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Ectoparasite and bacterial population genetics and community structure indicate extent of bat movement across an island chain
- Clifton D. McKee, Alison J. Peel, David T. S. Hayman, Richard Suu-Ire, Yaa Ntiamoa-Baidu, Andrew A. Cunningham, James L. N. Wood, Colleen T. Webb, Michael Y. Kosoy
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- Parasitology / Accepted manuscript
- Published online by Cambridge University Press:
- 24 May 2024, pp. 1-53
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53 2-Back Performance Does Not Differ Between Cognitive Training Groups in Older Adults Without Dementia
- Nicole D Evangelista, Jessica N Kraft, Hanna K Hausman, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Cheshire Hardcastle, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric Porges, Adam J Woods
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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. 360-361
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Objective:
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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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. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
2 Higher White Matter Hyperintensity Load Adversely Affects Pre-Post Proximal Cognitive Training Performance in Healthy Older Adults
- Emanuel M Boutzoukas, Andrew O’Shea, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Hanna K Hausman, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Samantha G Smith, Hyun Song, Eric C Porges, Alex Hishaw, Steven T DeKosky, Samuel S Wu, Michael Marsiske, Gene E Alexander, Ronald Cohen, Adam J Woods
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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. 671-672
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Objective:
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
1 Task-Based Functional Connectivity and Network Segregation of the Useful Field of View (UFOV) fMRI task
- Jessica N Kraft, Hanna K Hausman, Cheshire Hardcastle, Alejandro Albizu, Andrew O’Shea, Nicole D Evangelista, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Eric Porges, Adam J Woods
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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. 606-607
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Objective:
Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.
Participants and Methods:336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.
Results:ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).
Conclusions:To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.
78 BVMT-R Learning Ratio Moderates Cognitive Training Gains in Useful Field of View Task in Healthy Older Adults
- Cheshire Hardcastle, Jessica N. Kraft, Hanna K. Hausman, Andrew O’Shea, Alejandro Albizu, Nicole D. Evangelista, Emanuel Boutzoukas, Emily J. Van Etten, Pradyumna K. Bharadwaj, Hyun Song, Samantha G. Smith, Eric Porges, Steven DeKosky, Georg A. Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E. Alexander, Adam J. Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 180-181
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Objective:
Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there is variability in the level of cognitive gains after cognitive training across studies. One potential explanation for this variability could be moderating factors. Prior studies suggest variables moderating cognitive training gains share features of the training task. Learning trials of the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) recruit similar cognitive abilities and have overlapping neural correlates with the UFOV task and speed-ofprocessing/working memory tasks and therefore could serve as potential moderators. Exploring moderating factors of cognitive training gains may boost the efficacy of interventions, improve rigor in the cognitive training literature, and eventually help provide tailored treatment recommendations. This study explored the association between the HVLT-R and BVMT-R learning and the UFOV task, and assessed the moderation of HVLT-R and BVMT-R learning on UFOV improvement after a 3-month speed-ofprocessing/attention and working memory cognitive training intervention in cognitively healthy older adults.
Participants and Methods:75 healthy older adults (M age = 71.11, SD = 4.61) were recruited as part of a larger clinical trial through the Universities of Florida and Arizona. Participants were randomized into a cognitive training (n=36) or education control (n=39) group and underwent a 40-hour, 12-week intervention. Cognitive training intervention consisted of practicing 4 attention/speed-of-processing (including the UFOV task) and 4 working memory tasks. Education control intervention consisted of watching 40-minute educational videos. The HVLT-R and BVMT-R were administered at the pre-intervention timepoint as part of a larger neurocognitive battery. The learning ratio was calculated as: trial 3 total - trial 1 total/12 - trial 1 total. UFOV performance was measured at pre- and post-intervention time points via the POSIT Brain HQ Double Decision Assessment. Multiple linear regressions predicted baseline Double Decision performance from HVLT-R and BVMT-R learning ratios controlling for study site, age, sex, and education. A repeated measures moderation analysis assessed the moderation of HVLT-R and BVMT-R learning ratio on Double Decision change from pre- to post-intervention for cognitive training and education control groups.
