Urban areas are characterised by the presence of sensory pollutants, such as anthropogenic noise and artificial light at night (ALAN). Animals can quickly adapt to novel environmental conditions by adjusting their behaviour, which is proximately regulated by endocrine systems. While endocrine responses to sensory pollution have been widely reported, this has not often been linked to changes in behaviour, hampering the understanding of adaptiveness of endocrine responses. Our aim was, therefore, to investigate the effects of urbanisation, specifically urban noise and light pollution, on hormone levels in male urban and forest túngara frogs (Engystomops pustulosus), a species with reported population divergence in behaviour in response to urbanisation. We quantified testosterone and corticosterone release rates in the field and in the lab before and after exposure to urban noise and/or light. We show that urban and forest frogs differ in their endocrine phenotypes under field as well as lab conditions. Moreover, in urban frogs exposure to urban noise and light led, respectively, to an increase in testosterone and decrease in corticosterone, whereas in forest frogs sensory pollutants did not elicit any endo-crine response. Our results show that urbanisation, specifically noise and light pollution, can modulate hormone levels in urban and forest populations differentially. The observed endocrine responses are consistent with the observed behavioural changes in urban frogs, providing a proximate explanation for the presumably adaptive behavioural changes in response to urbanisation.
Beta‐blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age‐related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta‐blockers are associated with an increased risk of falls in older beta‐blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta‐blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B‐PROOF cohort. The associations between the beta‐blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11–2.16], p = .01). No association was found for nonselective beta‐blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta‐blockers users. This might be caused by a decreased β1‐selectivity in high plasma concentrations. In the future, beta‐blocker concentrations could potentially help clinicians estimate fall risk in older beta‐blockers users and personalize treatment.
Lymnaeid snails are simultaneous hermaphrodites that have a worldwide distribution, inhabiting freshwater areas from almost all continents ranging from tropical to arctic regions and from sea level to very high altitudes. In this chapter, we review the reproductive anatomy, behavioral and physiological traits, and mating strategies associated with increased survival and invasiveness of lymnaeids across different ecosystems around the globe. We also discuss the biotic and abiotic factors that can affect mating systems in this family, and how they have expanded their geographical range by natural, as well as human-mediated ways, likely promoting the spread of infectious diseases. Finally, we discuss why we believe that lymnaeids are suitable model organisms for studying mechanisms and processes involved in the ecology and evolution of mating systems and biological invasions.
Background Whether the degree of inflammation (and its resolution) and neurodegeneration after treatment initiation predicts disease progression in multiple sclerosis (MS) remains unclear. Objectives To assess the predictive value of magnetic resonance imaging (MRI)-derived brain and lesion volume (LV) changes in years 1 and 2 of treatment for disease progression. Methods Patients receiving early interferon beta-1a treatment in REFLEX/REFLEXION ( N = 262) were included. Predictive regression models included new/enlarging LV (positive activity), disappearing/shrinking LV (negative activity), and global/central atrophy during years 1 and 2. Results Faster global atrophy and/or pseudo-atrophy and positive lesion activity in years 1 and 2 related to an increased probability and faster conversion to clinically definite multiple sclerosis (CDMS). Negative lesion activity in year 1 and slower central atrophy in year 2 were predictive of confirmed disability progression (9-Hole Peg Test). Positive lesion activity in year 2 was predictive of faster global atrophy, while positive lesion activity in years 1 and 2 was predictive of faster central atrophy. Conclusions A higher degree of global atrophy and/or pseudo-atrophy in year 1 was predictive of CDMS. Positive lesion activity in any year was related to CDMS and neurodegeneration. Disability was related to negative lesion activity in year 1 and slower central atrophy in year 2.
Background Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. Methods Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). ResultsAbuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17–5.67) and neglect for BD (OR 2.69, 95% CI 2.09–3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55–3.01) and suicide attempts (OR 2.16, 95% CI 1.55–3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02–1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08–2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01–0.24). Conclusions Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.
