–6), magnetic local time, electron energy (~30 keV to 5.2 MeV), and geomagnetic activity (represented by the Dst index) and is also the first empirical PAD model in the inner belt and slot region. For megaelectron volt electrons, model results show more significant day‐night PAD asymmetry of electrons with higher energies and during disturbed times, which is caused by geomagnetic field configuration and flux radial gradient changes. Steeper PADs with higher fluxes around 90° pitch angle and lower fluxes at lower pitch angles for higher‐energy electrons and during active times are also present, which could be due to electromagnetic ion cyclotron wave scattering. For hundreds of kiloelectron volt electrons, cap PADs are generally present in the slot region during quiet times and their energy‐dependent features are consistent with hiss wave scattering, while during active times, cap PADs are less significant especially at outer part of slot region, which could be due to the complex energizing and transport processes. The 90°‐minimum PADs are persistently present in the inner belt and appear in the slot region during active times, and minima at 90° pitch angle are more significant for electrons with higher energies, which could be a critical evidence in identifying the underlying physical processes responsible for the formation of 90°‐minimum PADs.
Key Points
Megaelectron volt electrons have steeper pitch angle distributions (PAD) during active times and for higher‐energy electrons, suggesting EMIC wave scattering
Cap PADs are generally present in the slot region during quiet times with energy‐dependent features consistent with hiss wave scattering
The 90°‐minimum PADs are persistently present in the inner belt, with more significant minima at 90° PA for electrons with higher energies
We present Hubble Space Telescope (HST) spectroscopy of the nucleus of M31 obtained with the Space Telescope Imaging Spectrograph (STIS). Spectra that include the Ca II infrared triplet (l 8500 Ae) ...see only the red giant stars in the double brightness peaks P1 and P2. In contrast, spectra taken at l 3600-5100 Ae are sensitive to the tiny blue nucleus embedded in P2, the lower surface brightness nucleus of the galaxy. P2 has a K-type spectrum, but we find that the blue nucleus has an A-type spectrum: it shows strong Balmer absorption lines. Hence, the blue nucleus is blue not because of AGN light but rather because it is dominated by hot stars. We show that the spectrum is well described by A0 giant stars, A0 dwarf stars, or a 200 Myr old, single-burst stellar population. White dwarfs, in contrast, cannot fit the blue nucleus spectrum. Given the small likelihood for stellar collisions, recent star formation appears to be the most plausible origin of the blue nucleus. In stellar population, size, and velocity dispersion, the blue nucleus is so different from P1 and P2 that we call it P3 and refer to the nucleus of M31 as triple. Because P2 and P3 have very different spectra, we can make a clean decomposition of the red and blue stars and hence measure the light distribution and kinematics of each uncontaminated by the other. The line-of-sight velocity distributions of the red stars near P2 strengthen the support for Tremaine's eccentric disk model. Their wings indicate the presence of stars with velocities of up to 1000 km s super(-1) on the anti-P1 side of P2. The kinematics of P3 are consistent with a circular stellar disk in Keplerian rotation around a supermassive black hole. If the P3 disk is perfectly thin, then the inclination angle i 55 is identical within the errors to the inclination of the eccentric disk models for P1+P2 by Peiris & Tremaine and by Salow & Statler. Both disks rotate in the same sense and are almost coplanar. The observed velocity dispersion of P3 is largely caused by blurred rotation and has a maximum value of s = 1183 c 201 km s super(-1). This is much larger than the dispersion s 250 km s super(-1) of the red stars along the same line of sight and is the largest integrated velocity dispersion observed in any galaxy. The rotation curve of P3 is symmetric around its center. It reaches an observed velocity of V = 618 c 81 km s super(-1) at radius 0.05 = 0.19 pc, where the observed velocity dispersion is s = 674 c 95 km s super(-1). The corresponding circular rotation velocity at this radius is 61700 km s super(-1). We therefore confirm earlier suggestions that the central dark object interpreted as a supermassive black hole is located in P3. Thin-disk and Schwarzschild models with intrinsic axial ratios b/a < 0.26 corresponding to inclinations between 55 and 58 match the P3 observations very well. Among these models, the best fit and the lowest black hole mass are obtained for a thin-disk model with sub(; ) = 1.4 x 10 super(8) M sub(z). Allowing P3 to have some intrinsic thickness and considering possible systematic errors, the 1 s confidence range becomes (1.1-2.3) x 10 super(8) M sub(z). The black hole mass determined from P3 is independent of but consistent with Peiris & Tremaine's mass estimate based on the eccentric disk model for P1+P2. It is 62 times larger than the prediction by the correlation between M sub(; ) and bulge velocity dispersion s sub(bulge). Taken together with other reliable black hole mass determinations in nearby galaxies, notably the Milky Way and M32, this strengthens the evidence that the M sub(; )-s sub(bulge) relation has significant intrinsic scatter, at least at low black hole masses. We show that any dark star cluster alternative to a black hole must have a half-mass radius <0.03 = 0.11 pc in order to match the observations. Based on this, M31 becomes the third galaxy (after NGC 4258 and our Galaxy) in which clusters of brown dwarf stars or dead stars can be excluded on astrophysical grounds.
