529 results
56 Impact of ACTIV-6 treatment on PROMIS-29 at 7, 14, 28, and 90 days
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- Julia Whitman, Mark Sulkowski, Russell Rothman, Chris Lindsell, Jennifer Barrett, Thomas Stewart
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 15
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OBJECTIVES/GOALS: As mortality and morbidity from acute COVID-19 decline, the impact of COVID-19 on short- and long-term quality of life (QoL) becomes critical to address. We assessed the impact of re-purposed COVID-19 therapies on QoL as a secondary outcome measure in ACTIV-6, a decentralized platform trial. METHODS/STUDY POPULATION: Adults aged ≥30 with mild-to-moderate COVID-19 enroll in ACTIV-6 online or through a study site. Patients are randomized to a medication of interest or placebo. Medications are mailed and symptoms are tracked using electronic diaries. QoL is measured#_msocom_1 using the PROMIS-29 questionnaire. Adjusted Bayesian logistic regression models are used to measure effects of treatment on the seven PROMIS-29 QoL domains at days 7, 14, 28#_msocom_2 and 90. Covariates are treatment, age, gender, symptom duration and severity, vaccination status, geographic region, call center#_msocom_3#_msocom_4, and calendar time. Treatment effects are described using ORs, 95% credible intervals, and posterior probabilities of efficacy, P(eff). RESULTS/ANTICIPATED RESULTS: There are 5,362 patients included, representing four of the study arms in ACTIV-6. We report results where P(eff)<0.025 and P(eff)>0.975 in the table below. Table 1. Scale Day: OR* (95% credible interval, P(eff)) Therapy Physical Anxiety Depression Fatigue Sleep Social Pain Ivermectin 400 — Ivermectin 600 D7: 0.77 (0.61-0.96, 0.01) D14: 0.65 (0.49-0.85, <0.01) D28: 0.69 (0.52-0.92, 0.01) — D7: 0.79 (0.64-0.97, 0.01) — D14 0.78 (0.60-1.00, 0.02) D28: 0.66 (0.50-0.87, <0.01) Fluticasone - D14: 0.77 (0.60-0.99, 0.02) — D7: 0.76 (0.62-0.93, <0.01) D90: 0.79 (0.64-0.98, 0.01) — D7: 0.74 (0.59-0.93, 0.01) Fluvoxamine D7: 0.66 (0.51-0.84, 0.01) — D28: 1.38 (1.02, 1.85, 0.98) D7: 0.78 (0.63-0.97, 0.01) D7: 0.77 (0.62-0.95, 0.01) — *OR > 1 favors active intervention DISCUSSION/SIGNIFICANCE: Results suggest fluvoxamine may improve depression scores by day 28, while placebo is favored in several other scales across treatments. Differences between treatment and placebo are not seen at most other timepoints. This trial is ongoing and future work will include results from additional ACTIV-6 study arms.
COVID-19 passenger screening to reduce travel risk and translocation of disease
- Lindsay L. Waite, Ahmad Nahhas, Jan Irvahn, Grace Garden, Caroline M. Kerfonta, Elizabeth Killelea, William Ferng, Joshua J. Cummins, Rebecca Mereness, Thomas Austin, Stephen Jones, Nels Olson, Mark Wilson, Benson Isaac, Craig A. Pepper, Iain S. Koolhof, Jason Armstrong
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- Journal:
- Epidemiology & Infection / Volume 152 / 2024
- Published online by Cambridge University Press:
- 08 February 2024, e36
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Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.
Replies to commentaries on beyond playing 20 questions with nature
- Abdullah Almaatouq, Thomas L. Griffiths, Jordan W. Suchow, Mark E. Whiting, James Evans, Duncan J. Watts
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- Journal:
- Behavioral and Brain Sciences / Volume 47 / 2024
- Published online by Cambridge University Press:
- 05 February 2024, e65
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Commentaries on the target article offer diverse perspectives on integrative experiment design. Our responses engage three themes: (1) Disputes of our characterization of the problem, (2) skepticism toward our proposed solution, and (3) endorsement of the solution, with accompanying discussions of its implementation in existing work and its potential for other domains. Collectively, the commentaries enhance our confidence in the promise and viability of integrative experiment design, while highlighting important considerations about how it is used.