A critical step in photocatalytic water dissociation is the hole-mediated oxidation reaction. Molecular-level insights into the mechanism of this complex reaction under realistic conditions with high temporal resolution are highly desirable. Here, we use femtosecond time-resolved, surface-specific vibrational sum frequency generation spectroscopy to study the photo-induced reaction directly at the interface of the photocatalyst TiO2 in contact with liquid water at room temperature. Thanks to the inherent surface specificity of the spectroscopic method, we can follow the reaction of solely the interfacial water molecules directly at the interface at timescales on which the reaction takes place. Following the generation of holes at the surface immediately after photoexcitation of the catalyst with UV light, water dissociation occurs on a sub-20 ps timescale. The reaction mechanism is similar at pH 3 and 11. In both cases, we observe the conversion of H2O into Ti-OH groups and the deprotonation of pre-existing Ti-OH groups. This study provides unique experimental insights into the early steps of the photo-induced dissociation processes at the photocatalyst-water interface, relevant to the design of improved photocatalysts.
INTRODUCTION China has the world's largest number of older adults with cognitive impairment (CI). We aimed to examine secular trends in the prevalence of CI in China from 2002 to 2018. METHODS Generalized estimating equations (GEE) was used to assess changes in CI trend in 44,154 individuals (72,027 observations) aged 65 to 105 years old. RESULTS The prevalence of CI increased from 2002 to 2008 and then decreased until 2018. The age‐standardized prevalence increased from 25.7% in 2002, 26.1% in 2005, to 28.2% in 2008, then decreased to 26.0% in 2011, 25.3% in 2014, and 24.9% in 2018. Females and those ≥ 80 years old had greater CI prevalence. DISCUSSION The prevalence of CI showed an inverted U shape from early 2000s to late 2010s with a peak in 2008. Follow‐up studies are needed to confirm the decreasing trend after 2008 and examine the contributing factors and underlying mechanisms of this trend. Highlights Generalized estimating equations (GEE) were used to assess trends of changes in cognitive impairment (CI). CI prevalence in China increased from 2002 to 2008 and then decreased until 2018. Females and those ≥ 80 years old had greater CI prevalence. Stroke, diabetes, and cigarette smoking were risk factors for CI.
How does your own body affect your research? How do we deal with unpleasant moments of being called out, misread, ignored or approached by other courtroom attendees during fieldwork? And how do these moments differ, if we investigate powerful institutions (the court, the police, the judge) vs. marginalised objects (the defendant on dock or their families and friends, co-present in the audience)? By drawing down on field research on anti-terrorism-financing trials in Germany and the Netherlands and by bringing into light our own positionality and objectives at stake, we offer some learning from our own fieldwork experiences and how to circumvent risk and turbulences at stake, by entering court spaces, especially those of special public interest, wherein Islamophobic stereotypes, gender-rendered assumptions and police-based information on war scenes and multiple forms of individual contributions herein come into play, which have enables certain modes of proliferation in combats scenes in Syria and Iraq, but also influence discourses on migration and anti-Muslim-resentments back home in Europe.
