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Return of fear after successful exposure therapy for a phobia is a common clinical challenge. A previous study on mice demonstrated that the persistent attenuation of remote fear memories can be achieved by combining histone deacetylase inhibitors (HDACis) with fear-memory retrieval prior to extinction training.
Methods
To evaluate the translational potential of this approach, we conducted a randomized, double-blind, placebo-controlled trial. Forty-eight individuals with DSM-IV spider phobia received either HDACi valproic acid (VPA, 500 mg) or a placebo prior to the retrieval of fear memory, followed by exposure therapy in virtual reality.
Results
No significant group difference was found in terms of behavioral change on the behavioral approach test at 3 months follow-up and baseline (primary outcome). However, the VPA group displayed significantly reduced fear in two self-report questionnaires related to spider phobia (Fear of Spiders Questionnaire; Spider Phobia Beliefs Questionnaire) as compared to the placebo group. No group differences were observed for psychophysiological indicators of fear.
Conclusions
The favorable impact of a single administration of VPA in combination with fear-memory retrieval prior to exposure therapy suggests that it might be an effective way to enhance symptom improvement at the subjective level in the treatment of phobias. Further studies need to investigate the conditions under which an improvement on the psychophysiological and behavioral levels can be achieved as well.
Cyber breaches pose a significant threat to both enterprises and society. Analyzing cyber breach data is essential for improving cyber risk management and developing effective cyber insurance policies. However, modeling cyber risk is challenging due to its inherent characteristics, including sparsity, heterogeneity, heavy tails, and dependence. This work introduces a cluster-based dependence model that captures both temporal and cross-group dependencies, providing a more accurate representation of multivariate cyber breach risks. The proposed framework employs a cluster-based kernel approach to model breach severity, effectively handling heterogeneity and extreme values, while a copula-based method is used to capture multivariate dependence. Our findings, validated through both empirical and synthetic studies, demonstrate that the proposed model effectively captures the statistical characteristics of multivariate cyber breach risks and outperforms commonly used models in predictive accuracy. Furthermore, we show that our approach can enhance cyber insurance pricing by generating more profitable insurance contracts.
This paper examines the likely economic consequences of a unilateral US trade policy, particularly those involving across-the-board tariffs and retreat from multilateral commitments. Drawing on computable general equilibrium (CGE) models, dynamic macroeconomic frameworks, and a rich body of empirical literature, the paper demonstrates that the static efficiency losses, estimated by standard trade models, understate the true costs of protectionism. It identifies five key amplification channels – loss of economies of scale, supply chain fragility, diminished technological spillovers, investment hold-up under policy uncertainty, and financial market reactions – that interact to depress both short-run output and long-run growth potential. The analysis estimates that comprehensive unilateral trade measures could reduce US GDP by 2–3% in the short term and lower the long-term growth trajectory by 0.4–0.7 percentage points annually. While some strategic interventions may yield resilience or national security benefits, the paper concludes that unilateralism generates systemic economic risks and should be approached with caution. The findings underscore the need for integrated policy frameworks that combine targeted trade tools with domestic support and international cooperation.
Inequality has increased over recent decades in many advanced industrial democracies, but taxes have rarely become more progressive. One possible explanation for the lack of a policy response is that, despite rising inequality, voters support higher taxes on incomes weakly, if at all. Using original representative surveys in Austria and Germany, we elicit voters’ preferences over the progressivity of income tax policy and examine whether exposing them to accurate information about inequality affects those preferences. Voters, we find first, express an abstract preference for progressivity but concretely support tax plans that are only somewhat more progressive than the status quo in Austria and less progressive than the status quo in Germany. Second, we find evidence that certain kinds of information about inequality moderately increase progressive tax preferences in Germany; however, we find no equivalent effects in Austria. While information on inequality does seem able to affect tax policy views in certain contexts, it seems unlikely that lack of this information can fully account for the lack of rising redistribution through the income tax system in the face of increasing inequality.
The purpose of this study is to examine the existing literature on end-of-life dream experiences and bucket list fulfillments among terminally ill individuals receiving hospice and/or palliative care.