Chapter 45 - Case Study 1: Caring for Teams – An Organisation-Wide Approach to Wellbeing, Psychosocial Care, and Mental Healthcare
- from Section 5 - Sustaining and Caring for Staff During Emergencies
- Edited by Richard Williams, University of South Wales, Verity Kemp, Independent Health Emergency Planning Consultant, Keith Porter, University of Birmingham, Tim Healing, Worshipful Society of Apothecaries of London, John Drury, University of Sussex
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- Major Incidents, Pandemics and Mental Health
- Published online:
- 11 January 2024
- Print publication:
- 01 February 2024, pp 337-344
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Summary
This case study illustrates approaches to promoting the wellbeing of and initiating psychosocial care to support the mental health of the staff of public sector services in the UK. It focuses on staff who work in emergencies, including in the fire and rescue, police, ambulance, and search and rescue services, often referred to in the UK as the Blue Light services. This case study provides information illustrating what can be done to assist the work of employing organisations to promote the mental health of all employees – that is, senior, middle, junior, general, and professional managers and their staff. It describes important concepts in planning and in delivering interventions.
Description of the Public Safety Medical Response and Patient Encounters Within and During the Indianapolis (USA) Spring 2020 Civil Unrest
- Thomas P. Arkins, Mark Liao, Daniel O’Donnell, Nancy Glober, Gregory Faris, Elizabeth Weinstein, Michael W. Supples, Julia Vaizer, Benton R. Hunter, Thomas Lardaro
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- Journal:
- Prehospital and Disaster Medicine / Volume 39 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 25 January 2024, pp. 73-77
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- February 2024
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Objective:
This study describes the local Emergency Medical Services (EMS) response and patient encounters corresponding to the civil unrest occurring over a four-day period in Spring 2020 in Indianapolis, Indiana (USA).
Methods:This study describes the non-conventional EMS response to civil unrest. The study included patients encountered by EMS in the area of the civil unrest occurring in Indianapolis, Indiana from May 29 through June 1, 2020. The area of civil unrest defined by Indianapolis Metropolitan Police Department covered 15 blocks by 12 blocks (roughly 4.0 square miles) and included central Indianapolis. The study analyzed records and collected demographics, scene times, interventions, dispositions, EMS clinician narratives, transport destinations, and hospital course with outcomes from receiving hospitals for patients extracted from the area of civil unrest by EMS.
Results:Twenty-nine patients were included with ages ranging from two to sixty-eight years. In total, EMS transported 72.4% (21 of 29) of the patients, with the remainder declining transport. Ballistic injuries from gun violence accounted for 10.3% (3 of 29) of injuries. Two additional fatalities from penetrating trauma occurred among patients without EMS contact within and during the civil unrest. Conditions not involving trauma occurred in 37.9% (11 of 29). Among transported patients, 33.3% (7 of 21) were admitted to the hospital and there was one fatality.
Conclusions:While most EMS transports did not result in hospitalization, it is important to note that the majority of EMS calls did result in a transport. There was a substantial amount of non-traumatic patient encounters. Trauma in many of the encounters was relatively severe, and the findings imply the need for rapid extraction methods from dangerous areas to facilitate timely in-hospital stabilization.
Scoping article: research frontiers on the governance of the Sustainable Development Goals
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- Thomas Hickmann, Frank Biermann, Carole-Anne Sénit, Yixian Sun, Magdalena Bexell, Mitzi Bolton, Basil Bornemann, Jecel Censoro, Aurelie Charles, Dominique Coy, Frederik Dahlmann, Mark Elder, Felicitas Fritzsche, Thiago Gehre Galvão, Jarrod Grainger-Brown, Cristina Inoue, Kristina Jönsson, Montserrat Koloffon Rosas, Kerstin Krellenberg, Enayat Moallemi, Ivonne Lobos Alva, Shirin Malekpour, Dianty Ningrum, Aneliya Paneva, Lena Partzsch, Rodrigo Ramiro, Rob Raven, Eszter Szedlacsek, John Thompson, Melanie van Driel, Jéssica Viani Damasceno, Robert Webb, Sabine Weiland
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- Journal:
- Global Sustainability / Volume 7 / 2023
- Published online by Cambridge University Press:
- 24 January 2024, e7
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Non-Technical Summary
This article takes stock of the 2030 Agenda and focuses on five governance areas. In a nutshell, we see a quite patchy and often primarily symbolic uptake of the global goals. Although some studies highlight individual success stories of actors and institutions to implement the goals, it remains unclear how such cases can be upscaled and develop a broader political impact to accelerate the global endeavor to achieve sustainable development. We hence raise concerns about the overall effectiveness of governance by goal-setting and raise the question of how we can make this mode of governance more effective.
