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.

Interventions for enhancing return to work in individuals with a common mental illness: systematic review and meta-analysis of randomized controlled trials.

Common mental disorders (CMDs) are highly prevalent in the working population, and are associated with long-term sickness absence and disability. Workers on sick leave with CMDs would benefit from interventions that enable them to successfully return to work (RTW). However, the effectiveness of RTW interventions for workers with a CMD is not well studied. The objective of this review is to assess the effectiveness of existing workplace and clinical interventions that were aimed at enhancing RTW. A systematic review of studies of interventions for improving RTW in workers with a CMD was conducted. The main outcomes were proportion of RTW and sick-leave duration until RTW. Randomized controlled trials (RCTs) were identified from Medline/PubMed, PsycINFO, EMBASE, SocINDEX, and Human resource and management databases from January 1995 to 2016. Two authors independently selected studies, assessed risk of bias and extracted data. We pooled studies that we deemed sufficiently homogeneous in different comparison groups and assessed the overall quality of the evidence. We reviewed 2347 abstracts from which 136 full-text articles were reviewed and 16 RCTs were included in the analysis. Combined results from these studies suggested that the available interventions did not lead to improved RTW rates over the control group [pooled risk ratio 1.05, 95% confidence interval (CI) 0.97-1.12], but reduced the number of sick-leave days in the intervention group compared to the control group, with a mean difference of -13.38 days (95% CI -24.07 to -2.69).

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.).

Acoustic and microwave tests in a cylindrical cavity for acoustic gas thermometry at high temperature.

Relative primary acoustic gas thermometry (AGT) determines the ratios of thermodynamic temperatures from measured ratios of acoustic and microwave resonance frequencies in a gas-filled metal cavity on isotherms of interest. When measured in a cavity with known dimensions, the frequencies of acoustic resonances in a gas determine the speed of sound, which is a known function of the thermodynamic temperature T. Changes in the dimensions of the cavity are measured using the frequencies of the cavity's microwave resonances. We explored techniques and materials for AGT at high temperatures using a cylindrical cavity with remote acoustic transducers. We used gas-filled ducts as acoustic waveguides to transmit sound between the cavity at high temperatures and the acoustic transducers at room temperature. We measured non-degenerate acoustic modes in a cylindrical cavity in the range 295 K

Transitioning Youth into Adult Mental Health and Addiction Services: An Outcomes Evaluation of the Youth Transition Project.

The Youth Transition Project was designed to provide youth with mental health and addiction issues with individualized transitional care plans as they transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS). Over an 18-month period, a total of 127 (59.1%) youth were transitioned and seen by an AMHS provider, 41 (19.1%) remained on a waitlist for services and 47 (21.8%) canceled services. The average time to transition was 110 days (SD = 100). Youth exhibited a wide range of diagnoses; 100% of the population was identified as having serious psychiatric problems. Findings demonstrate that the Youth Transition Project has been successful in promoting continuity of care by transitioning youth seamlessly from youth to adult services. Inconsistencies in wait times and service delivery suggest that further model development is needed to enhance the long-term sustainability of the Youth Transition Project.

Two approaches for addressing electrochemical electrode arrays with reduced external connections.

Although patterning hundreds or thousands of electrochemical electrodes on lab-on-a-chip devices is straightforward and cost-effective using photolithography, easily making connections between hundreds of electrodes and external amplifiers remains a bottleneck. Here we describe two electrode addressing approaches using multiple fluid compartments that can potentially reduce the number of external connections by ~100-fold. The first approach enables all compartments on the device to be filled with solution at the same time, and then each fluid compartment is sequentially electrically activated to make the measurements. The second approach achieves lower measurement noise by sequentially filling recording chambers with solution. We propose an equivalent circuit to explain measurement noise in these recording configurations and demonstrate application of the approaches to measure quantal exocytosis from individual cells. A principle advantage of using these approaches is that they reduce the fraction of the microchip area that needs to be dedicated to making external connections and therefore reduces the cost per working electrode.

Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study.

