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Does the structure of dynamic symptom networks depend on baseline psychopathology in students?
No full textNetwork theory conceptualizes mental disorders as systems of dynamic interactions among symptoms and other variables, and proposes that people with psychopathology have distinct networks as compared to healthy people. However, this idea is rarely investigated, and networks are mostly estimated on cross-sectional data. Importantly, as network theory is specified on the within-person level, it is necessary to estimate networks based on intensive time-series data. This study estimated contemporaneous and temporal transdiagnostic networks on time-series data of participants with different levels of psychopathology. 192 university students completed an Ecological Momentary Assessment (EMA) protocol. A newly developed bootstrap method was used to compare the multilevel Vector Autoregressive (mlVAR) effects between groups. Network connectivity did not differ between groups. Only a few edges differed significantly between groups, with small effect sizes. These results suggest that networks of groups of people with different levels of psychopathology might not differ. Explanations and implications for these results, such as the impact of focusing on heterogeneous groups instead of homogeneous groups or individuals, the relevance of node levels, and methodological and analytical decisions, are discussed
Neural evidence for the effects of behavioral memory updating following fear conditioning
No full textExposure therapy for the treatment of pain-related disability relies on extinction learning, forming new safety memories inhibiting fear expression. However, fear often returns. The behavioral memory updating hypothesis posits that a fear memory can be 'updated' to a safe memory while in a malleable state, preventing return-of-fear. To test this hypothesis, 78 adolescents with and without chronic pain (age: Mean=15 y, range=10-24 y) were recruited for a two-day neuroimaging study. Due to incomplete data/excess motion, 55 participants (pain=38; pain-free=17) were included in MRI data analysis. Participants underwent a fear conditioning protocol with a within-subjects 'updating' manipulation: one CS+ (CS+Reminded [CS+R]) was reactivated to achieve a malleable state before extinction, while a second (CS+Not Reminded [CS+NR]) was not. We observed significantly less functional connectivity between the ventromedial prefrontal cortex and the amygdala for the CS+R and CS- compared to the CS+NR, consistent with the purported change in neural circuitry underlying the 'updating' effect, however observed no credible difference in fear ratings between the CS+R and CS+NR. This discrepancy may be crucial to understanding the mixed findings in the field and indicates that while some form of 'updating' may occur, it may be insufficient to reduce reported fear
Genital Modifications in Prepubescent Minors:When May Clinicians Ethically Proceed?
No full textWhen is it ethically permissible for clinicians to surgically intervene into the genitals of a legal minor? We distinguish between voluntary and nonvoluntary procedures and focus on nonvoluntary procedures, specifically in prepubescent minors ("children"). We do not address procedures in adolescence or adulthood. With respect to children categorized as female at birth who have no apparent differences of sex development (i.e., non-intersex or "endosex" females) there is a near-universal ethical consensus in the Global North. This consensus holds that clinicians may not perform any nonvoluntary genital cutting or surgery, from "cosmetic" labiaplasty to medicalized ritual "pricking" of the vulva, insofar as the procedure is not strictly necessary to protect the child's physical health. All other motivations, including possible psychosocial, cultural, subjective-aesthetic, or prophylactic benefits as judged by doctors or parents, are seen as categorically inappropriate grounds for a clinician to proceed with a nonvoluntary genital procedure in this population. We argue that the main ethical reasons capable of supporting this consensus turn not on empirically contestable benefit-risk calculations, but on a fundamental concern to respect the child's privacy, bodily integrity, developing sexual boundaries, and (future) genital autonomy. We show that these ethical reasons are sound. However, as we argue, they do not only apply to endosex female children, but rather to all children regardless of sex characteristics, including those with intersex traits and endosex males. We conclude, therefore, that as a matter of justice, inclusivity, and gender equality in medical-ethical policy (we do not take a position as to criminal law), clinicians should not be permitted to perform any nonvoluntary genital cutting or surgery in prepubescent minors, irrespective of the latter's sex traits or gender assignment, unless urgently necessary to protect their physical health. By contrast, we suggest that voluntary surgeries in older individuals might, under certain conditions, permissibly be performed for a wider range of reasons, including reasons of self-identity or psychosocial well-being, in keeping with the circumstances, values, and explicit needs and preferences of the persons so concerned. Note: Because our position is tied to clinicians' widely accepted role-specific duties as medical practitioners within regulated healthcare systems, we do not consider genital procedures performed outside of a healthcare context (e.g., for religious reasons) or by persons other than licensed healthcare providers working in their professional capacity