Technical SummaryA recent meta-analysis on the political impact of the Sustainable Development Goals (SDGs) has shown that these global goals are moving political processes forward only incrementally, with much variation across countries, sectors, and governance levels. Consequently, the realization of the 2030 Agenda for Sustainable Development remains uncertain. Against this backdrop, this article explores where and how incremental political changes are taking place due to the SDGs, and under what conditions these developments can bolster sustainability transformations up to 2030 and beyond. Our scoping review builds upon an online expert survey directed at the scholarly community of the ‘Earth System Governance Project’ and structured dialogues within the ‘Taskforce on the SDGs’ under this project. We identified five governance areas where some effects of the SDGs have been observable: (1) global governance, (2) national policy integration, (3) subnational initiatives, (4) private governance, and (5) education and learning for sustainable development. This article delves deeper into these governance areas and draws lessons to guide empirical research on the promises and pitfalls of accelerating SDG implementation.
Social Media SummaryAs SDG implementation lags behind, this article explores 5 governance areas asking how to strengthen the global goals.
The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis
- Zeynep Akcaoglu, Thomas Vaessen, Eva Velthorst, Ginette Lafit, Robin Achterhof, Barnaby Nelson, Patrick McGorry, Frederike Schirmbeck, EU-GEI High Risk Study, Craig Morgan, Jessica Hartmann, Mark van der Gaag, Lieuwe de Haan, Lucia Valmaggia, Philip McGuire, Matthew Kempton, Henrietta Steinhart, Annelie Klippel, Wolfgang Viechtbauer, Tim Batink, Ruud van Winkel, Thérèse van Amelsvoort, Machteld Marcelis, Evelyne van Aubel, Ulrich Reininghaus, Inez Myin-Germeys
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 05 January 2024, pp. 1-9
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Background
Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis.
MethodsWe used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models.
ResultsSI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs.
ConclusionsOur results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.
Low-Temperature Hydrothermal Alteration of Trachybasalt at Conical Seamount, Papua New Guinea: Formation of Smectite and Metastable Precursor Phases
- Giovanna Giorgetti, Thomas Monecke, Reinhard Kleeberg, Mark D. Hannington
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- Journal:
- Clays and Clay Minerals / Volume 57 / Issue 6 / December 2009
- Published online by Cambridge University Press:
- 01 January 2024, pp. 725-741
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The conversion of volcanic glass to secondary alteration products is one of the most common mineralogical transformations during low-temperature hydrothermal alteration of submarine basalts. To better understand the mechanism and kinetics of this transformation, porphyritic and formerly glassy trachybasalt, recovered from Conical Seamount, Papua New Guinea, was studied in detail. Low-temperature interaction of trachybasalt with hydrothermal fluids at this submerged volcano occurred in response to the formation of submarine epithermal-style gold mineralization. Alteration of the coherent volcanic rocks is heterogeneous with pronounced differences in alteration intensity occurring between igneous minerals and the surrounding glassy groundmass. In comparison to the volcanic glass, the crystalline phases were less prone to hydrothermal alteration with the alteration susceptibility decreasing from clinopyroxene through biotite to feldspar. Low-temperature alteration of clinopyroxene resulted in the formation of abundant saponite-like smectite with no topotactic relationship being observed between the two phases. In contrast, the conversion of biotite to smectite involved structural inheritance as the orientation of common structural blocks was maintained during alteration. Transmission and analytical electron microscopy revealed that pervasive alteration of interstitial glass in the groundmass of the trachybasalt resulted in the formation of montmorillonite- and saponite-like smectite whereby smectite composition is strongly influenced by the glass chemistry. The occurrence of poorly crystalline domains with a 0.3 to 0.4 nm layer spacing in the altered interstitial glass suggests that the transformation of glass to smectite involved the formation of a transitional alteration product. Comparison with the results of previous studies highlights the fact that the glass-to-smectite transformation can proceed through more than one reaction pathway. Reaction style and reaction progress are controlled by kinetic factors such as the mode of fluid transport triggering alteration in the low-temperature hydrothermal environment. Alteration of the trachybasalt at Conical Seamount is inferred to have taken place at a comparably low fluid-rock ratio as the low permeability and the absence of primary fractures and joints restricted fluid circulation through the coherent volcanic rocks.
