Nocebo effects are adverse treatment outcomes that cannot be attributed to active treatment components. A common example is the experiencing of side effects after reading the side effect... Show moreNocebo effects are adverse treatment outcomes that cannot be attributed to active treatment components. A common example is the experiencing of side effects after reading the side effect description on a medication leaflet. Nocebo hyperalgesia, i.e., increased pain sensitivity due to nocebo effects, can be acquired via learning in both healthy and clinical populations, and has a large social and economic impact on healthcare. In the current dissertation, we investigated the experimental learning mechanisms behind the acquisition and recovery of nocebo hyperalgesia in healthy individuals and in patients with fibromyalgia, and the potential differences between groups. Additionally, we investigated the predictors of nocebo hyperalgesia acquisition and recovery to identify individuals who are more susceptible to these effects. Lastly, we stepped outside of the lab-settings and in an electronic diary study, examined the role of (experimentally-induced) nocebo hyperalgesia in daily pain progression of patients with fibromyalgia. The current dissertation offers insights for better understanding the expectancy and learning mechanisms behind nocebo hyperalgesia in individuals with and without chronic pain. These can be useful for the future design of personalised learning-based interventions for targeting nocebo effects on pain. Show less
A Josephson junction is a device where a thin insulating barrier or a nanostructure is placed between two superconducting leads. Such a junction is essential to superconducting qubits that store... Show moreA Josephson junction is a device where a thin insulating barrier or a nanostructure is placed between two superconducting leads. Such a junction is essential to superconducting qubits that store quantum information due to its anharmonic spectrum. Therefore, understanding the physics of these junctions is crucial for predictions of the qubit's main qualities, such as the dephasing and relaxation time. Most modern superconducting qubits use Josephson junctions with an insulating barrier (tunneling junction). One of this thesis aims is to explore other possibilities that may allow for better properties of the qubit. Show less
This study examines a single English language usage problem, number agreement in the variants of the species noun phrase ; e.g. 'these kinds of errors' vs. 'these kind of errors' vs. 'errors of... Show moreThis study examines a single English language usage problem, number agreement in the variants of the species noun phrase ; e.g. 'these kinds of errors' vs. 'these kind of errors' vs. 'errors of this kind' from three perspectives: those of linguists, prescriptivists and the general public. The study, framed by the descriptions given in modern reference grammars and theoretical analyses (the linguists), is conducted within the historical perspective of the advice given in usage guides published between 1770 and 2010 and beyond (the prescriptivists). The general public is represented in an online attitude survey of the variant forms, and by an analysis of a corpus of un-copy-edited academic writing that was compiled specifically for this study. The main findings are (i) that there is a great deal of harmony between the views of the three groups studied, and that, on the basis of these analyses, the popular view of 'descriptive' linguists in conflict with 'prescriptive' usage guides is not justified; and (ii) that the innovative use of multiple contextualised examples in the attitude survey contributes to the suggestion of - a cline of acceptability - on the part of the general public, rather than a simple - acceptable- vs. - unacceptable stance- . Show less
This thesis describes the development of a reference standard for urinary tract infection (UTI) research. It also provides cut-off values for pyuria and novel urine biomarkers to more accurately... Show moreThis thesis describes the development of a reference standard for urinary tract infection (UTI) research. It also provides cut-off values for pyuria and novel urine biomarkers to more accurately diagnose UTI in older women. Finally, this thesis investigates intravesical aminoglycoside instillations and faecal microbiota replacement as strategies to prevent urinary tract infections in patients with recurrent UTI. Show less
