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The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.
Methods
Our approach involved a two-step procedure. First, we conducted a review of prior studies utilizing the PAI, evaluating each study using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). We specifically assessed whether the studies adhered to two standards of predictive modeling: refraining from using leave-one-out cross-validation (LOO CV) and preventing data leakage. Second, we examined the impact of deviating from these methodological standards in real data. We employed both a traditional approach violating these standards and an advanced approach implementing them in two large-scale datasets, PANIC-net (n = 261) and Protect-AD (n = 614).
Results
The PROBAST-rating revealed a substantial risk of bias across studies, primarily due to inappropriate methodological choices. Most studies did not adhere to the examined prediction modeling standards, employing LOO CV and allowing data leakage. The comparison between the traditional and advanced approach revealed that ignoring these standards could systematically overestimate the utility of the PAI.
Conclusion
Our study cautions that violating standards in predictive modeling may strongly influence the evaluation of the PAI's utility, possibly leading to false positive results. To support an unbiased evaluation, crucial for potential clinical application, we provide a low-bias, openly accessible, and meticulously annotated script implementing the PAI.
As readers of this journal can attest to, although philosophers and economists are somewhat used to talking to and learning from each other, it tends to be the subset of philosophers working in decision theory, philosophy of science, and particular areas of ethics and political philosophy that contribute to our interdisciplinary field of research. The book that is the subject of this review symposium, Anna Mahtani’s The Objects of Credence (Oxford University Press, 2024), is a wonderful exemplar of what can be learned when a different branch of philosophy is brought to bear on central questions in this field. Both philosophers and economists talk about and work with credences, or degrees of belief, all the time. These are usually modelled as probabilities, which are in turn usually thought of as attaching to propositions. But it has long been argued by philosophers of language that propositions cannot be the objects of credence. Mahtani’s book is an investigation into all that begins to unravel once we accept this insight. The results have profound implications both for rational choice modelling and for welfare economics.
The effective reproduction number $ R $ was widely accepted as a key indicator during the early stages of the COVID-19 pandemic. In the UK, the $ R $ value published on the UK Government Dashboard has been generated as a combined value from an ensemble of epidemiological models via a collaborative initiative between academia and government. In this paper, we outline this collaborative modelling approach and illustrate how, by using an established combination method, a combined $ R $ estimate can be generated from an ensemble of epidemiological models. We analyse the $ R $ values calculated for the period between April 2021 and December 2021, to show that this $ R $ is robust to different model weighting methods and ensemble sizes and that using heterogeneous data sources for validation increases its robustness and reduces the biases and limitations associated with a single source of data. We discuss how $ R $ can be generated from different data sources and show that it is a good summary indicator of the current dynamics in an epidemic.
Behavioral welfare economics usually aims at mere means paternalism, helping agents better pursue their own goals. This paper discusses one initially promising way to inform policies addressed at agents who violate expected utility theory (EUT), namely what I call “CPT debiasing.” I argue that this approach is problematic even if we grant the normative authority of EUT, the descriptive adequacy of CPT (cumulative prospect theory), and the general acceptability of means paternalism. First, it is doubtful whether the CPT utility function measures what its proponents intend. Second, by imposing risk neutrality on agents, the approach involves a more problematic paternalism.
Chater & Loewenstein argue that i-frame research has been coopted by private interests opposed to system-level reform, leading to ineffective interventions. They recommend that behavioural scientists refocus on system-level interventions. We suggest that the influence of private interests on research is problematic for wider normative and epistemic reasons. A system-level intervention to shield research from private influence is needed.
The Big Exchange project investigates large-scale exchange systems in Eurasia and Africa (8000–1 BC). We concentrate on raw materials of known origin (‘sourced finds’). Network analysis of tools and artificial intelligence methods are used to analyse the combined data sets. We invite broad collaboration on bimodal exchange networks.
This chapter by the philosopher Johanna Thoma focuses on the ‘moral proxy problem’, which arises when an autonomous artificial agent makes a decision as a proxy for a human agent, without it being clear for whom specifically it does so. Thoma recognises that, in general, there are broadly two categories of agents an artificial agent can be a proxy for: low-level agents (individual users or the kinds of human agents artificial agents are usually replacing) and high-level agents (designers, distributors, or regulators). She argues that we do not get the same recommendations under different agential frames: whilst the former suggests the agents be programmed without risk neutrality, which is common in choices made by humans, the latter suggests the contrary, since the choices are considered part of an aggregate of many similar choices. The author argues that the largely unquestioned implementation of risk neutrality in the design of artificial agents deserves critical scrutiny. Such scrutiny should reveal that the treatment of risk is intimately connected with our answer to the questions about agential perspective and responsibility.
