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AVATAR therapy, a digitally supported intervention, utilises avatars to promote recovery in people who experience distressing auditory hallucinations. This approach was recently evaluated in a multicentre randomised controlled trial comparing brief (AV-BRF) and extended (AV-EXT) forms of therapy with treatment as usual (TAU). There was evidence for the effectiveness of therapy, particularly for AV-EXT. However, value for money needs to be assessed.
Aims
To compare separately the cost utility of the brief and extended forms of AVATAR therapy with TAU.
Method
In a three-arm randomised controlled trial the use of health services was measured, and costs (2021/2022; pounds sterling) calculated from a health and social care perspective over a 28-week follow-up period. Quality-adjusted life years (QALYs; derived from the 5-level version of the EuroQol 5-Dimension questionnaire) were combined with costs.
Results
AV-BRF resulted in extra costs of £319 (95% CI, −£1558 to £2496), and AV-EXT in lower costs of £1965 (95% CI, −£1912 to £1519), compared with TAU. Over the follow-up, AV-BRF resulted in 0.0159 (95% CI, −0.0103 to 0.0422) and AV-EXT in 0.0173 (95% CI, −0.0049 to 0.0395) more QALYs than TAU. The cost per QALY for AV-BRF compared with TAU was £20 016, while AV-EXT dominated TAU (lower costs and more QALYs).
Conclusions
Neither version of AVATAR had a substantial impact on QALYs. However, AV-EXT did result in reduced care costs − albeit not statistically significant − and was potentially cost-effective compared with TAU. AV-BRF had an incremental cost-effectiveness ratio that indicated lower potential cost-effectiveness. These findings are uncertain, but could still inform decision-making regarding interventions in this field.
We review the ambiguous legacy of Emil Kraepelin. He established an approach that secured psychiatry’s place as a medical specialty, and his methodology has dominated the profession and defined its long 20th century, 1899–2026. However, his eugenic views weigh heavily because of the catastrophes in which German psychiatry was implicated and to which it contributed actively during the Nazi era that followed. Furthermore, his project to establish mental illness in the form of discrete natural kinds has failed in the light of scientific progress. Psychiatry must embrace the complexity of mental illness and engage more deeply with the inherently fuzzy realms of language, culture, technological change and political power. This shift should bear more strongly on psychiatry’s curriculum, research priorities, continuing professional development, practice, ethics and public engagement.
Sharing, harmonizing, and analyzing participant-level data is of central importance in the rapid research response to emerging pathogens. Individual participant data meta-analyses (IPD-MAs), which synthesize participant-level data from related primary studies, have several advantages over pooling study-level effect estimates in a traditional meta-analysis. IPD-MAs enable researchers to more effectively separate spurious heterogeneity related to differences in measurement from clinically relevant heterogeneity from differences in underlying risk or distribution of factors that modify disease progression. This tutorial describes the steps needed to conduct an IPD-MA of an emerging pathogen and how IPD-MAs of emerging pathogens differ from those of well-studied exposures and outcomes. We discuss key statistical issues, including participant- and study-level missingness and complex measurement error, and present recommendations. We review how IPD-MAs conducted during the COVID-19 response addressed these statistical challenges when harmonizing and analyzing participant-level data related to an emerging pathogen. The guidance presented here is based on lessons learned in our conduct of IPD-MAs in the research response to emerging pathogens, including Zika virus and COVID-19.
This research examines in detail the complex nonlinear forces generated when steep waves interact with vertical cylindrical structures, such as those typically used as offshore wind turbine foundations. These interactions, particularly the nonlinear wave forces associated with the secondary load cycle, present unanswered questions about how they are triggered. Our experimental campaigns underscore the occurrence of the secondary load cycle. We also investigate how the vertical distributions of the scattering force, pressure field and wave field affect the nonlinear wave forces associated with the secondary load cycle phenomena. A phase-based harmonic separation method isolates harmonic components of the scattering force’s vertical distribution, pressure field and wave field. This approach facilitates the clear separation of individual harmonics by controlling the phase of incident waves, which offers new insights into the mechanisms of the secondary load cycle. Our findings highlight the importance of complex nonlinear wave–structure interactions in this context. In certain wave regimes, nonlinear forces are locally larger than the linear forces, highlighting the need to consider the secondary load cycle in structural design. In addition, a novel discovery emerges from our comparative analysis, whereby very high-frequency (over the fifth in harmonic and order) oscillations, strongly correlated to wave steepness, have the potential to play a role in structural fatigue. This new in-depth analysis provides a unique insight regarding the complex interplay between severe waves and typical cylindrical offshore structures, adding to our understanding of the secondary load cycle for applications related to offshore wind turbine foundations.
Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.