Damage to the endothelial glycocalyx leads to endothelial dysfunction and microvascular changes, which can progress to the development cardiovascular complications. In type 2 diabetes, the... Show moreDamage to the endothelial glycocalyx leads to endothelial dysfunction and microvascular changes, which can progress to the development cardiovascular complications. In type 2 diabetes, the pathogenic diabetic milieu induces structural changes in the endothelial glycocalyx. In this thesis, we investigate if microvascular changes can be detected and used as a diagnostic marker in individuals at risk of developing cardiovascular disease. Secondly, we show that urinary MCP-1 and HPSE-1 levels are correlated with the urinary albumin creatinine ratio in a multi-ethnic cohort of individuals with type 2 diabetes. Higher urinary MCP-1 levels can be found in individuals from Moroccan and South-Asian Surinamese descent. Lastly, we show a fasting mimicking diet is effective to reduce Hba1c end BMI in South-Asian Surinamese patients with diabetes, but did not improve the microvascular health. In the diabetic glomerulus, the loss of capillaries was prevented but increased oxidative stress was found. A supplement with glycocalyx mimetic did improve the microvascular health in South-Asian individuals and showed to preserve glomerular endothelial coverage in the experimental study. In this thesis, we show that the endothelial glycocalyx can be used as a diagnostic marker for vascular health and can be used as a therapeutic target in type 2 diabetes. Show less
This dissertation examines the digitisation and automation of Chinese courts from 2013 until 2022. Occurring in parallel with a multitude of other judicial reforms, this dissertation argues that... Show moreThis dissertation examines the digitisation and automation of Chinese courts from 2013 until 2022. Occurring in parallel with a multitude of other judicial reforms, this dissertation argues that Marxist-Leninist ideological conceptions of the role of law and courts in governance facilitate the rapid embrace of automated technologies. They shape the adoption and deployment of these technologies as well as the consequences. The principal ideological conviction that drives smart court reform (SCR) is that the technologies of automation will turn justice administration into a real science, and that science will make adjudication fairer and more efficient. The digitisation and automation of courts reveal that there exists a pervasive conviction among China's intellectual and ruling elite that governance and justice need to be scientific, to be legitimate and fair. This conviction guides the digitisation and automation of all domains in China's political-legal system.In addition, this dissertation argues that SCR has contradictory goals that seem difficult to reconcile. However, because of ideological conceptions, these goals are not seen as contradictory within the Chinese political-legal system itself. Show less
Evidence grows that standard toxicity testing might underestimate the environmental risk of neurotoxic insecticides. Behavioural endpoints such as locomotion and mobility have been suggested as... Show moreEvidence grows that standard toxicity testing might underestimate the environmental risk of neurotoxic insecticides. Behavioural endpoints such as locomotion and mobility have been suggested as sensitive and ecologically relevant additions to the standard tested endpoints. Possible interactive effects of chemicals and additional stressors are typically overlooked in standardised testing. Therefore, we aimed to investigate how concurrent exposure to environmental stressors (increased temperature and predation cues) and a nicotinic acetylcholine receptor (nAChR)-modulating insecticide (‘sulfoxaflor’) impact Chironomus riparius across a range of conventional and non-conventional endpoints. We used a multifactorial experimental design encompassing three stressors, sulfoxaflor (2.0-110 µg/L), predation risk (presence/absence of predatory cues), and elevated temperature (20°C and 23°C), yielding a total of 24 distinct treatment conditions. Additional stressors did not change the sensitivity of C. riparius to sulfoxaflor. To assess potential additive effects, we applied an Independent Action (IA) model to predict the impact on eight endpoints, including conventional endpoints (growth, survival, total emergence, and emergence time) and less conventional endpoints (the size of the adults, swimming abilities and exploration behaviour). For the conventional endpoints, observed effects were either lower than expected or well-predicted by the IA model. In contrast, we found greater than predicted effects of predation cues and temperature in combination with sulfoxaflor on adult size, larval exploration, and swimming behaviour. However, in contrast to the non-conventional endpoints, no conventional endpoints detected interactive effects of the neurotoxic insecticide and the environmental stressors. Acknowledging these interactions, increasing ecological context of ecotoxicological test systems may, therefore, advance environmental risk analysis and interpretation as the safe environmental concentrations of neurotoxic insecticides depend on the context of both the test organism and its environment. Show less