Results:Baseline Double Decision performance significantly associated with BVMT-R learning ratio (β=-.303, p=.008), but not HVLT-R learning ratio (β=-.142, p=.238). BVMT-R learning ratio moderated gains in Double Decision performance (p<.01); for each unit increase in BVMT-R learning ratio, there was a .6173 unit decrease in training gains. The HVLT-R learning ratio did not moderate gains in Double Decision performance (p>.05). There were no significant moderations in the education control group.
Conclusions:Better visuospatial learning was associated with faster Double Decision performance at baseline. Those with poorer visuospatial learning improved most on the Double Decision task after training, suggesting that healthy older adults who perform below expectations may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes.
6 Adjunctive Transcranial Direct Current Stimulation and Cognitive Training Alters Default Mode and Frontoparietal Control Network Connectivity in Older Adults
- Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Emanuel M Boutzoukas, Andrew O’Shea, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Eric S Porges, Georg A Hishaw, Samuel Wu, Steven DeKosky, Gene E Alexander, Michael Marsiske, Ronald A Cohen, Adam J Woods
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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. 675-676
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Objective:
Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.
Participants and Methods:This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.
Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.
Results:Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.
Conclusions:These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
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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. 527-528
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Objective:
Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
The Role of Social Defeat in Neurological differences in Psychotic Patients
- A. Malaviya, P. A. Lalousis, S. J. Wood, A. Bertolino, S. B. Borgwardt, P. Brambilla, J. Kambeitz, R. Lencer, C. Pantelis, S. Ruhrmann, R. K. Salokangas, F. Schultze-Lutter, E. Meisenzahl, N. Koutsouleris, R. Upthegrove
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S183
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Introduction
The social defeat hypothesis (SDH) suggests that a chronic experience of social defeat increases the likelihood of the development of psychosis. The SDH indicates that a negative experience of exclusion leads to an increase in the baseline activity of the mesolimbic dopamine system (MDS), which in turn leads to the onset of psychosis. Social defeat models have previously been produced using animal models and preclinical literature; however, these theories have not fully been tested in human clinical samples. There have been studies implying changes in brain structure due to social defeat interactions; however, research evidence is varied.
ObjectivesThis study aims to uncover whether exposure to SoDe has an impact on brain structure. Furthermore, we hope to understand if these changes are relevant to other mental health disorders.
Methods698 (506 no SoDe, 191 SoDe) participants between the ages of 15-41 were recruited from the PRONIA-FP7 study. SoDe was measured from the self-reported questionnaires’ Bullying Scale’ and ‘The Everyday Discrimination Scale’. T1-weighted structural MRI data were processed; five 2 sample t-test analyses were carried out to compare the GMV differences in the entire sample and between the four groups.
ResultsThe VBM analysis showed significant group interactions in the right thalamus proper when comparing participants who had experience SoDe to participants who had not experienced SoDe including all 4 groups along with left cerebral white matter differences. In the ROP subgroup, significant group interactions in the left cerebellum white matter were found along with right cerebral white matter, left cerebral white matter and right Thalamus proper.
ConclusionsThe findings suggest that there are significant group interactions in thalamus and cerebral white matter. This is in keeping with some previous research suggesting volumetric changes in the thalamus due to stress and psychosis. Similarly for white matter there is some evidence suggesting differences due to SoDe and psychosis. However, there is a scarcity of research in this area with different research suggesting distinctive findings and therefore the evidence is inconclusive. In the ROP group analysis significant group interactions were present in the cerebellum due to SoDe experience. There is research suggesting the cerebellum’s role in multiple different aspects like social interaction, higher-order cognition, working memory, cognitive flexibility, and psychotic symptoms, with every research suggesting multiple different things the role of the cerebellum in SoDe in the ROP population is in question. Nonetheless this large-scale research presents some interesting novel finding and leads the way to a new area of research. Further analysis will explore the relationship between groups on markers of stress (CRP) and neuroinflammation as potential mediation of the environmental effects of SoDe.
