We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Ketamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine–psychotherapy for TRD to our knowledge.
Aims
This secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential mechanisms of the Montreal Model of ketamine–psychotherapy for TRD, with or without music.
Method
A two-centre, single-blinded, RCT conducted in Montreal, Canada, between January 2021 and August 2022 (NCT04701866). Participants received ketamine–psychotherapy for TRD – six subanaesthetic infusions over 4 weeks and psychological support – with either music or matched non-music support during ketamine doses, as per random group assignments. The primary therapeutic outcome was the Montgomery–Åsberg Depression Rating Scale, assessed by blinded raters. Psychedelic-like experiences, evaluated by the Mystical Experience Questionnaire and Emotional Breakthrough Inventory, and their session-by-session relationships with depression were explored with multilevel, time-lagged covariate models with autoregressive residuals.
Results
Thirty-two participants with severe and highly comorbid TRD, including high rates of personality disorder and suicidality, received 181 ketamine infusions. Therapeutic outcomes and psychedelic experiences did not differ between music (n = 15) and non-music (n = 17) interventions. Both groups experienced significant reductions in clinician-rated and self-reported depression (d = 1.2 and d = 0.87, respectively; p < 0.001), anxiety (d = 0.8, p < 0.001) and suicidality (d = 0.4, p < 0.05) at 4 weeks, fully maintained at 8-week follow-up. Ketamine experiences were highly emotional and mystical. Converging analyses supported mystical-like ketamine experiences as mechanisms of its antidepressant effects.
Conclusions
This trial found large and notably sustained benefits of ketamine–psychotherapy for severe TRD, with or without music, and psychedelic experiences of comparable intensity to those observed with psilocybin. Mystical-like experiences may particularly contribute to ketamine’s immediate and persistent psychiatric benefits.
The Paragaricocrinidae is an enigmatic late Paleozoic family of camerate crinoids that retained a robustly constructed calyx more typical of Devonian to Early Mississippian crinoids. The discovery of the oldest member of this family, Tuscumbiacrinus madisonensis n. gen. n. sp., initiated a phylogenetic investigation of the Paragaricocrinidae and consideration of its diversification and paleobiogeographic distribution. Phylogenetic analyses demonstrate the need to describe Tuscumbiacrinus n. gen and conduct revisions to preexisting taxa, resulting in the description of Palenciacrinus mudaensis n. gen. n. sp.; Pulcheracrinus n. gen.; Nipponicrinus hashimotoi n. gen. n. sp.; and Nipponicrinus akiyoshiensis n. gen. n. sp. Megaliocrinus exotericus Strimple is reassigned to Pulcheracrinus n. gen. In addition to having an anachronistic morphology, relatively few specimens are known through the ca. 76-million-year duration of this family. This pattern is unlikely to have resulted from low fossil sampling alone, and instead likely reflects low abundance and/or taxonomic richness of a long-lived waning clade. From its apparent origination in Laurussia during the Mississippian, the Paragaricocrinidae diversified into a cosmopolitan clade. Following a diversity drop during the Pennsylvanian, the Paragaricocrinidae persisted but exemplified characteristics of a dead clade walking until its eventual extinction during the middle Permian (Wordian).
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Migrants often experience psychological distress due to pre-, peri- and post-migration stressors. Scalable interventions like Doing What Matters in Times of Stress (DWM) and Problem Management Plus (PM+) have been developed to address these challenges. This study evaluates a stepped-care program combining DWM and PM+ for migrants in Italy, examining its context, implementation, and mechanisms of impact. A mixed-methods process evaluation was conducted alongside a randomized controlled trial (RCT), following the Medical Research Council (MRC) framework. Post-trial qualitative data were collected through individual interviews with intervention participants (n = 10) and stakeholders (n = 10), as well as a focus group with intervention providers (n = 8). Thematic analysis was performed using NVivo. Cultural stigma and practical barriers influenced engagement, while community leaders fostered trust and participation. Interventions were feasible and acceptable. Digital delivery improved accessibility for some but posed challenges for those with low technological literacy or private spaces. The stepped-care approach supported gradual engagement with mental health strategies, enhancing self-care and emotional awareness, while provider relationships were key to sustaining motivation. The stepped-care model alleviated psychological distress and was well-received. Findings underscore the need for cultural sensitivity, digital accessibility and community engagement to optimize migrant mental health support.
