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To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.
Aim
To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.
Methods
A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.
Results
Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).
Conclusions
Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.
Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.
Aims
To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.
Method
We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.
Results
Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.
Conclusions
We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.
Biomedical research on advanced cryopreservation has spillover effects on innovation in the food and agricultural sector. Advanced biopreservation technology has three key domains of impact in the food system: (1) improving efficiencies in storage and utilization of gametes and organoids for plant and animal breeding; (2) isochoric methods for preservation of fresh food products; and (3) in biorepositories for storage of genetic resources for agriculturally significant plants and livestock species.
This article presents a framework of ethical analysis for anticipatory evaluation of advanced biopreservation technologies and employs the framework illustratively in three domains. The framework features four clusters of general ethical considerations: (1) Producing Benefits, Minimizing Harms, Balancing Benefits, Risk, and Costs; (2) Justice, Fairness, Equity; (3) Respect for Autonomy; and (4) Transparency, Trustworthiness, and Public Trust.
Advanced biopreservation technologies using subzero approaches such as supercooling, partial freezing, and vitrification with reanimating techniques including nanoparticle infusion and laser rewarming are rapidly emerging as technologies with potential to radically disrupt biomedicine, research, aquaculture, and conservation. These technologies could pause biological time and facilitate large-scale banking of biomedical products including organs, tissues, and cell therapies.
This article explores how time-related metaphors frame advanced cryopreservation technologies in environmental conservation. Cryopreservation “stops” or “freezes” biological time and “buys time” desperately needed to preserve species and ecosystems. We advance a framing of these technologies as logistical, highlighting how they create opportunities to shift materials, knowledge, and decision-making power through space and time. As logistical technologies, advanced cryopreservation techniques require active planning in the present rather than deferring responsibility and accountability to the future.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
The deep regolith of the southeastern United States has undergone rapid erosion in the last two centuries due to intensive agricultural practices, which has altered the landscape and its inherent fertility. Parent material, landscape position, and land use are important factors in controlling the mineral and elemental composition of soil profiles. Independent quantitative X-ray diffraction (QXRD) and whole-rock chemical analysis of eight weathering profiles agreed well and allow mineral reaction pathways to be constrained as particles are conveyed in the subsurface. QXRD analysis of saprolite, argillic, and soil A-horizons in the profiles highlights the imprint of bedrock on the regolith, which includes Neoproterozoic meta-tonalitic to meta-granodioritic and Paleozoic meta-granitic to biotite- and amphibolite-gneissic lithologies. Also, aeolian input slightly influenced A-horizon composition. The clay mineral assemblage is dominated by kaolinite, but profiles differ in the amount of interstratified clay minerals, halloysite, hematite, goethite, and gibbsite. Rare-earth element totals vary between 30 and 1048 ppm and are generally correlated positively with clay and clay mineral content. Eu and Ce anomalies reflect parent rocks and subsequent hydrolysis and redox history, with trends depending upon landscape position and clay content in the weathering profile. Weathering profiles on a high-order interfluve and those that were actively cultivated have thick argillic horizons (as defined by clay mineral abundance) and are depleted in alkali and alkaline-earth elements. Profiles proximally developed on old-field pine and never-cultivated hardwood forest land do not show large differences in mineral composition trends, whereas profiles on old-field sites with ongoing cultivation exhibit assemblages enriched in clay minerals and (oxyhydr)oxides. Old-field pine sites that were historically eroded by previous cultivation tend to have shallower and thinner argillic horizons, which may well impact critical-zone processes involving gas and water fluxes. This study highlights that mineral compositions of deep regolith, saprolite, and shallow soil horizons are dependent on local geomorphology (i.e. watershed- and hillshed-orders). Quantifying soil and regolith compositional trends across the landscape is a prerequisite for determining rates of chemical and physical erosion on human and geologic time scales.
COVID-19 misinformation proliferating online has led to adverse health and societal consequences. Older adults are a particularly vulnerable population due to increased risk for both COVID-19 related complications and susceptibility to, as well as sharing of, misinformation on social networking sites. The present study aimed to: 1) investigate differences in COVID-19 headline accuracy discernment and online sharing of COVID-19 misinformation in older and younger adults; and 2) examine individual differences in global cognition, health literacy and verbal IQ in online sharing of COVID-19 misinformation.
