Introduction: Depressive and anxiety disorders are common mental disorders ranking among the leading causes of global disease burden. Not all clients currently benefit from therapy and clients are... Show moreIntroduction: Depressive and anxiety disorders are common mental disorders ranking among the leading causes of global disease burden. Not all clients currently benefit from therapy and clients are looking for modern ways of therapy. Online psychotherapy is a promising option for better meeting clients’ needs. Recently, a new psychotherapy concept has emerged that combines videoconferencing sessions with support through a mobile application. The latter allows for ecological momentary assessments and interventions, facilitates communication between patients and therapists in between sessions through chat, and allows for incorporating feedbackinformed treatment principles. Material and methods: The study was a retrospective observational matched cohort study, comparing online psychotherapy with Therapy As Usual (TAU) for clients with depressive or anxiety disorders. Data were obtained via questionnaires, which are part of standard clinical care. Primary outcomes included general mental functioning, and symptoms of depression and anxiety. Secondary outcomes were efficiency, client satisfaction, and therapy costs. Primary endpoints were analyzed using linear mixed models analysis, with an interaction term between time and group. Secondary outcomes were analyzed using linear regression. Results: Larger improvements were observed in the online compared to the TAU group for general mental functioning and depressive disorder (i.e., General mental functioning: B = -8.50, 95 CI: − 15.01 − − 1.97, p = 0.011; Depressive disorder: B = − 3.66, 95 % CI: − 5.79 – -1.54p < 0.01). No significant differences in change over time between the two groups were observed for anxiety disorder (B = -3.64, 95 % CI: (− 13.10 – 5.82) p = 0.447). The total number of sessions was significantly higher in the online psychotherapy group than in TAU (B = 3.71, p < 0.01), although clients were matched on treatment time in weeks. Treatment session duration in minutes was comparable across the groups. Discussion: Online psychotherapy with app support showed to be a promising alternative to TAU for depressive and anxiety disorders. More research is needed to evaluate the effectiveness, cost-effectiveness and client satisfaction of online psychotherapy compared to TAU, such as randomized controlled trials or studies multiple baseline series designs, and in-depth qualitative research. Show less
BACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS\nIntranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry.... Show moreBACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS\nIntranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry. Immunogenicity of intranasal vaccination can be improved through the use of adjuvants. Bacteria-like particles derived fromLactococcus lactishave the potential to serve as a vaccine adjuvant.This clinical study investigated the safety, reactogenicity and immunogenicity of intranasal seasonal influenza vaccine adjuvanted with gram-positive matrix particles (FluGEM®).\nThis was a first-in-human, randomized, double-blind, controlled, dose-escalation study performed at the Centre for Human Drug Research (CHDR), the Netherlands. Participants aged 18-49 were randomized in a 3:1 ratio to receive FluGem® in ascending doses (two-dose regimens) together with a standard trivalent inactivated influenza vaccine or unadjuvanted TIV only. Primary outcomes were safety and tolerability. Secondary outcomes were serum hemagglutination inhibition (HI) antibody titers and mucosal IgA. The most immunogenic dose was used in an additionalelderly cohort (>65 years).\nNinty participants were included. Intranasal FluGem®was safe and well tolerated. The majority of adverse events were mild (97.4 %) with (un)solicited adverse events comparable across all dose levels and control groups. All groups showed geometric mean increases ≥ 2.5-fold. Seroconversion (≥40 % participants) was achieved at both day 21 (single-dose) and 42 (two-dose) for the 1.25 mg dose and on day 42 (two-dose only) for the 2.5 mg dose. Highest geometric mean IgA increases were observed in the 1.25 mg group on day 21. Immunogenicity was less pronounced in elderly.\nIntranasal vaccination of FluGEM®was safe and tolerable in healthy adult volunteers aged 18-49 years and 65 and older. Highest immunogenicity was observed for 1.25 mg and 2.5 mg doses (compared to 5 mg) suggesting a potential non-linear dose-response relationship.More research is needed to further investigate the capabilities of bacteria-like peptides as adjuvants. Show less
