Objectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade,... Show moreObjectives The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA).Methods Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) and Early Arthritis Clinic (EAC)) were analysed. Clinical data were collected up to 24 years. Hands and feet radiographs were scored according to the Sharp van der Heijde (SvdH) method. Latent class analysis was applied to determine the EA phenotypes at baseline. Each class received a label reflecting its most prominent features. Prognostic outcomes included Health Assessment Questionnaire (HAQ), Short Form 36 (SF36) and SvdH score. The association between class membership and outcomes over time was tested in multivariable models.Results In total, 390 (Reade), 798 (ESPOIR) and 3991 (EAC) patients were analysed separately. Two classes with symmetrical polyarthritis emerged; one of these labelled as autoimmune inflammatory polyarthritis (AIPA), had high likelihood of acute phase reactants (APR) elevation and autoantibody positivity, while the other (mild-inflammatory polyarthritis; MIPA) had not. A third class had oligoarthritis of upper limbs (OAUL) and could be subdivided into autoimmune OAUL and mild-inflammatory OAUL. A fifth class had oligoarthritis of lower limbs. The SvdH scores were worse in patients with APR/autoantibodies (AIPA) than in those without (MIPA). No clinically meaningful differences across classes in HAQ or SF36 over time were found.Conclusion Radiographic progression over time primarily occurs in EA patients with APR/autoantibodies. The absence of these markers, however, does not necessarily translate into better long-term function and quality of life. Clinicians should not only aim at preventing joint damage, but look beyond structural progression in order to further improve the lives of people with EA. Show less
Abstract Division of labor can evolve when social groups benefit from the functional specialization of its members. Recently, a novel means of coordinating the division of labor was found in the... Show moreAbstract Division of labor can evolve when social groups benefit from the functional specialization of its members. Recently, a novel means of coordinating the division of labor was found in the antibiotic-producing bacterium Streptomyces coelicolor, where specialized cells are generated through large-scale genomic re-organization. We investigate how the evolution of a genome architecture enables such mutation-driven division of labor, using a multiscale computational model of bacterial evolution. In this model, bacterial behavior—antibiotic production or replication—is determined by the structure and composition of their genome, which encodes antibiotics, growth-promoting genes, and fragile genomic loci that can induce chromosomal deletions. We find that a genomic organization evolves, which partitions growth-promoting genes and antibiotic-coding genes into distinct parts of the genome, separated by fragile genomic loci. Mutations caused by these fragile sites mostly delete growth-promoting genes, generating sterile, and antibiotic-producing mutants from weakly-producing progenitors, in agreement with experimental observations. This division of labor enhances the competition between colonies by promoting antibiotic diversity. These results show that genomic organization can co-evolve with genomic instabilities to enable reproductive division of labor. Show less
H2O2 is a bulk chemical used as "green" alternative in a variety of applications, but has an energy and waste intensive production method. The electrochemical O2 reduction to H2O2 is viable... Show moreH2O2 is a bulk chemical used as "green" alternative in a variety of applications, but has an energy and waste intensive production method. The electrochemical O2 reduction to H2O2 is viable alternative with examples of the direct production of up to 20% H2O2 solutions. In that respect, we found that the dinuclear complex Cu2(btmpa) (6,6'-bis[[bis(2-pyridylmethyl)amino]methyl]-2,2'-bipyridine) reduces O2 to H2O2 with a selectivity up to 90 % according to single linear sweep rotating ring disk electrode measurements. Microbalance experiments showed that complex reduction leads to surface adsorption thereby increasing the catalytic current. More importantly, we kept a high Faradaic efficiency for H2O2 between 60 and 70 % over the course of 2 h of amperometry by introducing high potential intervals to strip deposited copper (depCu). This is the first example of extensive studies into the long term electrochemical O2 to H2O2 reduction by a molecular complex which allowed to retain the high intrinsic selectivity of Cu2(btmpa) towards H2O2 production leading to relevant levels of H2O2. Show less
Jiang, L.; Dijk, B. van; Wu, L.; Clément, M.; Hofmann, J.P.; Tudor, V.; ... ; Schneider, G.F. 2022
Molecular complexes can be used as electrocatalysts for oxygen reduction, water oxidation, and/or hydrogen peroxide production. However, in situ degradation of these catalyst is a major issue. This... Show moreMolecular complexes can be used as electrocatalysts for oxygen reduction, water oxidation, and/or hydrogen peroxide production. However, in situ degradation of these catalyst is a major issue. This dissertations describes the analysis of degradation processes as well as the performance of various molecular electrocatalysts. In addition, complexes have been structurally modified to perform structure-activity studies that could to mechanistic insight. In addition, it is described how molecular catalysts can be beneficial to heterogeneous electrocatalysis as well. Show less
Smits, N.W.G.; Dijk, B. van; Bruin, I. de; Groeneveld, S.L.T.; Siegler, M.A.; Hetterscheid, D.G.H. 2020