Disclosure of InterestNone Declared
Dynamics and risk of transmission of bovine tuberculosis in the emerging dairy regions of Ethiopia
- G. A. Mekonnen, A. J. K. Conlan, S. Berg, B. T. Ayele, A. Mihret, A. Olani, H. Asgedom, The ETHICOBOTS consortium , J. L. N. Wood, G. Ameni
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- Epidemiology & Infection / Volume 149 / 2021
- Published online by Cambridge University Press:
- 24 February 2021, e69
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The Ethiopian government has several initiatives to expand and intensify the dairy industry; however, the risk of bovine tuberculosis (bTB) spread is a challenge. To assess the rate of expansion and risk factors for transmission of bTB within-herds, we carried out a repeated cross-sectional survey at two time points, 2016/17 and 2018, in three regional cities, namely, Gondar, Hawassa and Mekelle, representing the emerging dairy belts of Ethiopia. The total number of herds involved was 128, comprising an average of 2303 cattle in each round. The Single Intradermal Comparative Cervical Tuberculin (SICCT) test was used to identify reactor status and data on herd-level risk factors were collected using a structured questionnaire. In the first survey, the apparent prevalence of bTB, as measured by the SICCT test, was 4.5% (95% CI 3.7–5.4%) at the individual animal-level and 24% (95% CI 17.5–32%) at the herd-level. There was no statistically significant change in the overall apparent prevalence or regional distribution at the second survey, consistent with the infection being endemic. The incidence rate was estimated at 3.6 (95% CI 2.8–4.5) and 6.6 (95% CI 3.0–12.6) cases/100 cattle (or herd)-years at the animal- and herd-levels, respectively. Risk factors significantly associated with the within-herd transmission of bTB were age group and within-herd apparent prevalence at the start of the observation period. We noted that farmers voluntarily took steps to remove reactor cattle from their herds as a consequence of the information shared after the first survey. Removal of reactors between surveys was associated with a reduced risk of transmission within these herds. However, with no regulatory barriers to the sale of reactor animals, such actions could potentially lead to further spread between herds. We therefore advocate the importance of setting up regulations and then establishing a systematic bTB surveillance programme to monitor the impact prior to implementing any control measures in Ethiopia.
Dysphagia presentation and management following coronavirus disease 2019: an acute care tertiary centre experience
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- C Dawson, R Capewell, S Ellis, S Matthews, S Adamson, M Wood, L Fitch, K Reid, M Shaw, J Wheeler, P Pracy, P Nankivell, N Sharma
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- Journal:
- The Journal of Laryngology & Otology / Volume 134 / Issue 11 / November 2020
- Published online by Cambridge University Press:
- 10 November 2020, pp. 981-986
- Print publication:
- November 2020
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Objectives
As the pathophysiology of Covid-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital.
ResultsDuring the first wave of the Covid-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status.
ConclusionDysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with Covid-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.
LO83: Effect of the transition to an entrustability scale on assessor stringency and leniency on daily encounter cards in emergency medicine
- S. Dewhirst, W. Cheung, N. Dudek, T. Wood, J. Frank
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 22 / Issue S1 / May 2020
- Published online by Cambridge University Press:
- 13 May 2020, p. S37
- Print publication:
- May 2020
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Introduction: Workplace based assessments (WBAs) are integral to emergency medicine residency training. However many biases undermine their validity, such as an assessor's personal inclination to rate learners leniently or stringently. Outlier assessors produce assessment data that may not reflect the learner's performance. Our emergency department introduced a new Daily Encounter Card (DEC) using entrustability scales in June 2018. Entrustability scales reflect the degree of supervision required for a given task, and are shown to improve assessment reliability and discrimination. It is unclear what effect they will have on assessor stringency/leniency – we hypothesize that they will reduce the number of outlier assessors. We propose a novel, simple method to identify outlying assessors in the setting of WBAs. We also examine the effect of transitioning from a norm-based assessment to an entrustability scale on the population of outlier assessors. Methods: This was a prospective pre-/post-implementation study, including all DECs completed between July 2017 and June 2019 at The Ottawa Hospital Emergency Department. For each phase, we identified outlier assessors as follows: 1. An assessor is a potential outlier if the mean of the scores they awarded was more than two standard deviations away from the mean score of all completed assessments. 2. For each assessor identified in step 1, their learners’ assessment scores were compared to the overall mean of all learners. This ensures that the assessor was not simply awarding outlying scores due to working with outlier learners. Results: 3927 and 3860 assessments were completed by 99 and 116 assessors in the pre- and post-implementation phases respectively. We identified 9 vs 5 outlier assessors (p = 0.16) in the pre- and post-implementation phases. Of these, 6 vs 0 (p = 0.01) were stringent, while 3 vs 5 (p = 0.67) were lenient. One assessor was identified as an outlier (lenient) in both phases. Conclusion: Our proposed method successfully identified outlier assessors, and could be used to identify assessors who might benefit from targeted coaching and feedback on their assessments. The transition to an entrustability scale resulted in a non-significant trend towards fewer outlier assessors. Further work is needed to identify ways to mitigate the effects of rater cognitive biases.