Low-Temperature Hydrothermal Alteration of Silicic Glass at the PACMANUS Hydrothermal Vent Field, Manus Basin: An XRD, SEM and AEM-TEM study
- Glovanna Glorgetti, Thomas Monecke, Reinhard Kleeberg, Mark D. Hannington
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- Journal:
- Clays and Clay Minerals / Volume 54 / Issue 2 / April 2006
- Published online by Cambridge University Press:
- 01 January 2024, pp. 240-251
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Dacitic lava recovered from the immediate subsurface of the submarine PACMANUS hydrothermal vent field exhibits variable degrees of hydrothermal alteration resulting from the interaction of the glassy volcanic rocks with mineralizing hydrothermal fluids at relatively low temperatures. Transmission electron microscopic (TEM) investigations revealed that the felsic volcanic glass transformed to nm-thick smectitic flakes of the montmorillonite-beidellite series via a dissolution and reprecipitation mechanism. The process of smectite formation did not proceed through X-ray amorphous or poorly crystalline transitional phases. Alteration of the glass was found to be most pronounced adjacent to perlitic cracks and vesicles that form an interconnected network focusing fluid flow. Glass dissolution adjacent to these fluid pathways resulted in a characteristic alteration texture at the nm scale; the intensely altered groundmass contains round cavities that are partially coated or filled by smectitic flakes. The Mg content of the smectite broadly increases towards the fluid pathways. Smectitic flakes with compositions corresponding to saponite occur in the intensely altered groundmass adjacent to perlitic cracks. In addition, anatase, apatite and rare kaolinite were formed during the alteration of the volcanic glass. Primary minerals including plagioclase show only minor textural evidence of alteration. However, some primary plagioclase laths show X-ray amorphous rims depleted in Na, Ca and Al. The TEM investigations of the dacitic lava samples from the PACMANUS vent field demonstrate that volcanic glass has a higher susceptibility to hydrothermal alteration at low temperatures than most associated primary phases. The findings of the study suggest that the interaction between the volcanic rock and the hydrothermal fluids proceeded under open-system conditions leading to a mobilization of alkali elements and a redistribution of Ti at the nm scale. The Mg required for the formation of trioctahedral smectite was supplied by the hydrothermal fluids.
2 Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes
- Kelsey R Thomas, Katherine J Bangen, Alexandra J Weigand, Gema Ortiz, Kayla S Walker, David P Salmon, Mark W Bondi, Emily C Edmonds
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 103-104
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Objective:
There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of <129 across subgroups.
Participants and Methods:A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score <129, by cluster group.
Results:Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p<.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p<.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score <129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p<.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p<.001) groups at greater risk of progression to a DRS score <129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS <129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).
Conclusions:Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.
6 Pulse Pressure and APOE ε4 Dose Interact to Affect Cerebral Blood Flow in Older Adults Without Dementia
- Lauren Edwards, Kelsey R Thomas, Alexandra J Weigand, Emily C Edmonds, Alexandra L Clark, Einat K Brenner, Daniel A Nation, Lisa Delano-Wood, Mark W Bondi, Katherine J Bangen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 107-108
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Objective:
Alterations in cerebral blood flow (CBF) are associated with risk of cognitive decline and Alzheimer’s disease (AD). Although apolipoprotein E (APOE) ε4 and greater vascular risk burden have both been linked to reduced CBF in older adults, less is known about how APOE ε4 status and vascular risk may interact to influence CBF. We aimed to determine whether the effect of vascular risk on CBF varies by gene dose of APOE ε4 alleles (i.e., number of e4 alleles) in older adults without dementia.