Temporal Changes in Fetal and Maternal Parameters in Early-Onset Fetal Growth Restriction:A Multicenter, Retrospective Cohort Study
No full textObjective(s): Timing of birth is complex in early-onset fetal growth restriction (FGR) and the literature is limited regarding the exact sequence of changes in antenatal parameters. This study aimed to examine this sequence in a large early-onset FGR cohort. Design: Multicenter, retrospective cohort study. Setting: Six tertiary care hospitals in the Netherlands. Population: A post hoc analysis of the OPtimal TIming of antenatal COrticosteroids in early-onset fetal growth REstriction (OPTICORE) study was performed. Methods: Repeated measures of antenatal parameters were assessed routinely from diagnosis to birth. Mixed-effects models were used to determine the probability of abnormality (binary) and the trend (Z-score, continuous) over time for each parameter (< 32 and >= 32 weeks). Main outcome measures: The time sequence of changes in fetal and maternal health parameters from diagnosis to birth in early-onset FGR pregnancies. Results: A total of 1453 patients were included, of whom 1025 patients gave birth < 32 weeks and 428 >= 32 weeks, with median gestational ages of 29 + 3 weeks (IQR 27 + 6, 30 + 5) and 34 + 4 weeks (IQR 33 + 0, 37 + 0), respectively. The most apparent changes in fetal parameters in the last days preceding birth comprised: absent/reversed end-diastolic velocity of the umbilical artery and cardiotocography abnormalities. Regarding maternal parameters, an increased probability of antihypertensive agent(s) use was seen shortly preceding birth < 32 weeks. Conclusion(s): This large cohort of early-onset FGR pregnancies provides a time sequence of fetal and maternal health parameters from diagnosis to birth, which could inform clinical management
Prophylactic PDE4 and PDE4B inhibition reduce lesion size and neutrophil infiltration following ischemic stroke in male mice
No full textStroke remains the second leading cause of death worldwide, highlighting the urgent need for novel treatment options. Phosphodiesterase 4 (PDE4) inhibition has been shown to reduce neuroinflammation and improve neurological outcomes in several neurodegenerative diseases, such as multiple sclerosis. Especially the PDE4B gene is known to contribute to the inflammatory reaction. Therefore, we investigated the effects of PDE4 and PDE4B inhibition in ischemic stroke. We used the distal middle cerebral artery occlusion (dMCAO) mouse model to assess inflammatory cell infiltration and lesion size, and complemented the data with in vitro studies on neutrophils. Our results show that prophylactic PDE4 and PDE4B inhibition reduced the lesion size and neutrophil infiltration in vivo, whereas post-stroke administration of these inhibitors did not show an effect. In vitro, neutrophil activation was decreased following PDE4 and PDE4B inhibition. Furthermore, spatial proteomics analysis of the ischemic brain identified C1QBP as a potential contributing factor to the beneficial effects of prophylactic PDE4B inhibition. Taken together, our research provides evidence for a potential role of prophylactic, but not acute PDE4 and PDE4B inhibition in ischemic stroke treatment, especially for patients at risk of recurrent stroke
A method for accurate replication of complex and cell-instructive surface microtopographies
No full textBiomaterial surface topography can modulate cellular behavior and has become a powerful tool for developing highly functional biomaterials for tissue regeneration applications. For example, grained topographies in the microstructure of calcium phosphate ceramics, such as ß-tricalcium phosphates (TCPs), were shown to impact their osteoinductive properties; yet the mechanisms of action underlying interactions of these surface topographies with cells are not fully understood. Probing these types of biological mechanisms is especially challenging because of the combined effects of biomaterial surface chemistry and topography, which are difficult to deconvolute. Previously, hot embossing with an inversely replicated polydimethylsiloxane (PDMS) mold was employed to transfer the topographies of TCPs onto polymer films and investigate their cell-instructive effects independent of the substrate chemistry. This method proved successful for copying the surficial topographies of the ceramics to the polymer substrates. Here, we describe an improved replication method using nickel mold galvanoforming and nanoimprinting to create high-fidelity replicas of micro- and sub-micro-sized topographies of TCPs in thermoplastic polyurethane (TPU). Our findings indicate that using the proposed method, the topography replication depth was greatly improved in both the intermediate molds and the TPU imprints of the TCPs compared to hot embossing method with PDMS mold. This method is particularly suitable for replicating complex, naturally occurring surface topographies onto different polymer films and allows for the reliable investigation of the role of micro- and sub-micro-sized topographies on cell behavior, as well as for developing highly functional biomaterials