Cumulative oxidative damage from the unavoidable formation of reactive oxygen species (ROS) contributes to seed ageing. Low-molecular-weight (LMW) antioxidants, such as water-soluble glutathione (GSH) and lipid-soluble tocochromanols, can prevent ROS from causing damage, especially when antioxidant enzymes are inactive due to desiccation. However, loss of tocochromanols does not always accompany seed ageing, such as during accelerated ageing or controlled deterioration, despite the presence of oxygen and prevalent loss of GSH. To assess relationships between total germination (TG) and antioxidant changes under storage conditions with practical relevance, commercial seeds of Cucumis sativus, Daucus carota, Helianthus cucumerifolius, Latuca sativa, Lepidium sativum, Phaseolus vulgaris and Raphinus sativus of the same cultivar were obtained over multiple years and stored under ambient conditions (21.9 ± 2.1°C; 36.8 ± 6.6% relative humidity). Sigmoidal fitting of TG revealed time to when 50% of seeds had lost viability, which ranged from <5 years (D. carota) to >15 years (C. sativus). Cellular redox states were quantified via the half-cell reduction potential of LMW thiol/disulphide couples. These negatively correlated with TG (i.e. cell redox states were more oxidized in lots with lower TG), with an average R2 value of 0.62 for the most abundant thiol (GSH, or γ-glutamyl-cysteine in P. vulgaris). Concentrations of tocochromanols positively correlated with TG, with an average R2 value of 0.50 for the most abundant tocochromanol (γ or α in L. sativa and H. cucumerifolius). Therefore, during viability loss under ambient ageing conditions leading to the cytoplasm having a glassy state, the lipid domain in all species experienced oxidative damage.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
Design:
Longitudinal study
Participants:
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
Measurements:
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
Results:
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
Conclusions:
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
The present study aimed to assess the current state of breast-feeding promotion in hospitals and the prevalence of breast-feeding during the first year of life in Germany and to compare the results with a study 20 years earlier.
Design:
In the studies on ‘breast-feeding and infant nutrition in Germany’ named ‘SuSe’, a cross-sectional survey in hospitals was combined with a subsequent prospective survey of breast-feeding and infant nutrition during the first year of life (0·5, 2, 4, 6 and 12 months after birth) in mother–infant pairs who were recruited in the hospitals. Written questionnaires and phone calls were used in SuSe I and web-based questionnaires in SuSe II. Breast-feeding promotion and prevalence were evaluated using recommendations from the WHO and the UNICEF.
Setting:
Two nationwide surveys SuSe I (1997–1998) and SuSe II (2017–2019).
Participants:
In SuSe I, 177 hospitals and 1717 mother–infant pairs and in SuSe II 109 hospitals and 962 mother–infant pairs were included.
Results:
In SuSe II, hospitals implemented seven of the WHO ‘Ten Steps to Successful Breastfeeding’ to a greater extent than the hospitals in SuSe I. More mothers exclusively breastfed for 4 months (57 % v. 33 %) and continued breast-feeding until 6 (78 % v. 48 %) and 12 months (41 % v. 13 %). In both studies, exclusive breast-feeding decreased between 4 and 6 months of age due to the introduction of complementary feeding.
Conclusions:
In Germany, breast-feeding habits have come closer to the recommendations over the last 20 years.
The three-dimensional characterization of distributed particle properties in the micro- and nanometer range is essential to describe and understand highly specific separation processes in terms of selectivity and yield. Both performance measures play a decisive role in the development and improvement of modern functional materials. In this study, we mixed spherical glass particles (0.4–5.8 μm diameter) with glass fibers (diameter 10 μm, length 18–660 μm) to investigate a borderline case of maximum difference in the aspect ratio and a significant difference in the characteristic length to characterize the system over several size scales. We immobilized the particles within a wax matrix and created sample volumes suitable for computed tomographic (CT) measurements at two different magnification scales (X-ray micro- and nano-CT). Fiber diameter and length could be described well on the basis of the low-resolution micro-CT measurements on the entire sample volume. In contrast, the spherical particle system could only be described with sufficient accuracy by combining micro-CT with high-resolution nano-CT measurements on subvolumes of reduced sample size. We modeled the joint (bivariate) distribution of fiber length and diameter with a parametric copula as a basic example, which is equally suitable for more complex distributions of irregularly shaped particles. This enables us to capture the multidimensional correlation structure of particle systems with statistically representative quantities.
This paper defends revealed preference theory against a pervasive line of criticism, according to which revealed preference methodology relies on appealing to some mental states, in particular an agent’s beliefs, rendering the project incoherent or unmotivated. I argue that all that is established by these arguments is that revealed preference theorists must accept a limited mentalism in their account of the options an agent should be modelled as choosing between. This is consistent both with an essentially behavioural interpretation of preference and with standard revealed preference methodology. And it does not undermine the core motivations of revealed preference theory.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Methods
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
Results
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Conclusions
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration.
Methods
Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates.
Results
Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates.
Conclusions
Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.
As evidence for the second process of the Embracing factor, the target article characterizes being moved as a mixed emotion linked to sadness through metonymy. We question these characterizations and argue that emotions should not be equated with their vernacular labels.