Methods
A scoping review registered on Open Science Framework was conducted in accordance with the guidelines for Scoping reviews (PRISMA-ScR). An electronic search of literature was generated from EBSCO databases published until June 2024. Studies were included if they described and evaluated the effects of bucket lists and/or end-of-life wish fulfillment.
Results
This review identified 2,234 studies, and 11 of these were included in the review. Four major themes were established using thematic content analysis: (1) impact on holistic well-being, (2) role of family in wish fulfillment, (3) cultivation of gratitude, and (4) collaborative leadership in wish fulfillment. In wish fulfillment, the results significantly pointed to the need for more intricate evaluation among patients and interventions that cover beyond the physical aspect.
Significance of results
Palliative and hospice care settings should work toward securing sustainable funding for structured wish-fulfillment programs to address existing accessibility gaps and further enhance the holistic nature of care in these settings. Wish-fulfillment interventions represent a powerful tool in enhancing dignity and holistic experiences for terminally ill patients. Future research efforts could strengthen programs ensuring every individual is able to achieve a sense of peace, fulfillment, and closure during their care trajectory.
This paper presents a detailed robustness analysis of three nonlinear filtering algorithms: the unscented Kalman filter, the cubature Kalman filter, and the ensemble Kalman filter, applied to aircraft state estimation for fixed-wing flight dynamics. The study focuses on estimating critical longitudinal flight parameters such as true airspeed, angle-of-attack, pitch angle and pitch rate using pitch angle measurements. A nonlinear aircraft model is formulated, and each filtering technique is implemented and evaluated under multiple scenarios, including sensor noise, initial state mismatches and plant-model uncertainties. Simulation results across four cases, ranging from ideal conditions to $95{\mathrm{\% }}$ mismatch, demonstrate that the unscented Kalman filter consistently delivers the most accurate and robust estimates, especially for velocity and pitch rate. The cubature Kalman filter offers a trade-off between estimation accuracy and computational efficiency, while the ensemble Kalman filter shows significant sensitivity to uncertainties but performs relatively better in estimating the angle-of-attack under severe mismatch conditions. This comparative study provides valuable insights for selecting appropriate filtering strategies in aerospace applications, particularly where robustness and reliability under uncertainty are crucial.
Given a family of pairs over a smooth curve whose general fiber is a log Calabi–Yau pair in a fixed bounded family, suppose there exists a divisor on the family whose restriction on a general fiber is ample with bounded volume. We show that if the total space of the family has relatively trivial log canonical divisor and the special fiber has slc singularities, then every irreducible component of the special fiber is birationally bounded.
Negami found an elegant splitting formula for the Tutte polynomial. We present an analogue of this for Bollobás and Riordan’s ribbon graph polynomial, and for the transition polynomial. From this we deduce a splitting formula for the Jones polynomial.
Dissociative experiences are common transdiagnostically, and particularly prevalent in psychosis. Such experiences have long been under-recognised in routine clinical practice, despite evidence that dissociation is related to clinical complexity and increased risk of self-harm and suicidality. Adopting a symptom-specific, targeted approach to conceptualisation and intervention for dissociation may help improve outcomes.
Aims:
The evidence base for psychological treatments targeting dissociation is building, but training and guidance for clinicians remains sparse. This review outlines a preliminary approach to the treatment of a subtype of dissociative experience (felt sense of anomaly dissociation), based on emerging research evidence and clinical practice. The guidance is tailored to the context of psychosis, and may also have broader clinical relevance.
Method:
We present symptom-specific guidance for clinicians, including factors to consider in the assessment, formulation, and intervention for felt sense of anomaly dissociation in the context of psychosis, and reflections on process issues. We present a cognitive behavioural model, where affect-related changes are interpreted as an internal threat, driving a maintenance cycle of catastrophic appraisals and safety behaviours. Using this formulation, evidence-based therapy techniques familiar to most readers can then be applied.
Conclusions:
It is important for clinicians to consider dissociation. As well as generating new avenues for translational intervention research, we anticipate that the novel insights and specific advice outlined here will be of use to professionals working with dissociation in psychosis (and beyond). Encouragingly, we demonstrate that widely used, evidence-based skills and techniques can be employed to address distress arising from dissociation.