A 10-year interval of cardiovascular effects of albuterol in asthma management:Graphical review
No full textAsthma is a widespread chronic respiratory disease that requires effective management to reduce exacerbations and improve patient outcomes. Albuterol (salbutamol), a short-acting beta-2-agonist (SABA), remains a mainstay treatment for acute symptom relief due to its rapid bronchodilatory effect. However, accumulating evidence over the past decade has raised concerns about its cardiovascular safety, particularly in vulnerable populations such as children, elderly individuals, and those with underlying cardiac conditions. This review synthesizes clinical findings from the last ten years (2015–2025) evaluating the cardiovascular effects of albuterol, including tachycardia, arrhythmias, QTc prolongation, and hypotension. Literature across PubMed, Cochrane, and Google Scholar was analyzed to assess frequency, severity, and risk factors associated with these events. Notably, intravenous administration was associated with markedly higher rates of adverse effects, while inhaled formulations remained safer with moderate risk. Pediatric patients on continuous therapy showed increased susceptibility to electrolyte imbalances and hypotension. Although alternatives like levalbuterol demonstrated a reduced cardiovascular risk profile, they were linked with increased healthcare costs and longer hospital stays. The review highlights the importance of risk stratification, personalized dosing, and enhanced monitoring, particularly in high-risk groups, to maximize the therapeutic benefits of SABAs while minimizing cardiovascular harm. Overall, the findings underscore the need for ongoing pharmacovigilance and tailored clinical decision-making when prescribing albuterol in asthma care
TrackHHL:A Quantum Computing Algorithm for Track Reconstruction at the LHCb
No full textIn the future high-luminosity LHC era, high-energy physics experiments face unprecedented computational challenges for event reconstruction. Employing the LHCb vertex locator as a case study we investigate a novel approach for charged particle track reconstruction. The algorithm hinges on minimizing an Ising-like Hamiltonian using matrix inversion. Solving this matrix inversion classically achieves reconstruction efficiencies akin to current state-of-the-art algorithms. Exploiting the Harrow-Hassidim-Lloyd (HHL) quantum algorithm for linear systems holds the promise of an exponential speedup in the number of input hits over its classical counterpart, contingent on the conditions of efficient quantum phase estimation (QPE) and effectively reading out the algorithm’s output. This contribution builds on previous work by Nicotra et al. [1] and strives to fulfill these conditions and further streamlines the algorithm’s circuit depth by a factor up to 104. Our version of the HHL algorithm restricts the QPE precision to one bit, largely reducing circuit depth and addressing HHL’s readout issue. Furthermore, this allows for the implementation of a post-processing algorithm that reconstructs event Primary Vertices (PVs). The findings presented here aim to further illuminate the potential of harnessing quantum computing for the future of particle track reconstruction in high-energy physics
A state of denial: comparing the Netherlands' approach to the fundamental right of social security and social assistance with the current international and European social rights doctrine
No full textHuman rights are indivisible. This means that all human rights are considered to be universal, interdependent and interrelated. Even after the separation of economic, social and cultural rights from civil and political rights, the United Nations consistently upheld the principle that all human rights should be treated equally. Denying the equal status of socio-economic rights in relation to civil rights can have adverse consequences for individuals. This is illustrated by the Netherlands, which focuses primarily on civil rights and relegates socioeconomic rights to a secondary position, resulting in an asymmetrical protection of human rights and depriving socio-economic rights of their potential to protect individuals against repressive state policies. This article explores the different approaches to socio-economic human rights, focusing in particular on the right to social security. It argues that the Netherlands’ approach to this right has deviated from the international and European human rights doctrine. This is because international and European human rights authorities have developed an approach to the human right to social security that is consistent with the concept of indivisibility, while the Netherlands has remained in a state of denial