LO75: Does the Ottawa emergency department shift observation tool give more useful information – assessing the utility of transitioning to a novel, entrustability based assessment tool in the emergency department
- S. Dewhirst, W. Cheung, N. Dudek, T. Wood, J. Frank
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 22 / Issue S1 / May 2020
- Published online by Cambridge University Press:
- 13 May 2020, p. S34
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- May 2020
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Introduction: The Ottawa Emergency Department Shift Observation Tool (O-EDShOT) was recently developed to assess a resident's ability to safely run an ED shift and is supported by multiple sources of validity evidence. The O-EDShOT uses entrustability scales, which reflect the degree of supervision required for a given task. It was found to discriminate between learners of different levels, and to differentiate between residents who were rated as able to safely run the shift and those who were not. In June 2018 we replaced norm-based daily encounter cards (DECs) with the O-EDShOT. With the ideal assessment tool, most of the score variability would be explained by variability in learners’ performances. In reality, however, much of the observed variability is explained by other factors. The purpose of this study is to determine what proportion of total score variability is accounted for by learner variability when using norm-based DECs vs the O-EDShOT. Methods: This was a prospective pre-/post-implementation study, including all daily assessments completed between July 2017 and June 2019 at The Ottawa Hospital ED. A generalizability analysis (G study) was performed to determine what proportion of total score variability is accounted for by the various factors in this study (learner, rater, form, pgy level) for both the pre- and post- implementation phases. We collected 12 months of data for each phase, because we estimated that 6-12 months would be required to observe a measurable increase in entrustment scale scores within a learner. Results: A total of 3908 and 3679 assessments were completed by 99 and 116 assessors in the pre- and post- implementation phases respectively. Our G study revealed that 21% of total score variance was explained by a combination of post-graduate year (PGY) level and the individual learner in the pre-implementation phase, compared to 59% in the post-implementation phase. An average of 51 vs 27 forms/learner are required to achieve a reliability of 0.80 in the pre- and post-implementation phases respectively. Conclusion: A significantly greater proportion of total score variability is explained by variability in learners’ performances with the O-EDShOT compared to norm-based DECs. The O-EDShOT also requires fewer assessments to generate a reliable estimate of the learner's ability. This study suggests that the O-EDShOT is a more useful assessment tool than norm-based DECs, and could be adopted in other emergency medicine training programs.
Long-term outcomes of ADHD: Global and regional study publication trends
- M. Shaw, H. Caci, P. Hodgkins, J. Kahle, N. Callamaras, A. Woods
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- Journal:
- European Psychiatry / Volume 26 / Issue S2 / March 2011
- Published online by Cambridge University Press:
- 16 April 2020, p. 578
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Introduction
As awareness of ADHD has increased throughout the world, interest has grown beyond the constellation of ADHD symptoms, including long-term effects and impact on people's lives.
ObjectivesTo examine the consequences of childhood ADHD and the relevance of these outcomes in different world regions.
AimsThis analysis examined the publication trends of studies of long-term outcomes of ADHD over time and among world regions.