The current use of chemicals puts pressure on human and ecological health. Based on the Aarhus Convention, citizens have the right to have access to information on substances in their local... Show moreThe current use of chemicals puts pressure on human and ecological health. Based on the Aarhus Convention, citizens have the right to have access to information on substances in their local environment. Providing this information is a major challenge, especially considering complex mixtures, as the current substance-by-substance risk assessment may not adequately address the risk of co-exposure to multiple substances. Here, we provide an overview of the currently available indicators in the Netherlands to explore current scientific possibilities to indicate the impacts of complex chemical mixtures in the environment on human health and ecology at the local scale. This is limited to impact estimates on freshwater species for 701 substances, impact estimates of four metals on soil organisms, and impacts on human health for particulate matter (PM10) and nitrogen dioxide (NO2) in air. The main limiting factors in developing and expanding these indicators to cover more compartments and substances are the availability of emission and concentration data of substances and dose-response relationships at the population (human health) or community (ecology) level. As ways forward, we propose; 1) developing cumulative assessment groups (CAGs) for substances on the European Pollutant Transfer and Release Register and Water Framework Directive substance lists, to enable the development of mixture indicators based on mixture risk assessment and concentration addition principles; 2) to gain insight into local mixtures by also applying these CAGs to emission data, which is available for soil and air for more substances than concentrations data; 3) the application of analytical non-target screening methods as well as effect-based methods for whole-mixture assessment. Show less
Weird times call for weird narratives. The language of reason and facts or technological fixes do not adequately help people make sense of a disorienting present and unpredictable future, under the... Show moreWeird times call for weird narratives. The language of reason and facts or technological fixes do not adequately help people make sense of a disorienting present and unpredictable future, under the looming specter of environmental catastrophe. In the search for alternative responses to this condition, in this article (in Dutch) I turn to the ways in which speculative fiction, and weird fiction particularly, can help us navigate our ‘postnormal’ realities in the 21st century. On the occasion of the publication of Kate Marshall’s study Novels by Aliens (2023), I discuss Marshall’s book and reflect on the ways in which monsters, nonhuman scales and perspectives, and ‘weirded’ variants of realism can play, in Marshall’s words, a key role “in the conceptual work of the present.” Show less
Deze uitspraak is een annotatie waard omdat het de eerste uitspraak is waarin de Afdeling bestuursrechtspraak van de Raad van State beoordeelt of een bestuursorgaan het openbaar maken van... Show moreDeze uitspraak is een annotatie waard omdat het de eerste uitspraak is waarin de Afdeling bestuursrechtspraak van de Raad van State beoordeelt of een bestuursorgaan het openbaar maken van informatie op grond van de Wet open overheid (Woo) mocht weigeren vanwege de zogenaamde i-grond. Deze uitzonderingsgrond is een relatieve uitzonderingsgrond. Het bepaalt dat het openbaar maken van informatie achterwege blijft voor zover het belang daarvan niet opweegt tegen het belang van het goed functioneren van de Staat, andere publiekrechtelijke lichamen of bestuursorganen. Deze uitzonderingsgrond is nieuw ten opzichte van de Wob en sinds de inwerkingtreding van de Woo is de vrees geuit dat deze grond een ‘duizenddingendoekje’ zou worden voor bestuursorganen om openbaarmaking te weigeren. Jurisprudentie van de Afdeling over deze grond is daarom van groot belang om de kaders van deze nieuwe uitzonderingsgrond duidelijk te krijgen. Uit de uitspraak blijkt (kort samengevat) dat (i) tijdsverloop in acht moet worden genomen bij het bepalen of het goed functioneren in het geding is; en (ii) een belangenafweging op het niveau van een document(onderdeel) moet plaatsvinden, tenzij sprake is van een crisis. Show less
Computer tomography (CT)-guided percutaneous core biopsies are currently the gold standard in diagnostic procedures for patients with bone lesions of unknown kind. CT-guided biopsies can lead to... Show moreComputer tomography (CT)-guided percutaneous core biopsies are currently the gold standard in diagnostic procedures for patients with bone lesions of unknown kind. CT-guided biopsies can lead to misdiagnosis or repetition of biopsies in case of small or heterogeneous lesions. We hypothesize that molecular image guidance could be used to optimize the biopsy strategy, by supporting the detection of heterogeneous lesions or lesions without radiographic substrate. To evaluate this hypothesis, we investigated if and how the addition of 2-deoxy-2-18F-fluoro-D-glucose-positron emission tomography (18F-FDG-PET)/CT could augment routine CT-guided bone biopsies. To this end, 106 patients who underwent a CT-guided bone biopsy between April 2019 and April 2020, obtained from either a vertebral or peripheral bone, were included. Patients were divided into 2 groups: 36 patients received an 18F-FDG-PET/CT scan prior to their CT-guided bone biopsy (PET group), while 70 patients only had a morphological CT scan (CT group). Histopathology was used to categorize biopsies into five subgroups (inconclusive, benign, malignant or infectious disease, or normal tissue). In the PET group, the number of conclusive biopsies was significantly higher compared to the CT group (N = 33/36 (92%) versus N = 53/70 (76%); p < 0.05). Furthermore, the number of first-try biopsies was lower in the PET group compared to the CT group (1.9 vs. 2.54, p = 0.051). In conclusion, 18F-FDG-PET/CT imaging significantly increased the success rate of first-try CT-guided bone biopsies by showing less inconclusive biopsies and misdiagnosis. Show less