This thesis first provides a grammar sketch of Teke-Kukuya which is a Bantu language spoken in the Republic of Congo, covering the topics on its segmental phonology and prosodic system, noun... Show moreThis thesis first provides a grammar sketch of Teke-Kukuya which is a Bantu language spoken in the Republic of Congo, covering the topics on its segmental phonology and prosodic system, noun classes and noun phrases, verbal morphology and TAM conjugations, as well as some syntactic issues based on newly collected data. The second part of the thesis investigates the interaction between syntax and information structure in this language. The author discusses word order variation and expressions of information structure with particular interests in a dedicated immediate-before-verb (IBV) focus position in this language. Since the IBV focus construction shares many grammatical properties with clefts, both segmentally and tonally, the author makes the hypothesis that diachronically the IBV focus strategy originates from a basic cleft, and it has been grammaticalised towards a monoclausal focus construction. The thesis also gives a synchronic analysis on the structural representation of the IBV focus construction, discussing the subject agreement asymmetry in subject/non-subject relatives and the associated class 1 subject marking alternation in the IBV focus construction. Show less
Hydrogen fuel cells are expected to be pivotal in the energetic transition towards renewable energy sources such as solar and wind power. However, their industrial scalability is severely hindered... Show moreHydrogen fuel cells are expected to be pivotal in the energetic transition towards renewable energy sources such as solar and wind power. However, their industrial scalability is severely hindered by the high cost and degradation rate of platinum catalysts, one of their key components. Addressing this challenge necessitates developing better catalysts, which requires a better fundamental understanding of their reactivity and degradation mechanism. In this thesis, we investigate the (in)stability of model platinum surfaces submerged in liquid and under applied voltage, thus simulating the operational conditions of fuel cells. For this we use a home-build Electrochemical Scanning Tunneling Microscope (EC-STM), which allows us to observe, in real time, the surface structure at the atomic scale. Our findings elucidate the origin of the platinum surface roughening that takes place upon voltage cycling. Moreover, we demonstrate that closely-spaced atomic steps are prone to bunch together, resulting in steps with multi-atomic height. This structural change has a significant effect on the catalyst reactivity, as we explain in detail. Overall, this dissertation contributes to a deeper fundamental understanding of the surface processes that drive platinum surface restructuring as well as their implications for reactivity. Show less
Interventional oncology has rapidly developed into a significant pillar in the treatment of liver cancer. Thermal ablation is an example of an interventional oncology treatment, in which a needle... Show moreInterventional oncology has rapidly developed into a significant pillar in the treatment of liver cancer. Thermal ablation is an example of an interventional oncology treatment, in which a needle can be directly inserted into the tumor from outside the body. The tip of this needle can become extremely hot through the use of radiofrequency or microwaves, effectively burning the tumor from the inside out. Transarterial therapies are other interventional oncology treatments that can be administered through the arteries of the affected part of the liver. Small microspheres containing radioactive material or chemotherapy block the blood supply to the tumor and deliver the treatment locally.Part one of this thesis describes the research into ablation margin confirmation. Standardized pre- and post-ablation CT scans were registered and used to quantify the obtained ablation margin. This workflow was first tested in the IAMCOMPLETE study. Potentially, this software tool could identify patients at risk for local recurrent cancer.Part two of this thesis studies combined treatment regimens of early stage HCC. The HORA EST HCC study was the first clinical trial to combine thermal ablation with radioembolization. Hyperaemia around the ablation zone was found to cause radiation dose accumulation in the tissue susceptible to local residual tumor after thermal ablation.In part three of this thesis, the long-term affect after radioembolization was studied. Show less
There is accumulating evidence for an increase in severe global drought events. In particular, Europe experienced several severe droughts in 2003, 2015, and 2018 (unprecedented in the past 2,110... Show moreThere is accumulating evidence for an increase in severe global drought events. In particular, Europe experienced several severe droughts in 2003, 2015, and 2018 (unprecedented in the past 2,110 years). Such droughts have caused serious and far-reaching impacts on terrestrial ecosystems. As droughts are predicted to become more prolonged and intense across wide regions in the coming decades, the risks to the human system as a result of the disturbed ecosystems worldwide will increase. To mitigate these risks, it is critical to prioritize the most vulnerable ecosystems and intervene on time. Thus, the understanding of ecosystem responses and their vulnerability to intensive drought needs to be developed. This thesis reveals European-wide ecosystem vulnerability based on ecosystem responses. With more frequent and severe droughts in the future, a wide range of ecosystems will become more vulnerable and may even collapse due to high mortality. This thesis provides several suggestions for timely early warning and intervention possibilities for vulnerable ecosystems. Moreover, this thesis demonstrates the potential of remote sensing in monitoring ecosystem responses. Combining remote sensing for early and comprehensive monitoring of ecosystems will provide new possibilities and critical information for future drought prevention and management. Show less