Although life stressors are known risk factors for suicide, the specific stressor types that most strongly precipitate suicidal outcomes, and on what timescale, remain poorly understood. Based on existing theory, we investigated whether objectively rated interpersonal stressors, especially social and targeted rejection stressors, are proximally associated with increased likelihood of suicidal ideation and behavior.
Method
Using an objectively rated contextual threat interview to assess stressful life events, and a timeline followback procedure for assessing suicide-related outcomes, we examined how the severity of four types of acute life events (i.e. non-interpersonal, interpersonal without social rejection, social rejection without targeted rejection, and targeted rejection) were temporally associated with the likelihood of same-day and next-day suicidal ideation and behavior over 16 months in 143 young adults (Mage = 25.27, SD = 4.65) with recent suicidal ideation or behavior.
Results
After controlling for prior-day suicidal ideation and non-interpersonal stressors, daily within-person increases in interpersonal stressor severity were related to higher odds of same-day (but not next-day) suicidal ideation. Additionally, greater increases in targeted rejection severity were uniquely related to increased likelihood of both same-day and next-day suicidal behavior after controlling for prior-day suicidal behavior and other types of stressors.
Conclusions
Interpersonal stressors are strong, proximal risk factors for suicidal ideation and behavior, and these effects are particularly strong for targeted rejection life events. Clinicians should thus assess recent interpersonal and, especially, targeted rejection stressors when evaluating acute suicide risk, and may reduce such risk by helping patients stabilize and strengthen their social relationships.
This article provides new exploratory information on child support amounts expected for non-resident fathers of children living with low-income, unemployed mothers in Colombia, Finland, Peru, the United States, and Uruguay. Using vignette data obtained through extensive interviews with judicial and social service personnel and child support experts, we investigated whether child support is expected and its amount when single mothers are unemployed, considering four different levels of earnings for fathers. In all countries but Finland, child support is expected when the father has only temporary employment. For the lowest income fathers, child support expectations in Colombia, Peru, and Uruguay are similar or higher than the United States and higher in Finland. In all countries except Colombia, child support expectations are higher when father’s income is higher. We discuss implications for policy and future research.
Real-world evidence (RWE) is increasingly used to assess and make regulatory decisions on health technologies. However, its application in healthcare payer decision-making is less well-known.
Objectives
The objectives of this study were to (i) review the recent literature on how RWE has been used by healthcare payers, (ii) highlight barriers that limit the use of RWE in payer decision making, and (iii) explore how RWE has been used in various funding arrangements between payers and manufacturers. The benefits of utilizing RWE are also discussed.
Methods
A scoping review was conducted on articles published between 2014 and 2025 in PubMed (Medline), OVID EMBASE, Cochrane Library, and ProQuest Dissertations and Theses Global. Eligible articles were those written in English that discussed the use of real-world evidence among healthcare payers/decision-makers for health technology reimbursement decisions.
Results
Nineteen articles were selected for full-text review based on the inclusion criteria. The review highlighted payers’ interest in incorporating RWE into funding and reimbursement decisions to address uncertainty in the performance of new health technologies. However, a lack of standards for collecting, analyzing, and reporting RWE limits its use. Little is known about how RWE is used in reimbursement decisions since contractual arrangements between payers and manufacturers are confidential.
Conclusions
Although payers are interested in using RWE to inform funding and reimbursement decisions, there are concerns regarding the scientific rigor used to generate such evidence. Having more insight into the contractual arrangements between payers and manufacturers would help to better understand how RWE informs these agreements.
This article traces the visual culture of human genetic engineering over the past decade, focusing on the CRISPR genome editing technology. We argue that the representations surrounding CRISPR exemplify, and to an extent define, this visual culture. We examine the history of CRISPR, particularly its human applications from 2012 to 2022, through a periodization that includes the CRISPR craze, gene therapy initiatives, the He Jiankui controversy and clinical trials. Employing an expanded interpretation of intermediality within science communication, this work addresses the role of figuration across the relationships between specialist science reporting and the mainstream press and between traditional and social media. Using a mixed-methods approach combining visual and social-media analysis, the article presents an empirical analysis of three key figures – the double helix, the scientist and the human subject – and their roles across the discussed phases. The study concludes by articulating the stabilizing, amplifying and affective functions of intermedial figuration within science communication.