Background: Clinical and echocardiographic results of valve repair for mitral regurgitation in the setting of atrial fibrillation are poorly studied. Methods: Between January 2008 and December 2020... Show moreBackground: Clinical and echocardiographic results of valve repair for mitral regurgitation in the setting of atrial fibrillation are poorly studied. Methods: Between January 2008 and December 2020, 89 patients underwent valve repair for mitral regurgitation in the setting of atrial fibrillation. Clinical and echocardiographic follow-up data were collected and studied. The primary composite endpoint consisted of all-cause mortality or hospitalization for heart failure. Results: Valve repair with true-sized annuloplasty was performed in 83 (93 %) and restrictive annuloplasty in 6 (7 %) patients. Early mortality occurred in 3 (3 %) and residual mitral regurgitation in 1 (1 %) patient. During a median follow-up of 5.4 years (interquartile range 3.4–9.5), 25 patients died, 6 due to end-stage heart failure. Ten patients were hospitalized for heart failure. The estimated event-free survival rate at 10 years was 48.2 % (95 % CI 33.5 %–62.9 %). Recurrent mitral regurgitation was observed in 14 patients and most often caused by leaflet tethering. When analyzed as a time-dependent variable, recurrent regurgitation was related to the occurrence of the primary endpoint (hazard ratio 3.192, 95 % CI 1.219–8.359, p = 0.018). On exploratory sub-analyses, no recurrent regurgitation was observed after restrictive annuloplasty or in patients with paroxysmal atrial fibrillation. Moreover, recurrent regurgitation was observed more often when signs of left ventricular impairment were present preoperatively. Conclusions: Despite good initial results, recurrent regurgitation was a frequent observation after valve repair for mitral regurgitation in atrial fibrillation and had an effect on heart failure related morbidity and mortality. Refinements in the timing of surgery and surgical technique might help improve outcomes. Show less
The environmental impact of traded plastic waste hinges on how it is treated. Existing studies often use domestic or scenario-based recycling rates for imported plastic waste, which is problematic... Show moreThe environmental impact of traded plastic waste hinges on how it is treated. Existing studies often use domestic or scenario-based recycling rates for imported plastic waste, which is problematic due to differences in recyclability and the fact that importers pay for it. We estimate the minimum required recycling rate (RRR) needed to break even financially by analysing import prices, recycling costs, and the value of recycled plastics across 22 leading importing countries and four plastic waste types during 2013–2022. Here we show that at least 63% of imported plastic waste must be recycled, surpassing the average domestic recycling rate of 23% by 40 percentage points. This discrepancy suggests that recycled plastics volumes from the global North-to-South trade may be underestimated. The country-specific RRR provided could enhance research and policy efforts to better quantify and mitigate the environmental impact of plastic waste trade. Show less
Bilsen, M.P.; Conroy, S.P.; Schneeberger, C.; Platteel, T. N.; Nieuwkoop, C. van; Mody, L.; ... ; Lambregts, M.M.C. 2024
The absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and therapeutic studies. This... Show moreThe absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and therapeutic studies. This omission hinders the accumulation of evidence for a disease that imposes a substantial burden on patients and society, particularly in an era of increasing antimicrobial resistance. We did a three-round Delphi study involving an international, multidisciplinary panel of UTI experts (n=46) and achieved a high degree of consensus (94%) on the final reference standard. New-onset dysuria, urinary frequency, and urinary urgency were considered major symptoms, and non-specific symptoms in older patients were not deemed indicative of UTI. The reference standard distinguishes between UTI with and without systemic involvement, abandoning the term complicated UTI. Moreover, different levels of pyuria were incorporated in the reference standard, encouraging quantification of pyuria in studies done in all health-care settings. The traditional bacteriuria threshold (10⁵ colony-forming units per mL) was lowered to 10⁴ colony-forming units per mL. This new reference standard can be used for UTI research across many patient populations and has the potential to increase homogeneity between studies. Show less
Todtenhaupt, P.; Kuipers, T.B.; Dijkstra, K.L.; Voortman, L.M.; Franken, L.A.; Spekman, J.A.; ... ; Meeren, L.E. van der 2024