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
In 2018, the nationwide action program Solid Start was launched by the Dutch Ministry of Health, Welfare and Sport, aiming to ensure the best possible start for all children during the first... Show moreIn 2018, the nationwide action program Solid Start was launched by the Dutch Ministry of Health, Welfare and Sport, aiming to ensure the best possible start for all children during the first thousand days of life. The 'first thousand days' refer to the period from conception to a child's second birthday, which lays the foundation for health and wellbeing in later life and across generations. The main objective of this thesis was to provide insight into the adoption of the Dutch nationwide action program Solid Start, thereby focusing on monitoring and cross-sectoral collaboration. Throughout our studies, we learned that monitoring vulnerability in early life and monitoring the action program Solid Start at local level requires a consideration of both risk and protective factors spanning across multiple sectors. This underscores the relevancy for preventive programs that connect the medical and social sector, and it implies that monitoring requires cross-sectoral longitudinal data and indicators. For future practice and policy, we advise to create a long-term perspective, integrate the action program Solid Start into everyday practice and stimulate learning processes at different levels. Despite opportunities for improvement, this thesis implies a solid start for the Dutch first thousand days-approach. Show less
In light of climate change, it is crucial to determine whether plant species can adapt to future climates to avoid extinction. Plants adapt to various conditions by altering their functional traits... Show moreIn light of climate change, it is crucial to determine whether plant species can adapt to future climates to avoid extinction. Plants adapt to various conditions by altering their functional traits, such as leaf size or photosynthetic rate. Some traits appear linked and vary together between species, suggesting resource management strategies of plants. Traits can also vary within species, known as intraspecific trait variation (ITV), and its extent varies between species. Our understanding of how and why these traits vary within species is limited.This dissertation uses newly compiled global databases of species' ITV and genetic adaptation rates. We investigate whether trait-trait relationships between species also occur within species, confirming these as true plant strategies. We then explore the drivers of components of ITV: phenotypic plasticity, allowing plants to change in response to the environment, and genetic adaptation, involving inherited changes. Each offers different benefits for species adapting to changing conditions. By combining them, we can better understand plant species' adaptive capacity. Finally, we evaluate whether plants with different growth forms and from different biomes differ in their adaptive capacity to climate change.Our results provide new insights into plant strategies and have important implications for vegetation modelling and conservation efforts. Show less
This thesis investigates the interaction between syntax and information structure (IS) in Tunen, a Bantu language spoken in Cameroon by approximately 70,000-100,000 people. Tunen has previously... Show moreThis thesis investigates the interaction between syntax and information structure (IS) in Tunen, a Bantu language spoken in Cameroon by approximately 70,000-100,000 people. Tunen has previously been noted to be unusual for a Bantu language in several respects, being the only one of the 550-some Bantu languages reported to have subject-object-verb (SOV) rather than subject-verb-object (SVO) basic word order. As previous work suggested that Tunen's unusual syntax relates to IS, this thesis serves to test this relationship. The principal data source comes from fieldwork conducted by the author in Ndikiniméki/Yaoundé, Cameroon, with supplementary evidence from secondary sources and remote elicitation. The results indicate that Tunen syntax shows less influence from IS than expected from previous work on the language and the surrounding languages. Instead, Tunen's basic word order is shown to be consistent across discourse contexts, clause types, and object types. Alongside discussion of the SOV word order, the thesis investigates IS expression and the syntax of a typologically-unusual discontinuous DP construction, which is shown to be found across information-structural contexts. A first formal analysis of Tunen syntax is provided within the framework of generative syntax, and the thesis also includes an updated grammatical overview of the language and sample texts. 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
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
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
