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Boundary mixing. Part 2. The impact of ventilation
- Scott W. Li, Andrew W. Woods
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- Journal:
- Journal of Fluid Mechanics / Volume 985 / 25 April 2024
- Published online by Cambridge University Press:
- 22 April 2024, A24
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Through a combination of laboratory experiments and theoretical models, we investigate the interaction of a mean upwelling through a closed basin with a vertical buoyancy flux. The fluid is mixed by a horizontally oscillating rake, which either traverses the whole basin or which oscillates just near one vertical boundary. We first review the steady state and demonstrate that, in both mixing regimes, the vertical density profile across the basin is controlled by the steady-state balance between the upward advective and diffusive fluxes of salinity as described by the classical model introduced by Munk (Deep-Sea Res., vol. 13, issue 4, 1966, pp. 707–730). However, with boundary mixing, we show that both the upwelling and the buoyancy transport are localised to the mixing zone near the boundary, and the interior fluid is stagnant. We then develop a model to describe the transient evolution of the system if there is either a discrete increase or gradual decrease to the buoyancy flux. In the boundary mixing case, the change in the buoyancy flux at the lower boundary leads to a change in the buoyancy of the fluid in the boundary mixing region, and this induces a transient, buoyancy-driven flow in the boundary region in addition to the steady upwelling. In turn, an equal and opposite vertical flow develops in the interior, and this leads to a change in the density stratification of the interior fluid as the system adjusts to a new equilibrium. However, in our experiments, there is no vertical mixing in the interior and interior fluid may upwell or downwell dependent on the change to the buoyancy forcing. We discuss the implications of our results for the transport and mixing in the deep ocean, and the associated interpretation of field experiments.
Challenges and solutions to system-wide use of precision oncology as the standard of care paradigm
- Nesrine Lajmi, Sofia Alves-Vasconcelos, Apostolos Tsiachristas, Andrew Haworth, Kerrie Woods, Charles Crichton, Theresa Noble, Hizni Salih, Kinga A. Várnai, Harriet Branford-White, Liam Orrell, Andrew Osman, Kevin M. Bradley, Lara Bonney, Daniel R. McGowan, Jim Davies, Matthew S. Prime, Andrew Bassim Hassan
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- Journal:
- Cambridge Prisms: Precision Medicine / Volume 2 / 2024
- Published online by Cambridge University Press:
- 26 March 2024, e4
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The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.
Chapter 5 - How Emergencies, Incidents, Disasters, and Disease Outbreaks Affect People and Healthcare Practitioners
- from Section 1 - The Nature and Impacts of Twenty-First-Century Healthcare 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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- Book:
- Major Incidents, Pandemics and Mental Health
- Published online:
- 11 January 2024
- Print publication:
- 01 February 2024, pp 15-22
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Summary
It is usual for humans to experience distress in the aftermath of emergencies, incidents, disasters, and disease outbreaks (EIDD). The manifestation, severity, and duration of the experiences that constitute distress depend on many intrinsic and extrinsic factors. Recent research has demonstrated that distress may be more ubiquitous than was previously thought, and that some interventions, even if well meaning, may not be helpful. Amelioration for most people comes with timely, proportionate, and targeted support and the passage of time. Validation of people’s experiences and minimising the medicalisation of distress are important in helping people to return to ordinary social functioning. This chapter looks at distress related to major events, including the scientific principles, impacts, and implications for intervention. The case study draws on the experience of three members of a pre-hospital team and how a challenging case affected them all.
Chapter 39 - Moral Distress and Moral Injury
- 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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- Book:
- Major Incidents, Pandemics and Mental Health
- Published online:
- 11 January 2024
- Print publication:
- 01 February 2024, pp 287-292
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Summary
This chapter explores the moral dimensions of work in emergency and pre-hospital medicine, with an emphasis on protecting the workforce and maintaining optimal functioning of teams. It explores the concepts of moral distress and moral injury from the literature and as they apply to emergency and pre-hospital medicine, but also in the light of the COVID-19 pandemic. It includes reference to the experience of one helicopter emergency medical service (HEMS) organisation attempting to make changes to its culture.