MethodsStudy identification followed Cochrane guidelines. Twelve databases were searched for reports published in English 1980–2010. Limiting criteria were designed to maximize study inclusion while maintaining a high level of study rigor: the studies were to
(1) be peer-reviewed,
(2) be primary study reports,
(3) include a comparator group or baseline, and
(4) report outcome results measured for a mean of 8 years (prospective studies, range of all studies was 6 months-40 years) after the start of the study, in late adolescence, or adulthood.
The fully-defined electronic search yielded 4615 citations, which were then reviewed manually based on the titles and abstracts, yielding a final of 371 studies.
ResultsStudy publication trends analysed included: publication year, country and world region of origin, outcome types, and study types. In general, the numbers of studies published per year globally has increased substantially (from 2 in 1980 to more than 40/year in 2007 and 2008) with differences observed between Europe and North America.
ConclusionsAnalysis of publication trends can provide insight into outcomes of ADHD and the focus of specific world regions.
Supported by Shire Development Inc.
Review of studies of ADHD: Long-term outcomes with and without treatment
- M. Shaw, H. Caci, P. Hodgkins, J. Kahle, N. Callamaras, A. Woods
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- Journal:
- European Psychiatry / Volume 26 / Issue S2 / March 2011
- Published online by Cambridge University Press:
- 16 April 2020, p. 579
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Introduction
As awareness of ADHD has increased worldwide, interest has grown beyond the constellation of ADHD symptoms, to include long-term impact on people's lives and society in general.
ObjectivesExamine the results of studies of long-term life consequences of ADHD.
AimsTo identify areas of life affected long-term by ADHD and differences in outcomes with and without ADHD treatment.
MethodsFollowing Cochrane guidelines, 12 databases were searched for studies published in English (1980–2010). Limiting criteria maximized study inclusion while maintaining high study rigor: (1) peer-reviewed, (2) primary study reports, (3) including a comparator condition, and (4) reporting long-term outcomes (mean 8 years, range 6 months-40 years from study start for prospective studies; subjects in adolescence or adulthood for retrospective or cross-sectional studies). The fully-defined electronic search yielded 4615 citations. Manual review based on titles and abstracts yielded 340 studies included in this analysis of outcomes.
ResultsThe majority of studies (86%, 243 of 281; studies of untreated ADHD only) showed that untreated ADHD has substantial negative long-term outcomes, encompassing nine broad-ranging areas of life: non-medicinal drug use/addictive behaviour, antisocial behaviour, academic achievement, occupational achievement, public services use, self-esteem, social function, obesity, and driving outcomes. In contrast, most studies including ADHD pharmacotherapy and/or non-pharmacotherapy (94%, 46 of 49) showed that compared with baseline or untreated ADHD, long-term outcomes improved or stabilized with treatment of ADHD.
ConclusionsADHD has notable negative long-term consequences, and this negative impact may be reduced with treatment of ADHD. Supported by Shire Development Inc.
EPA-1671 – Diagnosing Schizophrenia Using Neuroimaging: A Meta-analysis of Multivariate Pattern Recognition Studies
- J. Kambeitz, L. Kambeitz-Ilankovic, S. Leucht, S. Wood, C. Davatzikos, B. Malchow, P. Falkai, N. Koutsouleris
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- Journal:
- European Psychiatry / Volume 29 / Issue S1 / 2014
- Published online by Cambridge University Press:
- 15 April 2020, pp. 1-2
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Background
Numerous studies have applied novel multivariate statistical approaches to the analysis of brain alterations in patients with schizophrenia. However the diagnostic accuracy of the reported predictive models differs largely, making it difficult to evaluate the overall potential of these studies to inform clinical diagnosis.
MethodsWe conducted a comprehensive literature search to identify all studies reporting performance of neuroimaging-based multivariate predictive models for the differentiation of patients with schizophrenia from healthy control subjects. The robustness of the results as well as the effect of potentially confounding continous variables (e.g. age, gender ratio, year of publication) was investigated.