Participants and Methods:144 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent arterial spin labeling (ASL) and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure assessment. Vascular risk was assessed using pulse pressure (systolic blood pressure -diastolic blood pressure), which is thought to be a proxy for arterial stiffening. Participants were classified by number of APOE ε4 alleles (n0 alleles = 87, m allele = 46, n2 alleles = 11). CBF in six FreeSurfer-derived a priori regions of interest (ROIs) vulnerable to AD were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regression models tested the interaction between categorical APOE ε4 dose (0, 1, or 2 alleles) and continuous pulse pressure on CBF in each ROI, adjusting for age, sex, cognitive diagnosis (cognitively unimpaired vs. mild cognitive impairment), antihypertensive medication use, cerebral metabolism (FDG-PET composite), reference CBF region (precentral gyrus), and AD biomarker positivity defined using the ADNI-optimized phosphorylated tau/ß-amyloid ratio cut-off of > 0.0251 pg/ml.
Results:A significant pulse pressure X APOE ε4 dose interaction was found on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex (ps < .005). Among participants with two e4 alleles, higher pulse pressure was significantly associated with lower CBF (ps < .001). However, among participants with zero or one ε4 allele, there was no significant association between pulse pressure and CBF (ps > .234). No significant pulse pressure X APOE ε4 dose interaction was found in the inferior temporal cortex, rostral middle frontal gyrus, or medial orbitofrontal cortex (ps > .109). Results remained unchanged when additionally controlling for general vascular risk assessed via the modified Hachinski Ischemic Scale.
Conclusions:These findings demonstrate that the cross-sectional association between pulse pressure and region-specific CBF differs by APOE ε4 dose. In particular, a detrimental effect of elevated pulse pressure on CBF in AD-vulnerable regions was found only among participants with the e4/e4 genotype. Our findings suggest that pulse pressure may play a mechanistic role in neurovascular unit dysregulation for those genetically at greater risk for AD. Given that pulse pressure is just one of many potentially modifiable vascular risk factors for AD, future studies should seek to examine how these other factors (e.g., diabetes, high cholesterol) may interact with APOE genotype to affect cerebrovascular dysfunction.
17 Education Moderates the Association Between Hippocampal CBF and Memory in Women but Not Men
- Einat K Brenner, Alexandra J Weigand, Lauren C Edwards, Amanda T Calcetas, Maria Bordyug, Sarah J Banks, Erin E Sundermann, Kelsey R Thomas, Mark W Bondi, Katherine J Bangen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 227-228
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Objective:
Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.
Participants and Methods:Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.
Results:CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.
Conclusions:These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.
5 From Advantage to Disadvantage: Women’s Clinical Trajectory in Early-Stage Alzheimer’s Disease
- Erin E. Sundermann, Sarah J. Banks, Mark W. Bondi, Anat Biegon, Thomas Hildebrandt
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 101-102
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Objective:
There are critical and perplexing sex/gender differences in Alzheimer’s disease (AD). Women show a more favorable clinical profile in preclinical AD particularly with verbal memory, but a steeper decline post mild cognitive impairment (MCI) diagnosis and, ultimately, higher rates of AD. Longitudinal studies are needed to understand sex differences across the AD trajectory. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we identified profiles of memory trajectories among those with evidence of preclinical AD or MCI at baseline and how these trajectories differ by sex.
Participants and Methods:In our sample of 659 participants (age range: 55-90, mean age=72.9 [SD=7.4], 95% non-Hispanic White; mean follow-up=41.2 [SD=32.3] months), 233 were labelled “preclinical” AD (51% women) at baseline based on a cognitively normal status but positivity for either the cerebrospinal fluid p-Tau/Aß42, Amyloid PET or Tau PET biomarkers, and 426 participants (44% women) were MCI at baseline based on Jak/Bondi criteria. We applied latent class growth curve modeling to the heterogeneous change in the Rey Auditory Verbal Learning Test (RAVLT) Immediate and Delayed Recall within preclinical and MCI groups separately. Models in MCI group included Non-Linear Spline to account for differential change rates within subgroups. Models were compared on Bayesian Information Criterion, Entropy, and Class distribution to determine a best-fitting model. Effects of sex on trajectories were the primary outcomes. All models included APOE4 carrier status and age.