Nilotinib (Tasigna) is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) who are newly diagnosed or intolerant of or resistant to imatinib. The 48-month follow-up data for patients with CML-CP treated with nilotinib after imatinib resistance or intolerance on an international phase II study were analyzed. Overall, 59% of patients achieved major cytogenetic response; 45% achieved complete cytogenetic response while on study. The estimated rate of overall survival (OS) and progression-free survival (PFS) at 48 months was 78% and 57%, respectively. Deeper levels of molecular responses at 3 and 6 months were highly positively correlated with long-term outcomes, including PFS and OS at 48 months. Of the 321 patients initially enrolled in the study, 98 (31%) were treated for at least 48 months. Discontinuations were primarily due to disease progression (30%) or adverse events (21%). Nilotinib is safe and effective for long-term use in responding patients with CML-CP who are intolerant of or resistant to imatinib. Further significant improvements in therapy are required for patients who are resistant or intolerant to imatinib.

Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase.

Nilotinib is a selective inhibitor of BCR-ABL approved for use in newly diagnosed and imatinib-resistant or -intolerant patients with chronic myeloid leukemia (CML) in chronic phase. In this study, 400 mg of nilotinib was administered twice daily to the patients with myeloid (MBP, n=105) or lymphoid blastic phase (LBP, n=31) CML. After a minimum follow-up of 24 months, major hematologic responses were observed in 60% (MBP) and 59% (LBP) of patients. Major cytogenetic responses (MCyR) were attained in 38% (MBP) and 52% (LBP) of patients; and complete cytogenetic responses in 30% and 32%, respectively. Median duration of MCyR was 10.8 (MBP) and 3.2 months (LBP). Median overall survival was 10.1 (MBP) and 7.9 (LBP) months with 12- and 24-month survival of 42% (MBP 44%, LBP 35%) and 27% (MBP 32%, LBP 10%), respectively. Twelve MBP patients and two LBP patients received subsequent stem cell transplantation. Myelosuppression was frequent, with grade 3/4 neutropenia, thrombocytopenia, and anemia in 68%, 63% and 47% of patients, respectively. Grade 3/4 hypophosphatemia, hyperbilirubinemia and lipase elevation were observed in 15%, 11% and 11% of patients, respectively. Nilotinib has significant efficacy in patients with BP CML, but given the limited long-term survival of these patients, novel agents are needed.

Tuberculous pericarditis: a diagnostic quandary.

Tuberculous pericarditis is uncommon in the Western world, and can prove a diagnostic quandary in that confirmation of the diagnosis and culture of mycobacteria can be difficult. We present a case of tuberculous pericarditis where endobronchial ultrasound-guided transbronchial needle biopsy of a pathological lymph node provided the diagnosis after other methods of investigation had proved futile.

An unusual infection in an injecting drug user.

Injecting drug users are prone to atypical infections. We present a case of septic thrombophlebitis secondary to Fusobacterium gonidiaformans infection in a heroin user, which demonstrates the frequently unusual nature of pathogens and presentations in this group of patients.

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.

Measuring secretion in chromaffin cells using electrophysiological and electrochemical methods.

Our present understanding of exocytosis of catecholamines has benefited tremendously from the arrival of single-cell electrochemical methods (amperometry and voltammetry), electrophysiological techniques (whole-cell and patch capacitance) and from the combination of both techniques (patch amperometry). In this brief review, we will outline the strengths and limitations of amperometric and electrophysiological methods and highlight the major contribution obtained with the use of these techniques in chromaffin cells.

Experience with low-dose valganciclovir prophylaxis in adult liver transplant recipients.

