Analgesics use and ESRD in younger age: a case-control study

<p>Abstract</p> <p>Background</p> <p>An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design.</p> <p>Methods</p> <p>We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed.</p> <p>Results</p> <p>The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3^rdtertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 – 1.0) and 1.0 (0.8 – 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a significantly decreased risk, a tiny subgroup of extreme users with over 3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg lifetime use recommended by the regulatory advisors showed an impressive excess of other conditions than analgesics triggering the evolution of ESRD in cases compared with controls.</p> <p>Conclusion</p> <p>We found no clinically meaningful evidence for an increased risk of ESRD associated with use of phenacetin-free analgesics in single or combined formulation. The apparent risk increase shown in a small subgroup with extreme lifetime dose of analgesics is most likely an indirect, non-causal association. This hypothesis, however, cannot be confirmed or refuted within our case-control study. Overall, our results lend support to the mounting evidence that phenacetin-free analgesics do not induce ESRD and that the notion of "analgesic nephropathy" needs to be re-evaluated.</p

Outlook for inverse design in nanophotonics

Recent advancements in computational inverse design have begun to reshape the landscape of structures and techniques available to nanophotonics. Here, we outline a cross section of key developments at the intersection of these two fields: moving from a recap of foundational results to motivation of emerging applications in nonlinear, topological, near-field and on-chip optics.Comment: 13 pages, 6 figure

Decoding the dopamine signal in Macaque prefrontal cortex: a simulation study using the Cx3Dp simulator

Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake

Estimating the seismicity of Venus by scaling Earth's seismicity

With the selection of multiple missions to Venus by NASA and ESA planned to launch in the coming decade, we will greatly improve our understanding of Venus as a planet. However, the selected missions cannot tell us anything about the seismicity on Venus, which is a crucial observable to constrain the tectonic activity and geodynamic regime of the planet, and its interior structure. Here, we provide new, preliminary estimates of Venus’ global annual seismic budget and the expected frequency of venusquakes per year. We obtain this estimate by scaling the seismicity of the Earth recorded in the CMT catalogue. We test different potential scaling factors based on e.g., the difference in mass, radius, potential seismogenic volume, etc. We also sort the earthquakes into their respective tectonic settings, which allows us to exclude irrelevant tectonic settings present on Earth, but most likely not on Venus from our analysis. This enables us to present a range of potential seismic budgets and venusquake frequencies per tectonic setting on Venus. This then provides a new estimate of the potential amount of seismicity on Venus. However, it is uncertain how valid this simple scaling approach is from Earth to Venus. Indeed, previous attempts of scaling the volcanism of Earth to Venus (Byrne & Krishnamoorthy, 2022; Van Zelst, 2022) resulted in numbers that aligned with independent estimates, but are still unconstrained and hard to verify until the announced missions fly. Therefore, in order to provide a more robust and holistic view of Venus’ anticipated seismicity, estimates using various different, independent methods should ideally be considered. To provide exactly that, we set up the ISSI team ‘Seismicity on Venus: Prediction & Detection’. This is an interdisciplinary team of experts in seismology, geology, and geodynamics. Together we aim to assess the seismic activity on Venus from a theoretical and instrumental perspective. In addition to presenting our preliminary seismicity estimates from scaling Earth to Venus, we therefore also use this contribution to briefly introduce the team and its goals and present the preliminary findings from our first, week-long, dedicated in-person meeting aimed at further characterising Venus’ seismicity