Results:Women outperformed men on Immediate and Delayed Recall at baseline in the preclinical and MCI groups (ps<.05). Within the preclinical group, 3-class models representing stable, decline, and accelerated decline provided optimal fit for both Immediate and Delayed Recall. Whereas, on average, preclinical women showed more stable Immediate Recall than men (beta=6.24, SE=.82, p<.0001), they were more likely to be in the Immediate Recall accelerated decline class (23.4% vs. 16.25%; female:male; Chi-square=36.29, p<.00001). On average, preclinical women and men did not differ in Delayed Recall trajectories (beta=.31, SE=.30, p=.28); however, preclinical women were more likely to be in the stable Delayed Recall class (11.04% vs. 6.5%; Chi-Square=19.19, p<.0001). Within the MCI group, 2-class models representing a stable decline group and an accelerated decline group provided optimal fit for both outcomes. Whereas, on average, MCI women showed more stable Immediate Recall than men (beta=3.55, SE=.79, p<.0001), they were more likely to be in the Immediate Recall accelerated decline class, although not significantly. Women and men did not differ, on average, in their Delayed Recall trajectories; however, women were significantly more likely to be in the Delayed Recall accelerated decline class (Chi-square=32.24, p<.0001).
Conclusions:Our findings indicate that sex is an important determinant of the variability observed in early-stage AD trajectories; however, sex differences varied by Immediate versus Delayed Recall likely due, in-part, to psychometric test properties. Our results suggest that, when looking at sex differences in AD trajectories on average, women’s superior stability in verbal learning masks their higher likelihood of rapid decline. Our findings have implications for our ability to optimally diagnose and track disease progression in both sexes.
Copilots for Linguists
- AI, Constructions, and Frames
- Tiago Timponi Torrent, Thomas Hoffmann, Arthur Lorenzi Almeida, Mark Turner
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- Published online:
- 20 December 2023
- Print publication:
- 01 February 2024
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- Element
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AI can assist the linguist in doing research on the structure of language. This Element illustrates this possibility by showing how a conversational AI based on a Large Language Model (AI LLM chatbot) can assist the Construction Grammarian, and especially the Frame Semanticist. An AI LLM chatbot is a text-generation system trained on vast amounts of text. To generate text, it must be able to find patterns in the data and mimic some linguistic capacity, at least in the eyes of a cooperative human user. The authors do not focus on whether AIs “understand” language. Rather, they investigate whether AI LLM chatbots are useful tools for linguists. They reframe the discussion from what AI LLM chatbots can do with language to what they can do for linguists. They find that a chatty LLM can labor usefully as an eliciting interlocutor, and present precise, scripted routines for prompting conversational LLMs.
OP58 Challenges In Maintaining Up To Date Health Technology Assessments in Rare Diseases: Lessons From Fabry Disease In Australia
- Kathleen Nicholls, Charles Denaro, Michel Tchan, Carolyn Ellaway, Drago Bratkovic, Hazel Palmer, Sheridan Campbell, Megan Fookes, Mark Thomas
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- Journal:
- International Journal of Technology Assessment in Health Care / Volume 39 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 14 December 2023, p. S16
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Introduction
Fabry disease is a rare, inherited X-linked lysosomal storage disease characterized by a wide spectrum of heterogeneously progressive clinical phenotypes, and which results in progressive kidney disease, cardiomyopathy, cerebrovascular disease, and reduced life expectancy. Disease-specific therapy aims to improve symptoms, stabilize current disease and delay progression. In Australia treatment access requires that patients meet pre-specified criteria, which have been in place for more than 15 years. Patient questions prompted the patient organization, Fabry Australia, to investigate why these criteria had remained unchanged despite significant progress in the understanding and management of Fabry disease.
MethodsA panel comprising two members of Fabry Australia and its Medical Advisory Committee conducted a review of the literature. The aim of this was to inform the clinical quality of the Australian treatment access criteria with reference to international guidelines and contemporary data. The findings from the literature were applied to develop consensus recommendations for classification and Fabry-specific treatment initiation criteria in diagnosed patients.