The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the... Show moreThe human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell–cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development. Show less
Morwani-Mangnani, J.; Rodriguez-Girondo, M.; Singh-Povel, C.; Verlaan, S.; Beekman, M.; Slagboom, P.E. 2024
Background: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing... Show moreBackground: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing research, the broader significance of how muscle health is affected by the intricate interplay of lifestyle factors simultaneously during aging needs more exploration. This study aims to examine how nutrition, physical activity, and sleep impact on FFM and handgrip strength in middle-aged men and women, facilitating future personalized recommendations for preserving muscle health. Methods: The cross-sectional analysis of the UK Biobank involved 45,984 individuals (54 % women) aged 40–70 years with a complete dataset. Multiple linear regression explored determinants of FFM and handgrip strength, considering traditional, socio-demographics, medication use and smoking as covariates, with sex and age (younger and older than 55 years) stratifications. Results: In older men and women, higher physical activity beneficially affect both FFM (respectively В = 3.36 × 10− 3 , p-value = 1.66 × 10− 3 ; В = 2.52 × 10− 3 , p-value = 3.57 × 10− 4 ) and handgrip strength (В = 6.05 × 10− 3 , p-value = 7.99 × 10− 5 , В = 8.98 × 10− 3 , p-value = 2.95 × 10− 15). Similar results were found in fiber intake for FFM in older men and women (respectively B = 3.00 × 10− 2 , p-value = 2.76 × 10− 5 ; B = 2.68 × 10− 2 , p-value = 1.78 × 10− 9 ) and handgrip strength (В = 3.27 × 10− 2 , p-value = 1.40 × 10− 3 ; В = 3.12 × 10− 2 , p-value = 1.34 × 10− 5 ). Other lifestyle factors influence FFM and handgrip strength differently. Key determinants influencing handgrip strength included higher protein intake, lower water intake, higher alcohol intake, and extended sleep duration whereas mainly higher water intake is associated with higher FFM. Conclusions: In both men and women, the main factors associated with FFM and handgrip strength are physical activity and fiber intake, which may underlie a connection between gut and muscle health. Given the observed complexity of muscle health in the age and sex strata, further longitudinal research is needed to provide personalized lifestyle recommendations. Show less
Background: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers’ knowledge and risk perception of rabies and risk behaviour during travel can help... Show moreBackground: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers’ knowledge and risk perception of rabies and risk behaviour during travel can help identify knowledge gaps and improve pre-travel risk education. Methods: Cohort study in Dutch adult travellers, using two surveys: one before travel to assess knowledge and perception of rabies, and one after return to identify risk behaviour during travel. Results: The pre-travel and post-travel survey were completed by 301 and 276 participants, respectively. 222 participants had travelled to a high-risk rabies-endemic country. 21.6 % of the participants scored their rabies knowledge as poor. Some participants were unaware cats or bats can transmit rabies (26.6 % and 13.6 %, respectively), or that post-exposure prophylaxis (PEP) is required for certain exposures such as skin abrasions without bleeding or licks on damaged skin (35.5 % and 18.9 %, respectively), while 27.9 % of participants did not know PEP needs to be administered within one day. 115 participants (51.8 %) reported any form of contact with any animal during travel. Two participants reported animal exposure, of which one took adequate PEP measures. Risk factors for animal contact abroad were regularly touching cats or dogs at home or abroad, longer travel duration, having pets during childhood and being an animal lover. Conclusions: Pre-travel rabies risk education currently does not meet travellers’ needs, which is reflected in knowledge gaps and engagement in risk behaviour during travel. During pre-travel health advice, avoiding animal contact abroad should be emphasized, and additional education is required about indications for PEP. Show less
Objectives: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. Materials and Methods: High... Show moreObjectives: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. Materials and Methods: High-risk individuals with a CDKN2A/p16 germline pathogenic variant participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve was computed. Results: In total, 220 HRIs were included between 2000 and 2019. Median age was 61 (interquartile range. 53–71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (odds ratio, 1.21; 95% confidence interval, 0.39–3.78) and 4 of 5 PDAC cases seemed to have NOD within 3 months before diagnosis. Furthermore, NOD did not differentiate between HRIs with and without PDAC (area under the curve, 0.54; 95% confidence interval, 0.46–0.61). Conclusions: In this study, we found no added value for longitudinal glucose monitoring in CDKN2A pathogenic variant carriers participating in an imaging-based pancreatic cancer surveillance program. Show less