Rate coefficients for the CH3 + CH3 reaction, over the temperature range 300–900 K, have been corrected for errors in the absorption coefficients used in the original publication ( Slagle et al., J. ...Phys. Chem. 1988, 92, 2455−2462 ). These corrections necessitated the development of a detailed model of the B̃2A1′ (3s)–X̃2A2″ transition in CH3 and its validation against both low temperature and high temperature experimental absorption cross sections. A master equation (ME) model was developed, using a local linearization of the second-order decay, which allows the use of standard matrix diagonalization methods for the determination of the rate coefficients for CH3 + CH3. The ME model utilized inverse Laplace transformation to link the microcanonical rate constants for dissociation of C2H6 to the limiting high pressure rate coefficient for association, k ∞(T); it was used to fit the experimental rate coefficients using the Levenberg–Marquardt algorithm to minimize χ2 calculated from the differences between experimental and calculated rate coefficients. Parameters for both k ∞(T) and for energy transfer ⟨ΔE⟩down(T) were varied and optimized in the fitting procedure. A wide range of experimental data were fitted, covering the temperature range 300–2000 K. A high pressure limit of k ∞(T) = 5.76 × 10–11(T/298 K)−0.34 cm3 molecule–1 s–1 was obtained, which agrees well with the best available theoretical expression.
Atomic layer deposition (ALD) is a method to grow thin metal oxide layers on a variety of materials for applications spanning from electronics to catalysis. Extending ALD to colloidally stable ...nanocrystals promises to combine the benefits of thin metal oxide coatings with the solution processability of the nanocrystals. However, challenges persist in applying this method, which relate to finding precursors that promote the growth of the metal oxide while preserving colloidal stability throughout the process. Herein, we introduce a colloidal ALD method to coat nanocrystals with amorphous metal oxide shells using metal and oxygen precursors that act as colloidal stabilizing ligands. Our scheme involves metal-amide precursors modified with solubilizing groups and oleic acid as the oxygen source. The growth of the oxide is self-limiting and proceeds in a layer-by-layer fashion. Our protocol is generalizable and intrinsically scalable. Potential applications in display, light detection, and catalysis are envisioned.
Global forest assessments use forest area as an indicator of biodiversity status, which may mask below-canopy pressures driving forest biodiversity loss and ‘empty forest’ syndrome. The status of ...forest biodiversity is important not only for species conservation but also because species loss can have consequences for forest health and carbon storage. We aimed to develop a global indicator of forest specialist vertebrate populations to improve assessments of forest biodiversity status. Using the Living Planet Index methodology, we developed a weighted composite Forest Specialist Index for the period 1970–2014. We then investigated potential correlates of forest vertebrate population change. We analysed the relationship between the average rate of change of forest vertebrate populations and satellite-derived tree cover trends, as well as other pressures. On average, forest vertebrate populations declined by 53% between 1970 and 2014. We found little evidence of a consistent global effect of tree cover change on forest vertebrate populations, but a significant negative effect of exploitation threat on forest specialists. In conclusion, we found that the forest area is a poor indicator of forest biodiversity status. For forest biodiversity to recover, conservation management needs to be informed by monitoring all threats to vertebrates, including those below the canopy.
ABSTRACT
The cool-core galaxy cluster RXJ1720.1+2638 hosts extended radio emission near the cluster core, known as a minihalo. The origin of this emission is still debated and one piece of the puzzle ...has been the question of whether the supermassive black hole in the brightest central galaxy is actively powering jets. Here, we present high-resolution e-MERLIN observations clearly indicating the presence of sub-kpc jets; this may have implications for the proposed origin of the minihalo emission, providing an ongoing source of relativistic electrons rather than a single burst sometime in the past, as previously assumed in simulations attempting to reproduce observational characteristics of minihalo-hosting systems.
Gene therapy strategies for congenital myopathies may require repeat administration of adeno-associated viral (AAV) vectors in response to several limitations inherent to the clinical design: 1) ...administration of doses below therapeutic efficacy in patients enrolled in early phase clinical trials; 2) progressive reduction of the therapeutic gene expression over time as a result of increasing muscle mass in patients treated at a young age; and 3) a possibly faster depletion of pathogenic myofibers in this patient population. Immune responses triggered by the first vector administration, and to subsequent ones, represent a major obstacle for successful gene transfer in young patient population. Anti-capsid and anti-transgene product related humoral and cell-mediated responses have been previously observed in all preclinical models and human subjects who received gene therapy or ERT treatment for congenital myopathies. Immune responses may result in reduced efficacy of the gene transfer over time and/or may preclude for the possibility of re-administration of the same vector. This study presents a case of Pompe patient dosed with an AAV1-GAA vector after receiving Rituximab and Sirolimus to modulate the immune responses. A key finding of this single subject case report is the observation that B-cell ablation with rituximab prior to AAV vector exposure results in non-responsiveness to both capsid and transgene, therefore allowing the possibility of repeat administration in the future. This observation is significant for future gene therapy studies and establishes a clinically relevant approach to blocking immune responses to AAV vectors.
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