ResultsEvidence supports earlier treatment with reduced barriers to access in some circumstances. Australian access criteria are misaligned with this. They do not distinguish between classical and non-classical Fabry phenotypes, neglect the impact of quality of life and gastrointestinal symptoms, and impose symptom-severity related criteria, which may lead to unnecessary treatment initiation delay. An updated framework is presented. It differentiates phenotypes, facilitates more timely access to Fabry-specific treatment for classical males, and supports relevant organ involvement criteria in classical females and patients with non-classical disease.
ConclusionsA well-performing health technology assessment system facilitates patient access to cost-effective treatments that improve health outcomes. Timely treatment initiation is important to avoid irreversible organ damage in Fabry patients. Patients’ questions about out-dated access criteria has prompted research and uncovered barriers that are no longer clinically valid. The perspectives of the patient as a stakeholder in their disease management should not be overlooked when assessing the value of health technologies in the rare disease setting.
Ten new insights in climate science 2023
- Mercedes Bustamante, Joyashree Roy, Daniel Ospina, Ploy Achakulwisut, Anubha Aggarwal, Ana Bastos, Wendy Broadgate, Josep G. Canadell, Edward R. Carr, Deliang Chen, Helen A. Cleugh, Kristie L. Ebi, Clea Edwards, Carol Farbotko, Marcos Fernández-Martínez, Thomas L. Frölicher, Sabine Fuss, Oliver Geden, Nicolas Gruber, Luke J. Harrington, Judith Hauck, Zeke Hausfather, Sophie Hebden, Aniek Hebinck, Saleemul Huq, Matthias Huss, M. Laurice P. Jamero, Sirkku Juhola, Nilushi Kumarasinghe, Shuaib Lwasa, Bishawjit Mallick, Maria Martin, Steven McGreevy, Paula Mirazo, Aditi Mukherji, Greg Muttitt, Gregory F. Nemet, David Obura, Chukwumerije Okereke, Tom Oliver, Ben Orlove, Nadia S. Ouedraogo, Prabir K. Patra, Mark Pelling, Laura M. Pereira, Åsa Persson, Julia Pongratz, Anjal Prakash, Anja Rammig, Colin Raymond, Aaron Redman, Cristobal Reveco, Johan Rockström, Regina Rodrigues, David R. Rounce, E. Lisa F. Schipper, Peter Schlosser, Odirilwe Selomane, Gregor Semieniuk, Yunne-Jai Shin, Tasneem A. Siddiqui, Vartika Singh, Giles B. Sioen, Youba Sokona, Detlef Stammer, Norman J. Steinert, Sunhee Suk, Rowan Sutton, Lisa Thalheimer, Vikki Thompson, Gregory Trencher, Kees van der Geest, Saskia E. Werners, Thea Wübbelmann, Nico Wunderling, Jiabo Yin, Kirsten Zickfeld, Jakob Zscheischler
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- Journal:
- Global Sustainability / Volume 7 / 2023
- Published online by Cambridge University Press:
- 01 December 2023, e19
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Non-technical summary
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summaryThe Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summaryWe highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
6 - A Critical Analysis of Past and Present Campaigns to Challenge Online Racism in English Professional Football
- Edited by Imran Awan, Birmingham City University, Irene Zempi, Nottingham Trent University
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- Book:
- Hate Crime in Football
- Published by:
- Bristol University Press
- Published online:
- 03 April 2024
- Print publication:
- 13 November 2023, pp 83-102
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Summary
Introduction
Inside Wembley Stadium, the men’s England manager, Gareth Southgate, huddles his players together for a final team talk before the players step up to take their penalty kicks. First for England is Harry Kane, who scores with a shot that is low and to the goalkeeper’s right. Next is Harry Maguire, who smashes the ball into the top right of the goal. However, Marcus Rashford hits the post and Jadon Sancho’s and Bukayo Saka’s efforts are saved by Italian goalkeeper Gianluigi Donnarumma. It is the final of the UEFA (Union of European Football Associations) European Football Championship (Euro 2020), held in July 2021 due to the COVID-19 pandemic, and England have been defeated on penalties. Sadly, the online racist abuse which followed soured what should have been a proud moment for English football, as the national men’s team had reached their first major tournament final since 1966.