The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
In late 2009 Indonesia revived a proposal to build a nuclear power facility on the seismically active Muria Peninsula of north central Java over sustained civil society opposition including the voice of moderate Islam. The following assessment by Richard Tanter, Arabella Imhoff and David Von Hippel poses a range of issues about siting decisions in light of state-society relations and nuclear power feasibility. The issues are as relevant to mature democracies as to “emerging democracies,” as Indonesia is now sometimes styled. Muria poses formidable challenges to Indonesian democracy while posing equally important questions about the nation's developmental trajectory.
The participants at the six-party talks should consider the full scope of activities needed to implement the South Korean scheme; that they should explore an alternative approach that would link the Russian and South Korean grids, thereby achieving the same outcome at lower cost and lesser political risk; and that the six parties should consider adopting a short-term, alternative package rather than resuming HFO deliveries to the DPRK because this approach would provide more energy services, faster, and at lower risk and cost to give immediate substance to statements of longer “term intention to supply assistance to the DPRK. We further suggest that these issues be explored with the North Koreans at the six-party talks at a subsequent technical working group before major commitments are made to proceeding with the South Korean proposal.
Firn can store glacial meltwater and delay contribution to sea level rise, but ice layers and ice slabs within the shallow firn layer can impede the downward percolation of melt. Here we report firn conditions along a transect on southwest Devon Ice Cap (DIC), Nunavut, and explore its response to air temperature variability over a decadal period. We present results from two field campaigns, during which six shallow firn cores were extracted along the same transect in spring 2012 and 2022. At all sites, the ice fraction (IF) was less in 2022 than in 2012, and the firn content increased. Between 2012 and 2022, the IF of the firn layer changed by −30% at the lowest elevation site (1400 m a.s.l.) and by −11% at the highest elevation site (1800 m a.s.l.) and by an average of −26% across all sites. Despite higher annual positive degree day sums during 2012–22 compared to 2002–12, cooler summers in 2013, 2018 and 2021 resulted in less ice content in the shallow firn layer. This demonstrates that the shallow firn layer can regenerate from several cooler years and highlights the nuanced response of the DIC shallow firn layer to climate warming.
Basal channels are incised troughs formed by elevated melt beneath ice shelves. Channels often coincide with shear margins, suggesting feedbacks between channel formation and shear. However, the effect of channel position and shape on ice-shelf flow has not been systematically explored. We use a model to show that, as expected, channels concentrate deformation and increase ice-shelf flow speeds, in some cases by over 100% at the ice-shelf center and over 80% at the grounding line. The resulting increase in shear can cause stresses around the channels to exceed the threshold for failure, suggesting that rifting, calving and retreat might result. However, channels have different effects depending on their width, depth and position on an ice shelf. Channels in areas where ice shelves are spreading freely have little effect on ice flow, and even channels in confined regions of the shelf do not necessarily alter flow significantly. Nevertheless, if located in areas of vulnerability, particularly in the shear margins near the grounding line, melt channels may alter flow in a way that could lead to catastrophic ice-shelf breakup by mechanically separating shelves from their embayments.
Environmental changes can be positive in mental illness. Systematic, planned and guided environmental change in all its aspects is called nidotherapy. It has shown some benefit but has not been extended to whole communities.
Aims
A cluster-randomised step-wedge trial is planned in six village communities in Nottinghamshire, England, covering an adult population of 400.
Method
Adults in six villages will be offered a full personal environmental assessment followed by agreed change in different 3-month periods over the course of 1 year. All six villages have populations between 51 and 100 residents and are similar demographically. Assessments of mental health, personality status, social function, quality of life and environment satisfaction will be made. After the initial baseline period of 3 months, two villages will be randomised to nidotherapy for 3 months, a further two at 6 months and the last two at 9 months.
Results
The primary outcome will be change in social function; secondary outcomes include health-related quality of life, anxiety and depressive symptoms, personality status, costs of nidotherapy and life satisfaction. Adverse events will also be recorded. The analysis will be carried out using a multimodal statistical approach examining (a) the change in scores of the primary outcome (social function); (b) change in scores of all secondary outcomes, including costs; and (c) changes in environmental satisfaction.
Conclusions
The findings of this study should help to determine whether nidotherapy has a place in the early detection and treatment of mental pathology.
Adaptive radiotherapy (ART) is commonly used to mitigate effects of anatomical change during head and neck (H&N) radiotherapy. The process of identifying patients for ART can be subjective and resource-intensive. This feasibility project aims to design and validate a pipeline to automate the process and use it to assess the current clinical pathway for H&N treatments.
Methods:
The pipeline analysed patients’ on-set cone-beam CT (CBCT) scans to identify inter-fractional anatomical changes. CBCTs were converted into synthetic CTs, contours were automatically generated, and the original plan was recomputed. Each synthetic CT was evaluated against a set of dosimetric goals, with failed goals causing an ART recommendation.