Depressive symptoms are common in mild cognitive impairment (MCI). These may be associated with poorer cognitive function and increased risks of dementia transition.
Aims
We aimed to examine the cognitive patterns associated with variations in depressive symptoms in neurodegenerative MCI without a primary mood disorder.
Method
Individuals with MCI (n = 123), including MCI due to Alzheimer’s disease (n = 54) and MCI with Lewy bodies (n = 69), underwent repeated annual assessment of cognitive function and concurrent depressive symptoms using the Addenbrooke’s Cognitive Examination-Revised and the Geriatric Depression Scale-15, respectively.
Between- and within-person differences in depressive symptoms were disaggregated and related to between- and within-person cognitive differences and modification of cognitive performance trajectories over time.
Results
There was strong evidence of a state-based association between depressive symptoms and cognitive function. Intra-individual differences in depressive symptoms were negatively associated with concurrent cognitive performance such that a 2-point increase in depressive score explained a 1-point decrease in cognitive score, on average (point estimate −0.56, 95% credibile interval (CrI) −1.05 to −0.08).
The data did not support a trait-based association between depressive symptoms and cognitive performance (point estimate 0.10, 95% CrI −0.42 to 0.59), nor any between- or within-person trajectory modification associated with depressive symptoms.
Conclusions
Within-person variations in depressive symptom severity are associated with acute cognitive performance differences. Cognitive scores derived during active depressive periods may underestimate longer-term cognitive capabilities. Treating depressive symptoms in MCI may clarify underlying cognitive performance capacity, and help maintain optimal cognitive function for longer.
The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.
Aims
To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.
Method
We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.
Results
Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.
Conclusions
Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
A dramatic increase of small (“arrow-sized”) points, typically beginning after about 2,000 years ago (depending on locality), has often been characterized as marking the introduction of the bow and arrow throughout the Americas, eventually replacing earlier dart-and-atlatl weaponry in most areas. We analyze a large point assemblage from sites in the central Willamette Valley of western Oregon with a 6,000-year-long cultural record. We easily sorted the assemblage into small (“arrow-sized”) and large (“dart-sized”) sets using standard metrics, but we noted extreme temporal overlap, suggesting that (1) atlatls and bows continued in regular use as companion weapons; (2) both large and small projectile tips were affixed to arrows, depending on the target; or (3) there was some combination of these factors. Given the range of point forms, it appears that some served specialized functions (e.g., social conflict, hunting conditions, prey type), suggesting that the uses of stone-tipped weaponry may be more nuanced than has generally been acknowledged. Consequently, we find that assigning points to specific weapon systems requires assumptions we cannot support.
Mild cognitive impairment with Lewy bodies (MCI-LB) may be identified prospectively based on the presence of cognitive impairment and several core clinical features (visual hallucinations, cognitive fluctuations, parkinsonism, and REM sleep behavior disorder). MCI-LB may vary in its presenting features, which may reflect differences in underlying pathological pattern, severity, or comorbidity.
We aimed to assess how clinical features of MCI-LB accumulate over time, and whether this is associated with the rate of cognitive decline.
Methods
In this cohort study, 74 individuals seen with MCI-LB prospectively underwent repeated annual cognitive and clinical assessment up to nine years. Relationships between clinical features (number of core features present and specific features present) and cognitive change on the Addenbrooke’s Cognitive Examination–Revised (ACE-R) were examined with time-varying mixed models. The accumulation of core clinical features over time was examined with a multi-state Markov model.
Results
When an individual with MCI-LB endorsed more clinical features, they typically experienced a faster cognitive decline (ACE-R Score Difference β = −1.1 [−1.7 to −0.5]), specifically when experiencing visual hallucinations (β = −2.1 [−3.5 to −0.8]) or cognitive fluctuations (β = −3.4 [−4.8 to −2.1]).
Individuals with MCI-LB typically acquired more clinical features with the passage of time (25.5% [20.0–32.0%] one-year probability), limiting the prognostic utility of baseline-only features.
Conclusions
The clinical presentation of MCI-LB may evolve over time. The accumulation of more clinical features of Lewy body disease, in particular visual hallucinations and cognitive fluctuations, may be associated with a worse prognosis in clinical settings.
Our overall goal was to enhance the usability and interactivity of the RE-AIM website (re-aim.org) and improve resources to support the application of the RE-AIM framework within the context of dissemination & implementation (D&I) research and practice.
Methods:
We applied a mixed-methods approach to obtain user feedback from 24 D&I researchers and practitioners. Usability (System Usability Scale) and interactivity (Interactivity Scale) were assessed through validated surveys, at baseline and after two iterative rounds of website modifications (Phase 1 and Phase 2). We also conducted qualitative assessments at each phase.