The physical climate storyline (PCS) approach is increasingly recognized by the physical climate research community as a tool to produce and communicate decision‐relevant climate risk information. While PCS is generally understood as a single concept, different varieties of the approach are applied according to the aims and purposes of the PCS and the scientists that build them. To unpack this diversity of detail, this article gives an overview of key practices and assumptions of the PCS approach as developed by physical climate scientists, as well as their ties to similar approaches developed by the broader climate risk and adaptation research community. We first examine varieties of PCSs according to the length of the causal chain they explore, and the type of evidence used. We then describe how they incorporate counterfactual elements and the temporal perspective. Finally, we examine how value judgments are implicitly or explicitly included in the aims and construction of PCSs. We conclude the discussion by suggesting that the PCS approach can further mature in the way it incorporates the narrative element, in the way it incorporates value judgments, and in the way that the evidence chosen to build PCSs constrains what is considered plausible. This article is categorized under: Assessing Impacts of Climate Change > Scenario Development and Application Climate, History, Society, Culture > Technological Aspects and Ideas Paleoclimates and Current Trends > Modern Climate Change
Background To estimate the perceived value of additional testing with amyloid-PET in Euros in healthy participants acting as analogue patients with mild cognitive impairment (MCI). Methods One thousand four hundred thirty-one healthy participants acting as analogue MCI patients (mean age 65 ± 8, 929 (75%) female) were recruited via the Dutch Brain Research Registry. Participants were asked to identify with a presented case (video vignette) of an MCI patient and asked whether they would prefer additional diagnostic testing with amyloid PET in this situation. If yes, respondents were asked how much they would be willing to pay for additional diagnostic testing. Monetary value was elicited via a bidding game in which participants were randomized over three conditions: (A) additional testing results in better patient management, (B) Same as condition A and a delay in institutionalization of 3 months, and (C) same as A and a delay in institutionalization of 6 months. Participants who were not willing to take a test were compared with participants who were willing to take a test using logit models. The highest monetary value per condition was analyzed using random-parameter mixed models. Results The vast majority of participants acting as analogue MCI patients (87% (n = 1238)) preferred additional testing with amyloid PET. Participants who were not interested were more often female (OR = 1.61 95% CI [1.09–2.40]) and expressed fewer worries to get AD (OR = 0.64 [0.47–0.87]). The median “a priori” (i.e., before randomization) monetary value of additional diagnostic testing was €1500 (IQR 500–1500). If an additional amyloid PET resulted in better patient management (not further specified; condition A), participants were willing to pay a median price of €2000 (IQR = 1000–3500). Participants were willing to pay significantly more than condition A (better patient management) if amyloid-PET testing additionally resulted in a delay in institutionalization of 3 months (€530 [255–805] on top of €2000, condition B) or 6 months (€596 [187–1005] on top of €2000, condition C). Conclusions Members of the general population acting as MCI patients are willing to pay a substantial amount of money for amyloid-PET and this increases when diagnostic testing leads to better patient management and the prospect to live longer at home.
Introduction Medical case vignettes play a crucial role in medical education, yet they often fail to authentically represent diverse patients. Moreover, these vignettes tend to oversimplify the complex relationship between patient characteristics and medical conditions, leading to biased and potentially harmful perspectives among students. Displaying aspects of patient diversity, such as ethnicity, in written cases proves challenging. Additionally, creating these cases places a significant burden on teachers in terms of labor and time. Our objective is to explore the potential of AI‐assisted computer‐generated clinical cases to expedite case creation and enhance diversity, along with AI‐generated patient photographs for more lifelike portrayal. Methods In this study, we employed chatGPT (OpenAI, GPT 3.5) to develop diverse and inclusive medical case vignettes. We evaluated various approaches and identified a set of eight consecutive prompts that can be readily customized to accommodate local contexts and specific assignments. To enhance visual representation, we utilized Adobe Firefly beta for image generation. Results Using the described prompts, we consistently generated cases for various assignments, producing sets of 30 cases at a time. We ensured the inclusion of mandatory checks and formatting, completing the process within approximately 60 minutes per set. Discussion Our approach significantly accelerated case creation and improved diversity, though prioritizing maximum diversity compromised representativeness to some extent. While the optimized prompts are easily reusable, the process itself demands computer skills not all educators possess. To address this, we aim to share all created patients as Open Educational Resources (OER), empowering educators to create cases independently.