To validate pipeline performance, a ‘gold standard’ was synthesised by recomputing patients’ original plans on a rescan-CT acquired during treatment and identifying failed clinical goals. The pipeline sensitivity and specificity compared to this ‘gold standard’ were calculated for 12 ART patients. The pipeline was then run on a cohort of 12 ART and 14 non-ART patients, and its sensitivity and specificity were instead calculated against the clinical decision made.
Results:
The pipeline showed good agreement with the synthesised ‘gold standard’ with an optimum sensitivity of 0·83 and specificity of 0·67. When run over a cohort containing both ART and non-ART patients and assessed against the subjective clinical decision made, the pipeline showed no predictive power (sensitivity: 0·58, specificity: 0·47).
Conclusions:
Good agreement with the ‘gold standard’ gives confidence in pipeline performance and disagreement with clinical decisions implies implementation could help standardise the current clinical pathway.
Maladaptive daydreaming is a distinct syndrome in which the main symptom is excessive vivid fantasising that causes clinically significant distress and functional impairment in academic, vocational and social domains. Unlike normal daydreaming, maladaptive daydreaming is persistent, compulsive and detrimental to one’s life. It involves detachment from reality in favour of intense emotional engagement with alternative realities and often includes specific features such as psychomotor stereotypies (e.g. pacing in circles, jumping or shaking one’s hands), mouthing dialogues, facial gestures or enacting fantasy events. Comorbidity is common, but existing disorders do not account for the phenomenology of the symptoms. Whereas non-specific therapy is ineffective, targeted treatment seems promising. Thus, we propose that maladaptive daydreaming be considered a formal syndrome in psychiatric taxonomies, positioned within the dissociative disorders category. Maladaptive daydreaming satisfactorily meets criteria for conceptualisation as a psychiatric syndrome, including reliable discrimination from other disorders and solid interrater agreement. It involves significant dissociative aspects, such as disconnection from perception, behaviour and sense of self, and has some commonalities with but is not subsumed under existing dissociative disorders. Formal recognition of maladaptive daydreaming as a dissociative disorder will encourage awareness of a growing problem and spur theoretical, research and clinical developments.
Online labor markets have great potential as platforms for conducting experiments. They provide immediate access to a large and diverse subject pool, and allow researchers to control the experimental context. Online experiments, we show, can be just as valid—both internally and externally—as laboratory and field experiments, while often requiring far less money and time to design and conduct. To demonstrate their value, we use an online labor market to replicate three classic experiments. The first finds quantitative agreement between levels of cooperation in a prisoner's dilemma played online and in the physical laboratory. The second shows— consistent with behavior in the traditional laboratory—that online subjects respond to priming by altering their choices. The third demonstrates that when an identical decision is framed differently, individuals reverse their choice, thus replicating a famed Tversky-Kahneman result. Then we conduct a field experiment showing that workers have upward-sloping labor supply curves. Finally, we analyze the challenges to online experiments, proposing methods to cope with the unique threats to validity in an online setting, and examining the conceptual issues surrounding the external validity of online results. We conclude by presenting our views on the potential role that online experiments can play within the social sciences, and then recommend software development priorities and best practices.
To better understand clinicians’ rationale for ordering testing for C. difficile infection (CDI) for patients receiving laxatives and the impact of the implementation of a clinical decision support (CDS) intervention.
Design:
A mixed-methods, case series was performed from March 2, 2017 to December 31, 2018.
Setting:
Yale New Haven Hospital, a 1,541 bed tertiary academic medical center.
Participants:
Hospitalized patients ≥ 18 years old, and clinicians who were alerted by the CDS.
Intervention:
CDS was triggered in real-time when a clinician sought to order testing for CDI for a patient who received one or more doses of laxatives within the preceding 24 hours.
Results:
A total of 3,376 CDS alerts were triggered during the 21-month study period from 2,567 unique clinician interactions. Clinicians bypassed the CDS alert 74.5% of the time, more frequent among residents (48.3% bypass vs. 39.9% accept) and advanced practice providers (APPs) (34.9% bypass vs. 30.6% accept) than attendings (11.3% bypass vs. 22.5% accept). Ordering clinicians noted increased stool frequency/output (48%), current antibiotic exposure (34%), and instructions by an attending physician to test (28%) were among the most common reasons for overriding the alert and proceeding with testing for CDI.
Conclusions:
Testing for CDI despite patient laxative use was associated with an increased clinician concern for CDI, patient risk for CDI, and attending physician instruction for testing. Attendings frequently accepted CDS guidance while residents and APPs often reinstated CDI test orders, suggesting a need for greater empowerment and discretion when ordering tests.