Participants and Methods:
Fifty-two younger (age 18 to 35 years) and fifty older adults (age 50 and older) completed a telephone neurocognitive battery, health literacy and numeracy measures and self-report questionnaires. Participants also completed a social media headline-sharing experiment (Pennycook et al.,2020) in which they were presented true and false COVID-19 headlines and asked to indicate: 1) the likelihood that they would share the story on social media; and 2) the factual accuracy of the story.
Results:
A repeated measures multivariate analysis of variance controlling for gender and race/ethnicity showed no effects of age (p=.099), but a significant interaction between actual COVID-19 headline accuracy and likelihood of sharing (p<.001), such that accuracy is more strongly related to sharing false headlines (r=-.64) versus true headlines (r=-.43). Moreover, higher likelihood of sharing false COVID-19 headlines was associated with lower verbal IQ and numeracy skills in older adults (rs=-.51--.40; ps<.01) and with lower verbal IQ, numeracy, and global cognition in younger adults (rs=-.66--.60; ps<.01).
Conclusions:
Findings indicate that headline accuracy judgements are an important predictor of sharing COVID-19 misinformation in both older and younger adults. Further, individual differences in cognition, IQ, and numeracy may predict the likelihood of misinformation sharing in younger adults, while IQ and numeracy skills may act as important antecedents of misinformation sharing in older adults. Future work might leverage modern, neuropsychologically-based psychoeducation approaches to improving health and science literacy related to COVID-19.
The GINI project investigates the dynamics of inequality among populations over the long term by synthesising global archaeological housing data. This project brings archaeologists together from around the world to assess hypotheses concerning the causes and consequences of inequality that are of relevance to contemporary societies globally.
Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.
Methods
We addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined.
Results
A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure.
Conclusions
These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
This essay explores the philosophical texts and ideas that exerted an influence on Sebald. His personal library was highly selective, containing the works of unconventional thinkers such as Elias Canetti, but omitting most of the major figures of German philosophy along with post-structuralist writers. Ludwig Wittgenstein, however, inspired Sebald’s early film scripts and his life provided biographical details in Austerlitz and Die Ausgewanderten. Sebald expressed an affinity for, and his literary style evidenced, the pre-rational assemblage of Claude Lévi-Strauss’s ‘system of bricolage’, in the way that his works can resemble a scrapbook of clippings, personal recollections, visual images, etc. Although he detested Heidegger, phenomenology pervaded Sebald’s work. For example, the Liverpool Street Station episode in Austerlitz evidenced Bachelard’s ‘theatre of the past’, and he made use of Merleau-Ponty’s ‘pre-human gaze’ in his essay on Jan Peter Tripp. Sebald’s liking for the pre-rational extended to an interest in Gnosticism, Zoroastrianism, superstition and other overlooked schools of thought and philosophy. Zoroastrianism, for example, influenced his early poetry. This essay concludes that Sebald’s deep interest in metaphysics is key for a full understanding of his critical and literary writings.
Alopecia areata (AA) is an immunological disorder characterised by hair loss. Individuals with AA report high levels of social anxiety. One intervention that holds potential for reducing social anxiety in individuals with AA is mindfulness-based cognitive therapy (MBCT).
Aims:
Our key aim was to investigate whether MBCT reduces social anxiety in individuals with AA. The study also investigated whether MBCT reduces depression, general anxiety, and increases quality of life and increases trait mindfulness in individuals with AA.
Method:
Five participants with AA took part in an 8-session in-person MBCT intervention. A multiple-baseline single-group case series design was adopted. Idiographic measures of social anxiety were measured each day from baseline, through intervention, to follow-up. Standardised questionnaires of trait mindfulness, social anxiety, depression, anxiety, and quality of life were completed at baseline, post-intervention, and at 4-week follow-up.
Results:
All participants completed the MBCT course, but one participant was excluded from the idiographic analysis due to a high amount of missing data. The remaining four participants demonstrated reductions in idiographic measures of social anxiety from baseline to follow-up. These effects were larger between baseline and follow-up, than between baseline and post-intervention. Two participants demonstrated significant improvement in standardised measures of wellbeing from baseline to follow-up – they also practised mindfulness most regularly at home between sessions.
Conclusion:
MBCT may be effective in reducing social anxiety and improving wellbeing in individuals with AA, although this might be dependent on the extent to which participants regularly practise mindfulness exercises.
One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.