Valganciclovir (VGCV) is considered the agent of choice after organ transplant for cytomegalovirus (CMV) prophylaxis. The purpose of this retrospective study was to determine the effectiveness and safety of a low-dose regimen after liver transplant (OLT). Eighty-five patients who underwent OLT between August 2002 and August 2004 were included. All patient data for the first 12 months after transplant were collected. Patients received VGCV 450 mg once daily for 3 months posttransplant. CMV infection was based on detection of CMV virus or viral proteins in blood. CMV disease was defined by the presence of positive antigenemia/viremia and evidence of clinical symptoms and/or tissue findings. Patients were D+R+ (54%) and D-R+ (29%), D+R-(11%) and D-R-(6%). Overall, CMV infection and disease occurred in 13% (11/85). CMV infection and disease occurred in 7% and 6%, respectively. CMV infection and disease occurred in 44% (D+R-), 13% (D+R+), 4% (D-R+) patients. The mean time to onset of CMV infection and disease was 103 days (14 to 312 days). Overall, 82% of patients received antibody therapy. The most common adverse events associated with VGCV were leukopenia (16%), thrombocytopenia (4%), anemia (<1%), and neurotoxicity (<1%). Low-dose VGCV was not an effective means to prevent CMV infection in high-risk (D+R-) patients, especially those who received antibody induction. High-risk patients may require a high-dose regimen, such as 900 mg daily, and/or a longer period of prophylaxis, and/or reduction in the use of potent antibody treatments after liver transplant.

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

Naturally occurring Sarcocystis infection in domestic cats (Felis catus).

Equine protozoal myeloencephalitis is an important neurological disease of horses in the United States. Consequently, there is an active research effort to identify hosts associated with the primary causative agent, Sarcocystis neurona. The purpose of this study was to determine whether the domestic cat (Felis catus) is a natural host for S. neurona. Muscle sections from 50 primarily free-roaming domestic cats were examined for the presence of sarcocysts. Serum from cats in this group and another group of 50 free-roaming cats were evaluated for the presence of S. neurona antibody. Sarcocysts were found in five of 50 (10%) cats, and S. neurona antibody in five of 100 (5%) cats. Morphological, molecular (including ribosomal RNA genes), and biological characterisation of these sarcocysts showed that they were not S. neurona or S. neurona-like. Sarcocysts found in the cats were identified morphologically as Sarcocystis felis, a common parasite of wild felids. The life cycle of S. felis is not known, and prior to this study, no molecular marker for S. felis existed. Although cats were found to be infected with S. felis sarcocysts, serological data provided evidence of possible infection with S. neurona as well. Further work is needed to determine the role of the domestic cat in the life cycle of S. neurona.

Transcriptional profiling of human osteoblast differentiation.

Osteoblast differentiation is a key aspect of bone formation and remodeling. To further our understanding of the differentiation process, we have developed a collection of conditionally immortalized adult human osteoblast cell lines representing discrete stages of differentiation. To evaluate changes in gene expression associated with differentiation, polyA((+)) RNA from pre-osteoblasts, early and late osteoblasts, and pre-osteocytes was subjected to gene chip analysis using the Affymetrix Hu6800 chip in conjunction with an Affymetrix custom chip enriched in bone and cartilage cDNAs. Overall, the expression of 47 genes was found to change threefold or more on both chips between the pre-osteoblastic and pre-osteocytic stages of differentiation. Many of the observed differences, including down-regulation of collagen type I and collagen-processing enzymes, reflect expected patterns and support the relevance of our results. Other changes have not been reported and offer new insight into the osteoblast differentiation process. Thus, we observed regulation of factors controlling cell cycle and proliferation, reflecting decreased proliferation, and increased apoptosis in pre-osteocytic cells. Elements maintaining the cytoskeleton, extracellular matrix, and cell-cell adhesion also changed with differentiation reflecting profound alterations in cell architecture associated with the differentiation process. We also saw dramatic down-regulation of several components of complement and other immune response factors that may be involved in recruitment and differentiation of osteoclasts. The decrease in this group of genes may provide a mechanism for controlling bone remodeling of newly formed bone. Our screen also identified several signaling proteins that may control osteoblast differentiation. These include an orphan nuclear receptor DAX1 and a small ras-related GTPase associated with diabetes, both of which increased with increasing differentiation, as well as a high mobility group-box transcription factor, SOX4, that was down-regulated during differentiation. In summary, our study provides a comprehensive transcriptional profile of human osteoblast differentiation and identifies several genes of potential importance in controlling differentiation of osteoblasts.