To date, the copper complex with the tris(2-pyridylmethyl)amine (tmpa) ligand (Cu-tmpa) catalyzes the ORR with the highest reported turnover frequency (TOF) for any molecular copper catalyst. To... Show moreTo date, the copper complex with the tris(2-pyridylmethyl)amine (tmpa) ligand (Cu-tmpa) catalyzes the ORR with the highest reported turnover frequency (TOF) for any molecular copper catalyst. To gain insight into the importance of the tetradentate nature and high flexibility of the tmpa ligand for efficient four-electron ORR catalysis, the redox and electrocatalytic ORR behavior of the copper complexes of 2,2':6',2 ''-terpyridine (terpy) and bis(2-pyridylmethyl)amine (bmpa) (Cu-terpy and Cu-bmpa, respectively) were investigated in the present study. With a combination of cyclic voltammetry and rotating ring disk electrode measurements, we demonstrate that the presence of the terpy and bmpa ligands results in a decrease in catalytic ORR activity and an increase in Faradaic efficiency for H2O2 production. The lower catalytic activity is shown to be the result of a stabilization of the Cu-I state of the complex compared to the earlier reported Cu-tmpa catalyst. This stabilization is most likely caused by the lower electron donating character of the tridentate terpy and bmpa ligands compared to the tetradentate tmpa ligand. The Laviron plots of the redox behavior of Cu-terpy and Cu-bmpa indicated that the formation of the ORR active catalyst involves relatively slow electron transfer kinetics which is caused by the inability of Cu-terpy and Cu-bmpa to form the preferred tetrahedral coordination geometry for a CuI complex easily. Our study illustrates that both the tetradentate nature of the tmpa ligand and the ability of Cu-tmpa to form the preferred tetrahedral coordination geometry for a CuI complex are of utmost importance for ORR catalysis with very high catalytic rates. Show less
Cu electrodeposition in both underpotential and overpotential regimes on nanostructured MoS2 and WS2 prepared by plasma-enhanced atomic layer deposition has been studied in detail. A combination of... Show moreCu electrodeposition in both underpotential and overpotential regimes on nanostructured MoS2 and WS2 prepared by plasma-enhanced atomic layer deposition has been studied in detail. A combination of electrochemical methods, advanced characterization by X-ray absorption spectroscopy (XAS) as well as theoretical modelling were employed to reveal Cu adsorption modes on transition metal dichalcogenides (TMDs) from initial stages until bulk deposition. Since Cu UPD on TMDs has been used recently to evaluate the number of electrochemically active sites (NAS) for H2 evolution reaction, we evaluate and discuss here the implications of the Cu electrodeposition phenomena on nanostructured MoS2 and WS2 gauging the general applicability of the Cu UPD method for number of HER active sites determination in TMDs. Although an apparently better correlation of HER current density with Cu UPD charge than with double layer capacitance is found, the Cu UPD method cannot be used quantitatively because of the absence of a clear H UPD phenomenon on the studied nanostructured TMDs. This is in contrast to platinum group metal catalysts where H UPD and Cu UPD sites are strongly correlated. Show less
Objectives Healthcare professionals other than rheumatologists experience difficulties in detecting early inflammatory arthritis (IA) by joint examination. Self-reported symptoms are increasingly... Show moreObjectives Healthcare professionals other than rheumatologists experience difficulties in detecting early inflammatory arthritis (IA) by joint examination. Self-reported symptoms are increasingly considered as helpful and could be incorporated in online tools to assist healthcare professionals, but first their discriminative ability must be assessed. As part of this effort, we evaluated whether inquiring about functional impairments could aid early IA identification. Design Cross-sectional derivation and validation study. Setting Data from two Early Arthritis Recognition Clinics (EARC) in the Netherlands were studied, which are easy access outpatient rheumatology clinics intermediary between primary and secondary care for patients in whom general practitioners suspect but are unsure about IA presence. Participants Between 2010 and 2014, 997 patients consecutively visited the Leiden-EARC (derivation cohort). Patients consecutively visiting the Groningen EARC (2010-2014, n=506) and Leiden-EARC (2015-2018, n=557) served as validation cohorts. Primary and secondary outcome measures Physical functioning was assessed with the Health Assessment Questionnaire Disability-Index (HAQ); IA presence by physical joint examination by rheumatologists. HAQ questions were studied individually regarding discriminative ability for IA presence. For the best discriminating question, ORs and positive predictive values (PPVs) for IA presence were determined. Results IA was ascertained in 43% (derivation cohort), 53% and 35% (validation cohorts). In the derivation cohort, IA presence associated with higher mean HAQ scores (0.84 vs 0.73, p=0.003). One question on difficulties with dressing equalled discriminative ability of the total HAQ score. 'Difficulties with dressing' yielded ORs for IA presence of 1.8 (95% CI 1.4 to 2.4) in the derivation cohort; 2.0 (1.4 to 2.9) and 2.1 (1.5 to 3.1) in the validation cohorts. After adjustments for clinical characteristics these were 1.7 (1.3 to 2.3), 1.6 (1.1 to 2.5) and 1.9 (1.2 to 2.9). PPVs (probabilities of IA for positive answers) ranged 42%-60% and negative predictive values (probabilities of no IA for negative answers) ranged 57%-74%. Conclusions Patient-reported difficulties with dressing in patients with suspected IA associated with actual IA presence. Although further validation is required, for example, in primary care, this simple question could be of help in future early IA detection tools for healthcare professionals with limited experience in joint examination. Show less
Dijk, B. van; Hofmann, J.P.; Hetterscheid, D.G.H. 2018
Radicals produced by illumination or ionizing radiation are important in life sciences and chemistry. Reducing the rate of radical decay by recombination can be vital for maximizing the yield of... Show moreRadicals produced by illumination or ionizing radiation are important in life sciences and chemistry. Reducing the rate of radical decay by recombination can be vital for maximizing the yield of radical pair products, or to study reaction pathways. We propose a new method to reduce the probability for singlet-born radical pair recombination, based on the population of energetically isolated radical pair spin levels, and present an application to photoinduced radical pairs in photosynthetic reaction centers, for which we have achieved a 40-fold increase in the low temperature (23 K) radical pair lifetime. Show less