ResultsThe final sample consisted of n=37 studies studies including n=1491 patients with schizophrenia and n=1488 healthy controls. Metaanalysis of the complete sample showed a sensitivity of 80.7% (95%-CI: 77.0 to 83.9%) and a specificity of 80.2% (95%-CI: 83.3 to 76.7%). Separate analysis for the different imaging modalities showed similar diagnostic accuracy for the structural MRI studies (sensitivity 77.3%, specificity 78.7%), the fMRI studies (sensitivity 81.4%, specificity 82.4%) and resting-state fMRI studies (sensitivity 86.9%, specificity 80.3%). Moderator analysis showed significant effects of age of patients on sensitivity (p=0.021) and of positive-tonegative symptom ratio on specificity (p=0.028) indicating better diagnostic accuracy in older patients and patients with positive symptoms.
DiscussionOur analysis indicate an overall sensitivity and overall specificity of around 80 % of neuroimaging-based predictive models for differentiating schizophrenic patients from healthy controls. The results underline the potential applicability of neuroimaging-based predictive models for the diagnosis of schizophrenia.
A systematic review and network meta-analysis of injectable antibiotic options for the control of bovine respiratory disease in the first 45 days post arrival at the feedlot
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- A. M. O'Connor, D. Hu, S. C. Totton, N. Scott, C. B. Winder, B. Wang, C. Wang, J. Glanville, H. Wood, B. White, R. Larson, C. Waldner, J. M. Sargeant
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- Journal:
- Animal Health Research Reviews / Volume 20 / Issue 2 / December 2019
- Published online by Cambridge University Press:
- 21 February 2020, pp. 163-181
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We conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.
A systematic review and network meta-analysis of bacterial and viral vaccines, administered at or near arrival at the feedlot, for control of bovine respiratory disease in beef cattle
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- A. M. O'Connor, D. Hu, S. C. Totton, N. Scott, C. B. Winder, B. Wang, C. Wang, J. Glanville, H. Wood, B. White, R. Larson, C. Waldner, J. M. Sargeant
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- Journal:
- Animal Health Research Reviews / Volume 20 / Issue 2 / December 2019
- Published online by Cambridge University Press:
- 21 February 2020, pp. 143-162
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Vaccination against putative causal organisms is a frequently used and preferred approach to controlling bovine respiratory disease complex (BRD) because it reduces the need for antibiotic use. Because approximately 90% of feedlots use and 90% of beef cattle receive vaccines in the USA, information about their comparative efficacy would be useful for selecting a vaccine. We conducted a systematic review and network meta-analysis of studies assessing the comparative efficacy of vaccines to control BRD when administered to beef cattle at or near their arrival at the feedlot. We searched MEDLINE, MEDLINE In-Process, MEDLINE Daily Epub Ahead of Print, AGRICOLA, Cambridge Agricultural and Biological Index, Science Citation Index, and Conference Proceedings Citation Index – Science and hand-searched the conference proceedings of the American Association of Bovine Practitioners and World Buiatrics Congress. We found 53 studies that reported BRD morbidity within 45 days of feedlot arrival. The largest connected network of studies, which involved 17 vaccine protocols from 14 studies, was included in the meta-analysis. Consistent with previous reviews, we found little compelling evidence that vaccines used at or near arrival at the feedlot reduce the incidence of BRD diagnosis.
Co-occurrence of autistic and psychotic traits: implications for depression, self-harm and suicidality
- Katie N. Sampson, Rachel Upthegrove, Ahmad Abu-Akel, Sayeed Haque, Stephen J. Wood, Renate Reniers
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- Journal:
- Psychological Medicine / Volume 51 / Issue 8 / June 2021
- Published online by Cambridge University Press:
- 21 February 2020, pp. 1364-1372
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Background
There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality.
MethodsCross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed.
ResultsA positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits.
ConclusionsThis study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.
Q fever seroprevalence in Australia suggests one in twenty people have been exposed
- H. F. Gidding, C. Q. Peng, S. Graves, P. D. Massey, C. Nguyen, J. Stenos, H. E. Quinn, P. B. McIntyre, D. N. Durrheim, N. Wood
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- Journal:
- Epidemiology & Infection / Volume 148 / 2020
- Published online by Cambridge University Press:
- 05 February 2020, e18
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Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.