After the penalty kicks, in the ensuing moments online, the three young England players who missed theirs were rendered Black and ‘foreign’ above anything else, thereby exposing people’s deeply held views concerning race relations. Of particular interest here is the fact that a Fédération Internationale de Football Association (FIFA) report released in June 2022 highlighted that more than a third of the online abuse during the final came from online accounts based in the United Kingdom (UK). To offer further context, the abuse mirrored online reactions a decade prior towards Black English players Ashley Cole and Ashley Young, who also missed penalties against Italy during Euro 2012 (Press Association, 2012). The Euro 2020 case illustrates both the ease with which online racism is expressed and its frequency – it sadly represents yet another chapter in the history of online racism within football. What is clear is that forms of hate and forms of racism are evolving, with much of this moving online. Indeed, while racist chants and insults, and even bananas, were once hurled at players inside football stadiums, we can now observe these epithets in multiple digital forms. Many strategies (past and present) have sought to challenge online racism in football, some being more effective than others.
Reciprocal relationships between stress and depressive symptoms: the essential role of the nucleus accumbens
- Yizhou Ma, Peter Kochunov, Mark D. Kvarta, Tara LeGates, Bhim M. Adhikari, Joshua Chiappelli, Andrew van der Vaart, Eric L. Goldwaser, Heather Bruce, Kathryn S. Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E. Nichols, L. Elliot Hong
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- Journal:
- Psychological Medicine / Volume 54 / Issue 5 / April 2024
- Published online by Cambridge University Press:
- 26 September 2023, pp. 1045-1056
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Background
Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.
MethodsIn total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006–2010, age = 55.0 ± 7.5 [40–70] years; second visit: 2014–2019; age = 62.7 ± 7.5 [44–80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes.
ResultsLongitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = −0.032 to −0.023, p = 0.006–0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7–14.3%, p < 0.001−p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10−5) in participants with high v. no SLEs.
ConclusionsThe nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.
Mindfulness training and exercise differentially impact fear extinction neurocircuitry
- Shaked E. Leibovitz, Gunes Sevinc, Jonathan Greenberg, Britta Hölzel, Tim Gard, Thomas Calahan, Mark Vangel, Scott P. Orr, Mohammed R. Milad, Sara W. Lazar
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- Journal:
- Psychological Medicine / Volume 54 / Issue 4 / March 2024
- Published online by Cambridge University Press:
- 01 September 2023, pp. 835-846
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Background
The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program.
MethodsWe investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27).
ResultsThe groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement.
ConclusionsOur results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.
Healthcare staff mental health trajectories during the COVID-19 pandemic: findings from the COVID-19 Staff Wellbeing Survey
- Julie-Ann Jordan, Ciaran Shannon, Dympna Browne, Emma Carroll, Jennifer Maguire, Keith Kerrigan, Sinead Hannan, Thomas McCarthy, Mark A. Tully, Ciaran Mulholland, Kevin F. W. Dyer
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- Journal:
- BJPsych Open / Volume 9 / Issue 4 / July 2023
- Published online by Cambridge University Press:
- 22 June 2023, e112
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Background
Cross-sectional studies have shown that the COVID-19 pandemic has had a significant impact on the mental health of healthcare staff. However, it is less well understood how working over the long term in successive COVID-19 waves affects staff well-being.
AimsTo identify subpopulations within the health and social care staff workforce with differentiated trajectories of mental health symptoms during phases of the COVID-19 pandemic.
MethodThe COVID-19 Staff Wellbeing Survey assessed health and social care staff well-being within an area of the UK at four time points, separated by 3-month intervals, spanning November 2020 to August 2021.
ResultsGrowth mixture models were performed on the depression, anxiety and post-traumatic stress disorder longitudinal data. Two class solutions provided the best fit for all models. The vast majority of the workforce were best represented by the low-symptom class trajectory, where by symptoms were consistently below the clinical cut-off for moderate-to-severe symptoms. A sizable minority (13–16%) were categorised as being in the high-symptom class, a group who had symptom levels in the moderate-to-severe range throughout the peaks and troughs of the pandemic. In the depression, anxiety and post-traumatic stress disorder models, the high-symptom class perceived communication from their organisation to be less effective than the low-symptom class.
ConclusionsThis research identified a group of health service staff who reported persistently high mental health symptoms during the pandemic. This group of staff may well have particular needs in terms of the provision of well-being support services.