Proton pump inhibitor use and progression to major adverse renal events: a competing risk analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD). AIM: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD. DESIGN: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 1 January 2006 until 31 December 2016. METHODS: We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end-stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis. RESULTS: There were 3824 patients with CKD included in the analyses of whom 1195 were prescribed a PPI. The PPI group was younger (64.8 vs. 67.0 years, P < 0.001), with lower estimated glomerular filtration rate (eGFR) (30 vs. 35 ml/min, P < 0.001) and more proteinuria (64 vs. 48 mg/mmol, P < 0.001). PPI use was associated with progression to MARE on multivariable adjustment (hazard ratio 1.13 [95% confidence interval 1.02-1.25], P = 0.021). Other factors significantly associated with progression to MARE were higher systolic blood pressure, lower eGFR, greater proteinuria, congestive cardiac failure and diabetes. Hypomagnesaemia was more common in the PPI group (39.5 vs. 18.9%, P < 0.001). CONCLUSION: PPI use was associated with progression to MARE, but not death in patients with CKD after adjusting for factors known to predict declining renal function, including lower eGFR, proteinuria and comorbidities. A prospective cohort study is required to validate these findings.

Determination of the Boltzmann constant with cylindrical acoustic gas thermometry: new and previous results combined.

We report a new determination of the Boltzmann constant kB using a cylindrical acoustic gas thermometer. We determined the length of the copper cavity from measurements of its microwave resonance frequencies. This contrasts with our previous work (Zhang et al 2011 Int. J. Thermophys.32 1297, Lin et al 2013 Metrologia50 417, Feng et al 2015 Metrologia52 S343) that determined the length of a different cavity using two-color optical interferometry. In this new study, the half-widths of the acoustic resonances are closer to their theoretical values than in our previous work. Despite significant changes in resonator design and the way in which the cylinder length is determined, the value of kB is substantially unchanged. We combined this result with our four previous results to calculate a global weighted mean of our kB determinations. The calculation follows CODATA's method (Mohr and Taylor 2000 Rev. Mod. Phys. 72 351) for obtaining the weighted mean value of kB that accounts for the correlations among the measured quantities in this work and in our four previous determinations of kB. The weighted mean k̂B is 1.380 6484(28) × 10-23 J K-1 with the relative standard uncertainty of 2.0 × 10-6. The corresponding value of the universal gas constant is 8.314 459(17) J K-1 mol-1 with the relative standard uncertainty of 2.0 × 10-6.

Detecting leaks in gas-filled pressure vessels using acoustic resonances.

We demonstrate that a leak from a large, unthermostatted pressure vessel into ambient air can be detected an order of magnitude more effectively by measuring the time dependence of the ratio p/f(2) than by measuring the ratio p/T. Here f is the resonance frequency of an acoustic mode of the gas inside the pressure vessel, p is the pressure of the gas, and T is the kelvin temperature measured at one point in the gas. In general, the resonance frequencies are determined by a mode-dependent, weighted average of the square of the speed-of-sound throughout the volume of the gas. However, the weighting usually has a weak dependence on likely temperature gradients in the gas inside a large pressure vessel. Using the ratio p/f(2), we measured a gas leak (dM/dt)/M ≈ - 1.3 × 10(-5) h(-1) = - 0.11 yr(-1) from a 300-liter pressure vessel filled with argon at 450 kPa that was exposed to sunshine-driven temperature and pressure fluctuations as large as (dT/dt)/T ≈ (dp/dt)/p ≈ 5 × 10(-2) h(-1) using a 24-hour data record. This leak could not be detected in a 72-hour record of p/T. (Here M is the mass of the gas in the vessel and t is the time.).

Standard photoacoustic spectrometer: model and validation using O2 A-band spectra.

We model and measure the absolute response of an intensity-modulated photoacoustic spectrometer comprising a 10 cm long resonator and having a Q-factor of approximately 30. We present a detailed theoretical analysis of the system and predict its response as a function of gas properties, resonance frequency, and sample energy transfer relaxation rates. We use a low-power continuous wave laser to probe O(2) A-band absorption transitions using atmospheric, humidified air as the sample gas to calibrate the system. This approach provides a convenient and well-characterized method for calibrating the absolute response of the system provided that water-vapor-mediated relaxation effects are properly taken into account. We show that for photoacoustic spectroscopy (PAS) of the O(2) A-band, the maximum conversion efficiency of absorbed photon energy to acoustic energy is approximately 40% and is limited by finite collision-induced relaxation rates between the two lowest-lying excited electronic states of O(2). PAS also shows great potential for high-resolution line shape measurements: calculated and experimental values for the PAS system response differ by about 1%.

Perturbations From Ducts on the Modes of Acoustic Thermometers.