Results:
Qualitative baseline and Phase 1 findings indicated a need to simplify organization, enhance information accessibility, provide concrete guidance on applying RE-AIM, and clarify contextual factors related to RE-AIM constructs. After streamlining website and homepage organization, Phase 2 qualitative results suggested improved user navigation experience; users also requested greater interactivity. Modifications included: new interactive planning tool and a video introduction of contextual factors influencing RE-AIM outcomes. Significant improvements were found in the SUS score from baseline to Phase 1(64.2[SD18.7] to 80.8 [SD 12.1] (p < .05) and remained higher in Phase 2(77.1[SD 15] (p = 0.08). Interactivity also improved from baseline to Phase 2(3.5[SD1.2] to 41[0.9], though not statistically significant.
Conclusion:
User-centered feedback on online resources, as exemplified by this use case example of enhancements to the RE-AIM website, are important in bridging the gap between research and practice, and the revised website should be more accessible and useful to users.
A diagnostic label can have harms and benefits, particularly when provided following routine health screening tests. Whether these are discussed in clinical encounters is unknown.
Aims
To investigate whether potential impacts of diagnostic labelling are discussed before routine screening for non-cancer health conditions and explore the perceived value of such discussions by general practitioners (GPs) and healthcare consumers.
Method
Eleven semi-structured interviews with GPs and two focus groups with eight consumers were conducted. Interviews and focus groups were audio-recorded, transcribed and analysed using thematic analysis methods based on framework analysis.
Results
Prior to routine screening, most GPs did not discuss the potential consequences of diagnostic labelling, and no consumer recalled discussions of this nature. In contrast, many GPs provided information regarding the screening procedure and possible test limitations. Both GPs and consumers identified that it would be valuable to discuss the potential impacts of a diagnostic label; however, preferences varied as to the content and timing (i.e. before or after screening) of this discussion. Six themes that examine the utility of discussing the consequences of diagnostic labelling were identified: patient empowerment, patient variability, condition-specific information, GP and patient interactions and relationship, GP role and responsibilities, and characteristics of screening.
Conclusions
The practice and perceived value of discussing diagnostic labelling consequences were recognised as important by both GPs and consumers. However, preferences regarding the content of discussions and whether these occurred in clinical encounters before or after screening varied.
Objectives/Goals: Injury to the medial knee ligaments (sMCL, dMCL, POL) and anterior cruciate ligament (ACL) can cause anteromedial rotatory instability (AMRI). AMRI can cause knee instability and ACL graft failure, but it is unclear how the sMCL, dMCL, POL, and ACL resist AMRI. We aimed to characterize the in-situ forces of the sMCL, dMCL, POL, and ACL under loading conditions involved with AMRI. Methods/Study Population: We characterized the in situ forces of the sMCL, dMCL, POL, and ACL under 1) isolated external tibial rotation torque (ER), 2) isolated anterior tibial force (Ant), and 3) combined ER+Ant loading. Twenty-eight human cadaveric knees (18 male; mean age, 48±13; 21–65 years) were tested on a robotic manipulator with force sensing. Tibiofemoral kinematics were recorded under isolated ER (4Nm, 0–90°), isolated Ant (134N at 0–90°), and combined ER+Ant (4Nm+100N at 15, 30, 90°). The sMCL, dMCL, POL, and ACL were dissected in random order. The in situ force (N) in the sMCL, dMCL, POL, and ACL at the peak applied load for each loading condition was calculated using superposition and compared with Kruskal–Wallis tests with post hoc pairwise testing using a Bonferroni–Holm correction for multiple comparisons (α = 0.05). Results/Anticipated Results: Under isolated ER, the force in the sMCL (32–52N) from 0°-90° exceeded that of the ACL, dMCL, and POL at each flexion angle (p0.05). Force in the ACL was the second highest (26–6N from 0°-90°). Force in the dMCL and POL was low (≤12N). Under isolated Ant, the ACL carried the highest force at all flexion angles (≥113N) (p0.05), but at 90° the sMCL carried the highest force of all ligaments (p0.05). At 90°, force in the dMCL diminished (Discussion/Significance of Impact: We show that the sMCL is the major stabilizer to external rotation torques and combined anterior and external loading conditions related to anteromedial rotatory instability across the arc of knee flexion, while the dMCL, POL, and ACL play a less prominent role, with the exception of the ACL and dMCL near full extension.
What problem do today’s circuits address? The very general task of improving performance, through the application of negative feedback, of a great many of the circuits we have met to this point.
In our own version of this course, only a minority of the busy students choose to do projects. But a project can be heaps of fun. To help you conceive of one, here is some information on gadgets and ideas that might inspire a project builder, along with sketches of some great projects of yester-term.