In Alzheimer’s disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology. The Liver X receptor (LXR) family, consisting of LXRα and LXRβ, was reported to inhibit angiogenesis and particularly LXRα was shown to secure BBB stability, suggesting a major role in vascular function. In this study, we unravel the regulatory mechanism exerted by LXRα to preserve BBB integrity in human brain endothelial cells (BECs) and investigate its role during pathological conditions. We report that LXRα ensures BECs identity via constitutive inhibition of the transcription factor SNAI2. Accordingly, deletion of brain endothelial LXRα is associated with impaired DLL4-NOTCH signalling, a critical signalling pathway involved in vessel sprouting. A similar response was observed when BECs were exposed to hypoxia, with concomitant LXRα decrease and SNAI2 increase. In support of our cell-based observations, we report a general increase in vascular SNAI2 in the occipital cortex of AD patients with and without capCAA. Importantly, SNAI2 strongly associated with vascular amyloid-beta deposition and angiopoietin-like 4, a marker for hypoxia. In hypoxic capCAA vessels, the expression of LXRα may decrease leading to an increased expression of SNAI2, and consequently BECs de-differentiation and sprouting. Our findings indicate that LXRα is essential for BECs identity, thereby securing BBB stability and preventing aberrant angiogenesis. These results uncover a novel molecular pathway essential for BBB identity and vascular homeostasis providing new insights on the vascular pathology affecting AD patients.
Background We developed Street Temptations (ST) as an add-on intervention to increase the treatment responsivity of adolescents with disruptive behavior problems. ST’s primary aim is to improve adolescents’ mentalizing abilities in order to help them engage in and benefit from psychotherapy. Additionally, virtual reality (VR) is used to work in a more visual, less verbal, fashion. Objective By recapping the lessons learned while developing ST so far, we aim to design the following study on ST. Furthermore, we aim to enhance the development and study of new health care interventions in clinical practice, together with adolescents as their end users. Methods We followed an iterative co-creation process to develop a prototype of ST, in collaboration with adolescents and professionals from a secured residential facility in Amsterdam, the Netherlands. The prototype was tested during a pilot phase, involving 2 test runs, in which 4 adolescents and 4 professionals participated. Qualitative data were collected through interviews with the adolescents and by conducting a group interview with the professionals, in order to gain first insights into ST’s usability, feasibility, and its added value to clinical practice. In between the first and second test runs, the prototype was enhanced. On the basis of the complete pilot phase, we reflected on the future development and implementation of ST to design a subsequent study. Results Over the course of 6 months, ST’s first prototype was developed during multiple creative sessions. Included was the development of a short 360° VR video, to serve as a base for the mentalization exercises. The final version of ST consisted of 7 individual therapy sessions, incorporating both the VR video and a VR StreetView app. On the basis of the qualitative data collected during the pilot phase, we found preliminary signs of ST’s potential to support adolescents’ perspective-taking abilities specifically. Additionally, using VR to focus on real-life situations that adolescents encounter in their daily lives possibly helps to facilitate communication. However, several challenges and requests concerning the VR hardware and software and the implementation of ST emerged, pointing toward further development of ST as an add-on intervention. These challenges currently limit large-scale implementation, resulting in specific requirements regarding a subsequent study. Conclusions In order to gather more extensive information to shape further development and study treatment effects, a small-scale and individually oriented research design seems currently more suitable than a more standard between-subjects design. Using the reflection on the lessons learned described in this report, a research protocol for a forthcoming study on ST has been developed. By presenting our co-creation journey thus far, we hope to be of inspiration for a more co-creative mindset and in that way contribute to the mutual reinforcement of science and clinical practice.
Low‐intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high‐intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 ± 0.3 Pa, 5 Hz) or high intensity (2.9 ± 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa‐Β ligand‐induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000× g ) obtained after low‐intensity loading and induced by exosomes (100 000× g ) obtained after high‐intensity loading. These osteoclast‐modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT‐independent exosome biogenesis (high intensity), as well as by inhibition of dynamin‐dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast‐modulating effect.
When selling a home, through the choice of the list price, sellers make a trade‐off between achieving a quick sale at a low price or waiting for higher bids. This list‐price setting decision is governed by a discount rate. Using data on housing sales in the Netherlands, we derive gross discount rates under bilateral bargaining and bidding wars. The estimated discount rates are 25‐35 percent, which is considerably higher than long‐run housing market discount rates and may result from the seller's unfamiliarity with the selling process. The rates are higher for sellers that already moved and have a low education. This article is protected by copyright. All rights reserved
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