We examine the perturbations of the modes of an acoustic thermometer caused by circular ducts used either for gas flow or as acoustic waveguides coupled to remote transducers. We calculate the acoustic admittance of circular ducts using a model based on transmission line theory. The admittance is used to calculate the perturbations to the resonance frequencies and half-widths of the modes of spherical and cylindrical acoustic resonators as functions of the duct's radius, length, and the locations of the transducers along the duct's length. To verify the model, we measured the complex acoustic admittances of a series of circular tubes as a function of length between 200 Hz and 10 kHz using a three-port acoustic coupler. The absolute magnitude of the specific acoustic admittance is approximately one. For a 1.4 mm inside-diameter, 1.4 m long tube, the root mean square difference between the measured and modeled specific admittances (both real and imaginary parts) over this frequency range was 0.018. We conclude by presenting design considerations for ducts connected to acoustic thermometers.

Bulk viscosity, thermoacoustic boundary layers, and adsorption near the critical point of xenon.

We present an improved model for the dissipation and dispersion in an acoustic resonator filled with xenon near its critical temperature Tc. We test the model with acoustic measurements in stirred xenon that have a temperature resolution of (T - Tc)/Tc approximately 7 x 10(-6). The model includes the frequency-dependent bulk viscosity calculated numerically from renormalization-group theory and it includes critical-point adsorption. Because the density of adsorbed xenon exceeds the critical density, the bulk viscosity's effect on surface dissipation is reduced, thereby improving the agreement between theory and experiment.

Bulk viscosity of stirred xenon near the critical point.

We deduce the thermophysical properties of near-critical xenon from measurements of the frequencies and half-widths of the acoustic resonances of xenon maintained at its critical density in centimeter-sized cavities. In the reduced temperature range 1 x 10-3<(T-Tc)/Tc<7 x 10 (-6), we measured the resonance frequency and quality factor (Q) for each of six modes spanning a factor of 27 in frequency. As Tc was approached, the frequencies decreased by a factor of 2.2 and the Q's decreased by as much as a factor of 140. Remarkably, these results are predicted (within +/-2% of the frequency and within a factor of 1.4 of Q) by a model for the resonator and a model for the frequency-dependent bulk viscosity zeta(omega) that uses no empirically determined parameters. The resonator model is based on a theory of acoustics in near-critical fluids developed by Gillis, Shinder, and Moldover [Phys. Rev. E 70, 021201 (2004)]. In addition to describing the present low-frequency data (from 120 Hz to 7.5 kHz), the model for zeta(omega) is consistent with ultrasonic (0.4--7 MHz) velocity and attenuation data from the literature. However, the model predicts a peak in the temperature dependence of the dissipation in the boundary layer that we did not detect. This suggests that the model overestimates the effect of the bulk viscosity on the thermal boundary layer. In this work, the acoustic cavities were heated from below to stir the xenon, thereby reducing the density stratification resulting from Earth's gravity. The stirring reduced the apparent equilibration time from several hours to a few minutes, and it reduced the effective temperature resolution from 60 mK to approximately 2 mK, which corresponds to (T-Tc)/Tc approximately =7 x 10(-6).

Thermoacoustic boundary layers near the liquid-vapor critical point.

We measure and calculate the sound attenuation within thermoacoustic boundary layers between solid surfaces and xenon at its critical density rhoc as the reduced temperature tau identical with (T- Tc)/Tc approaches zero. (Tc is the critical temperature.) Using the known thermophysical properties of xenon, we predict that the attenuation at the boundary first increases approximately as tau(-0.6) and then saturates when the effusivity of the xenon exceeds that of the solid. [The effusivity is epsilon identical with (rhoCPlambdaT)(1/2), where CP is the isobaric specific heat and lambdaT is the thermal conductivity.] The model correctly predicts (+/-1.0%) the quality factors Q of resonances measured in a stainless steel resonator (epsilon(ss) =6400 kg K(-1) s(-5/2)); it also predicts the observed increase of the Q, by up to a factor of 8, when the resonator is coated with a polymer (epsilon(pr) =370 kg K(-1) s(-5/2)). The test data span the frequency range 0.1

Effects of nucleotide substitutions within the T-loop of precursor tRNAs on interaction with ATP/CTP:tRNA nucleotidyltransferases from Escherichia coli and yeast.

Recognition of tRNA and tRNA-like substrates by the enzyme ATP/CTP:tRNA nucleotidyltransferase requires chemically intact nucleotides within the T-loop, especially at positions 57 and 58, which are invariant purines among naturally occurring tRNAs. To test the effects of base substitutions at these positions, which are distant from the site of catalysis, we synthesized mutant tRNA(Glu) molecules. These in vitro-synthesized RNAs also contained an extra 33 bases at the 5' end and lacked post-transcriptionally modified bases. The precursor tRNAs were used as substrates for nucleotidyltransferases from Escherichia coli and yeast. Substitution of cytidines at either position 57 or 58 had dramatic inhibitory effects on recognition by both enzymes, including raising the apparent Km and lowering the apparent Vmax.; substitution of an adenosine at position 57 or a uridine at position 58 inhibited the reaction only slightly by comparison. Our results demonstrate that the identities of nucleotides at positions 57 and 58 are relevant to recognition by nucleotidyltransferase, and that a purine is required at position 57. The extra bases at the 5' end and the lack of post-transcriptionally modified bases did not substantially inhibit interaction with the enzyme, as judged by the wild-type precursor tRNA(Glu) acting as an effective substrate for both enzymes in the presence of equal concentrations of appropriate tRNA substrates isolated from E. coli.