Naar een metropolitaan bewustzijn

Sinds de introductie van de Metropoolregio Amsterdam staan de begrippen metropool en metropoolvorming opnieuw volop in de aandacht. De netwerkstad Noordvleugel moet uitgroeien tot volwaardige Europese metropool, aldus het ontwikkelingsbeeld Metropoolregio Amsterdam 2040. Maar wat is een metropool? En hoe maakbaar is deze? Metropolen zijn vaak lastig af te bakenen en zeer dynamisch, wat planningsinnovaties op dit niveau lastig maakt. Ervaringen in verschillende andere landen laten dan ook zien dat het ontstaan van een metropolitaan bewustzijn niet vanzelfsprekend i

The Prevalence of Titanium Dioxide Particles in Synovial Fluid Samples Drops after European Union Ban

Due to health concerns, the European Union has banned the use of titanium dioxide nanoparticles in consumables in February 2022, with a 6-month transitional period ending in August 2022. We studied the prevalence of titanium dioxide nanoparticles in synovial fluid samples during and after the transitional period. A total of 302 samples were collected as a consecutive series between 1 April 2022 and 15 June 2023 from patients visiting the department of rheumatology at VieCuri Medical Centre in Venlo, The Netherlands. The samples were primarily collected for diagnostic purposes and only clinical waste material was used for this study. From each sample, up to 40 μl of fluid was analysed with Raman spectroscopy for the presence of titanium dioxide particles. The trend in prevalence was calculated with a 3-month wide moving average. A total of 13 out of 302 samples (4.3%) contained titanium dioxide (TiO2). The prevalence of TiO2 decreased between the transitional period and the period after the ban (p = 0.0154, with a relative risk ratio of 4.9 (95% CI 1.35–17.74). There was no significant difference in patient characteristics between the TiO2 positive and the TiO2 negative group. These results are hinting towards a possible relationship between the EU-ban and the identified decrease in prevalence

Prospects for high-resolution microwave spectroscopy of methanol in a Stark-deflected molecular beam

Recently, the extremely sensitive torsion-rotation transitions in methanol have been used to set a tight constraint on a possible variation of the proton-to-electron mass ratio over cosmological time scales. In order to improve this constraint, laboratory data of increased accuracy will be required. Here, we explore the possibility for performing high-resolution spectroscopy on methanol in a Stark-deflected molecular beam. We have calculated the Stark shift of the lower rotational levels in the ground torsion-vibrational state of CH3OH and CD3OH molecules, and have used this to simulate trajectories through a typical molecular beam resonance setup. Furthermore, we have determined the efficiency of non-resonant multi-photon ionization of methanol molecules using a femtosecond laser pulse. The described setup is in principle suited to measure microwave transitions in CH3OH at an accuracy below 10^{-8}

Network theory approach for data evaluation in the dynamic force spectroscopy of biomolecular interactions

Investigations of molecular bonds between single molecules and molecular complexes by the dynamic force spectroscopy are subject to large fluctuations at nanoscale and possible other aspecific binding, which mask the experimental output. Big efforts are devoted to develop methods for effective selection of the relevant experimental data, before taking the quantitative analysis of bond parameters. Here we present a methodology which is based on the application of graph theory. The force-distance curves corresponding to repeated pulling events are mapped onto their correlation network (mathematical graph). On these graphs the groups of similar curves appear as topological modules, which are identified using the spectral analysis of graphs. We demonstrate the approach by analyzing a large ensemble of the force-distance curves measured on: ssDNA-ssDNA, peptide-RNA (system from HIV1), and peptide-Au surface. Within our data sets the methodology systematically separates subgroups of curves which are related to different intermolecular interactions and to spatial arrangements in which the molecules are brought together and/or pulling speeds. This demonstrates the sensitivity of the method to the spatial degrees of freedom, suggesting potential applications in the case of large molecular complexes and situations with multiple binding sites

Real-life results of urate-driven pharmacotherapy with three urate lowering drugs in gout:allopurinol, febuxostat and benzbromarone

Aim:This study aims to assess outcomes of gout patients from the treat to target (T2T) perspective at 6 months and 12 months while using urate lowering therapy (ULT): allopurinol, febuxostat, and/or benzbromarone.Methods:All gout patients visiting the Rheumatology department between 2015 to 2021 were identified from the digital hospital system. The diagnosis of gout was based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2015 classification criteria. Patient outcomes were predefined intention to treat (ITT) categories: category 1: patients with serum uric acid (sUA) ≤ 0.360 mmol/L (ACR target for gout); category 2: patients with sUA ≤ 0.300 mmol/L (ACR/EULAR target for severe gout); category 3: patients with sUA > 0.360 (failure to meet ACR target).Results:Gout diagnoses were present in 1,186 patients: 986 (83.1%) males and 200 (16.9%) females. A follow-visit at 6 months was present in 76.9% (n = 856) out of 1,113 patients reaching sUA < 0.36 mmol/L, but 257 (23%) failed to reach the 0.36 mmol/L target. At 12 months, a follow-up visit was available in 792 (71.1%) patients, and from these, 710 (90%) had reached sUA < 0.36 mmol/L target. The use of benzbromarone was a strong predictor of reaching the sUA < 0.30 mmol/L target: odds ratio (OR) 3.2, 95% confidence interval (CI) (1.735, 6.017) at 6 months. Diabetic patients had the highest proportion of not reaching the target: 18%. Male patients needed higher dosages of allopurinol to reach the sUA target at 6 months compared to female patients.Conclusions:This is a large study on a T2T approach based in a real-life clinical setting. Only 42% reached the sUA target at 6 months with allopurinol 300 mg quaque die (QD) monotherapy. About 77% of gout patients reach the predefined sUA target of 0.36 mmol/L at 6 months with the availability of three ULTs. There is still a significant unmet need in gout as many patients failed to achieve predefined sUA targets

Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate–Associated Arthritis

Objective: We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)–associated arthritis (CPPD). Methods: This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. Results: The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3–94.2), specificity 99.1% (95% CI 97.5–99.8), positive likelihood ratio 100.33 (95% CI 32.3–311.3), negative likelihood ratio 0.14 (95% CI 0.07–0.28), positive predictive value 93.5% (95% CI 82.2–97.8), negative predictive value 98.0% (95% CI 82.2–97.8), and accuracy 97.5% (95% CI 95.5–98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. Conclusion: iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.</p