OBJECTIVES/GOALS: To test the effect of a trusted Community Health Worker (CHW) support model to increase accessibility, feasibility and completion of COVID-19 home-testing in Native American and Latino communities. METHODS/STUDY POPULATION: We conducted a multi-site pragmatic randomized controlled trial among adult Native Americans and Latinos from the Flathead reservation in Montana and Yakima Valley in Washington. Participants were block randomized by site location and age to either an active or passive study arm. Participants in the active arm received assistance with online COVID-19 test kit registration and virtual swabbing support from CHWs, while the passive study arm received the standard-of-care support from the COVID-19 home testing kit vendor. Simple and multivariate logistic regression modeled the association between home-testing distribution mechanism and test completion. Multivariate models included community and sex as covariates. Descriptive feedback was collected in a post-test survey. RESULTS/ANTICIPATED RESULTS: Overall, 63% of the 268 enrolled participants completed COVID-19 tests, and 50% completed tests yielding a valid result. Active arm participants had significantly higher odds of test completion (OR 1.66, 95% CI: [1.01, 2.75], p-value=0.04). Differences were most pronounced among adults ≥60 years, with 84% completing testing kits in the active arm, compared to 58% in the passive arm (p=0.07). Ease of use and not having to leave home were top positive aspects of the home-based test while transporting and mailing samples to lab and long/overwhelming instructions were cited as negative aspects. Most test completers (93%) were satisfied with their experience and 95% found CHW assistance useful. Sample expiration and insufficient identifiers were top causes of non-valid test results. DISCUSSION/SIGNIFICANCE: While test completion rates were low in both study arms, the CHW support led to a higher COVID-19 test completion rate, particularly among older adults. Still, CHW support alone does not fully eliminate testing barriers. Socio-economic differences must be accounted for in future product development for home-based testing to improve health equity.
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
For decades, quantitative psychologists have recommended that authors report effect sizes to convey the magnitude and potential clinical relevance of statistical associations. However, fewer than one-third of neuropsychology articles published in the early 2000s reported effect sizes. This study re-examines the frequency and extent of effect size reporting in neuropsychology journal articles by manuscript section and over time.
Methods:
A sample of 326 empirical articles were drawn from 36 randomly selected issues of six neuropsychology journals at 5-year intervals between 1995 and 2020. Four raters used a novel, reliable coding system to quantify the extent to which effect sizes were included in the major sections of all 326 articles.
Results:
Findings showed medium-to-large increases in effect size reporting in the Methods and Results sections of neuropsychology journal articles that plateaued in recent years; however, there were only very small and nonsignificant changes in effect size reporting in the Abstract, Introduction, and Discussion sections.
Conclusions:
Authors in neuropsychology journals have markedly improved their effect size reporting in the core Methods and Results sections, but are still unlikely to consider these valuable metrics when motivating their study hypotheses and interpreting the conceptual and clinical implications of their findings. Recommendations are provided to encourage more widespread integration of effect sizes in neuropsychological research.
Seabirds are highly threatened, including by fisheries bycatch. Accurate understanding of offshore distribution of seabirds is crucial to address this threat. Tracking technologies revolutionised insights into seabird distributions but tracking data may contain a variety of biases. We tracked two threatened seabirds (Salvin’s Albatross Thalassarche salvini n = 60 and Black Petrel Procellaria parkinsoni n = 46) from their breeding colonies in Aotearoa (New Zealand) to their non-breeding grounds in South America, including Peru, while simultaneously completing seven surveys in Peruvian waters. We then used species distribution models to predict occurrence and distribution using either data source alone, and both data sources combined. Results showed seasonal differences between estimates of occurrence and distribution when using data sources independently. Combining data resulted in more balanced insights into occurrence and distributions, and reduced uncertainty. Most notably, both species were predicted to occur in Peruvian waters during all four annual quarters: the northern Humboldt upwelling system for Salvin’s Albatross and northern continental shelf waters for Black Petrels. Our results highlighted that relying on a single data source may introduce biases into distribution estimates. Our tracking data might have contained ontological and/or colony-related biases (e.g. only breeding adults from one colony were tracked), while our survey data might have contained spatiotemporal biases (e.g. surveys were limited to waters <200 nm from the coast). We recommend combining data sources wherever possible to refine predictions of species distributions, which ultimately will improve fisheries bycatch management through better spatiotemporal understanding of risks.