Data from an RCT of IAPT Norway (“Prompt Mental Health Care” [PMHC]) were linked to several administrative registers up to five years following the intervention. The aims were to (1) examine the effects of PMHC compared to treatment-as-usual (TAU) on work-related outcomes and health care use, (2) estimate the cost–benefit of PMHC, and (3) examine whether clinical outcomes at six-month follow-up explained the effects of PMHC on work−/cost–benefit-related outcomes.
Methods
RCTs with parallel assignment were conducted at two PMHC sites (N = 738) during 2016/2017. Eligible participants were considered for admission due to anxiety and/or depression. We used Bayesian estimation with 90% credibility intervals (CI) and posterior probabilities (PP) of effects in favor of PMHC. Primary outcome years were 2018–2022. The cost–benefit analysis estimated the overall economic gain expressed in terms of a benefit–cost ratio and the differences in overall public sector spending.
Results
The PMHC group was more likely than the TAU group to be in regular work without receiving welfare benefits in 2019–2022 (1.27 ≤ OR ≤ 1.43). Some evidence was found that the PMHC group spent less on health care. The benefit–cost ratio in terms of economic gain relative to intervention costs was estimated at 5.26 (90%CI $ - $1.28, 11.8). The PP of PMHC being cost-beneficial for the economy as a whole was 85.9%. The estimated difference in public sector spending was small. PMHC effects on work participation and cost–benefit were largely explained by PMHC effects on mental health.
Conclusions
The results support the societal economic benefit of investing in IAPT-like services.
In July 2022, a genetically linked and geographically dispersed cluster of 12 cases of Shiga toxin-producing Escherichia coli (STEC) O103:H2 was detected by the UK Health Security Agency using whole genome sequencing. Review of food history questionnaires identified cheese (particularly an unpasteurized brie-style cheese) and mixed salad leaves as potential vehicles. A case–control study was conducted to investigate exposure to these products. Case food history information was collected by telephone. Controls were recruited using a market research panel and self-completed an online questionnaire. Univariable and multivariable analyses were undertaken using Firth Logistic Regression. Eleven cases and 24 controls were included in the analysis. Consumption of the brie-style cheese of interest was associated with illness (OR 57.5, 95% confidence interval: 3.10–1,060). Concurrently, the production of the brie-style cheese was investigated. Microbiological sample results for the cheese products and implicated dairy herd did not identify the outbreak strain, but did identify the presence of stx genes and STEC, respectively. Together, epidemiological, microbiological, and environmental investigations provided evidence that the brie-style cheese was the vehicle for this outbreak. Production of unpasteurized dairy products was suspended by the business operator, and a review of practices was performed.
Several methods used to examine differential item functioning (DIF) in Patient-Reported Outcomes Measurement Information System (PROMIS®) measures are presented, including effect size estimation. A summary of factors that may affect DIF detection and challenges encountered in PROMIS DIF analyses, e.g., anchor item selection, is provided. An issue in PROMIS was the potential for inadequately modeled multidimensionality to result in false DIF detection. Section 1 is a presentation of the unidimensional models used by most PROMIS investigators for DIF detection, as well as their multidimensional expansions. Section 2 is an illustration that builds on previous unidimensional analyses of depression and anxiety short-forms to examine DIF detection using a multidimensional item response theory (MIRT) model. The Item Response Theory-Log-likelihood Ratio Test (IRT-LRT) method was used for a real data illustration with gender as the grouping variable. The IRT-LRT DIF detection method is a flexible approach to handle group differences in trait distributions, known as impact in the DIF literature, and was studied with both real data and in simulations to compare the performance of the IRT-LRT method within the unidimensional IRT (UIRT) and MIRT contexts. Additionally, different effect size measures were compared for the data presented in Section 2. A finding from the real data illustration was that using the IRT-LRT method within a MIRT context resulted in more flagged items as compared to using the IRT-LRT method within a UIRT context. The simulations provided some evidence that while unidimensional and multidimensional approaches were similar in terms of Type I error rates, power for DIF detection was greater for the multidimensional approach. Effect size measures presented in Section 1 and applied in Section 2 varied in terms of estimation methods, choice of density function, methods of equating, and anchor item selection. Despite these differences, there was considerable consistency in results, especially for the items showing the largest values. Future work is needed to examine DIF detection in the context of polytomous, multidimensional data. PROMIS standards included incorporation of effect size measures in determining salient DIF. Integrated methods for examining effect size measures in the context of IRT-based DIF detection procedures are still in early stages of development.