Chapter 38 - What Ails Professional Responders, and the Implications for Training and Sustaining Healthcare Practitioners
- 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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- Book:
- Major Incidents, Pandemics and Mental Health
- Published online:
- 11 January 2024
- Print publication:
- 01 February 2024, pp 279-286
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There is increasing awareness that working within the field of pre-hospital care can have psychosocial effects on clinicians. This chapter describes a systematic review of current knowledge of the psychosocial consequences of working in pre-hospital care. A considerable amount of research has been conducted, examining in particular whether practitioners develop burnout and psychiatric disorders, especially symptoms of post-traumatic stress and post-traumatic stress disorder (PTSD), as a result of their work. However, most studies did not fully assess whether practitioners developed clinically significant symptoms.. Instead, cross-sectional surveys and self-report questionnaires were used, which considerably overestimate the incidence of these problems. Perhaps the high scores on these questionnaires indicate that practitioners who work in pre-hospital care often suffer considerable stress and distress that can be the result of daily organisational and operational hassles, a high volume of work, lack of resources, and, less than has often been thought, attending unusual and high-profile incidents.
A dynamic model of ${\rm CO}_2$ storage in layered anticlines
- Patrick K. Mortimer, Nicola Mingotti, Andrew W. Woods
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- Journal:
- Journal of Fluid Mechanics / Volume 979 / 25 January 2024
- Published online by Cambridge University Press:
- 18 January 2024, A39
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We explore ${\rm CO}_2$ injection into a layered permeable rock consisting of high permeability reservoir layers, separated by low permeability mudstone, and taking the shape of an anticline within a laterally extensive aquifer. We first show how the storage capacity of the formation depends on the capillary entry pressure of the inter-layer mudstone, so that ${\rm CO}_2$ cannot flow from one layer into the next. We then consider a formation composed of two layers, overlain by a cap rock. For injection into the lowest layer, we show that the injection rate, capillary entry pressure and buoyancy driven flux through the mudstone determine whether the lower or upper layer fills to the spill point first. We also show that at the end of the injection phase, ${\rm CO}_2$ may continue to flow from the lower to the upper layer. This implies that injection should be stopped once the injected volume matches the static capacity of the formation in order to prevent spilling after injection. We present a series of analogue experiments of a two layered system that illustrate some of the principles described by the model, and assess the implications of the results for field scale systems.
1 Sex Differences in Associations Between APOE ε2 and Longitudinal Cognitive Decline
- Madeline Wood, Lisa Xiong, Yuen Yan Wong, Rachel F Buckley, Walter Swardfager, Mario Masellis, Andrew Lim, Emma Nichols, Renaud La Joie, Kaitlin Casaletto, Raj Kumar, Kristen Dams-O’Connor, Priya Palta, Kristen George, Claudia Satizabal, Lisa L Barnes, Julie A Schneider, Judy Pa, Adam Brickman, Sandra Black, Jennifer Rabin
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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. 405-406
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Objective:
Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.
Participants and Methods:We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.
Results:Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.
Conclusions:In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.
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.
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:
- 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.
28 Factor Structure of Conventional Neuropsychological Tests and NIH-Toolbox in Healthy Older Adults
- Kailey Langer, Cheshire Hardcastle, Hanna Hausman, Jessica Kraft, Alejandro Albizu, Nicole Evangelista, Emanuel Boutzoukas, Andrew O’Shea, Emily Van Etten, Samantha Smith, Hyun Song, Pradyumna Bharadwaj, Georg Hishaw, Samuel Wu, Steven DeKosky, Gene Alexander, Eric Porges, Michael Marsiske, Ronald Cohen, Adam 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, p. 710
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Objective:
The National Institutes of Health-Toolbox cognition battery (NIH-TCB) is widely used in cognitive aging studies and includes measures in cognitive domains evaluated for dimensional structure and psychometric properties in prior research. The present study addresses a current literature gap by demonstrating how NIH-TCB integrates into a battery of traditional clinical neuropsychological measures. The dimensional structure of NIH-TCB measures along with conventional neuropsychological tests is assessed in healthy older adults.
Participants and Methods:Baseline cognitive data were obtained from 327 older adults. The following measures were collected: NIH-Toolbox cognitive battery, Controlled Oral Word Association (COWA) letter and animals tests, Wechsler Test of Adult Reading (WTAR), Stroop Color-Word Interference Test, Paced Auditory Serial Addition Test (PASAT), Brief Visuospatial Memory Test (BVMT), Letter-Number Sequencing (LNS), Hopkins Verbal Learning Test (HVLT), Trail Making Test A&B, Digit Span. Hmisc, psych, and GPARotation packages for R were used to conduct exploratory factor analyses (EFA). A 5-factor solution was conducted followed by a 6-factor solution. Promax rotation was used for both EFA models.
Results:The 6-factor EFA solution is reported here. Results indicated the following 6 factors: working memory (Digit Span forward, backward, and sequencing, PASAT trials 1 and 2, NIH-Toolbox List Sorting, LNS), speed/executive function (Stroop color naming, word reading, and color-word interference, NIH-Toolbox Flanker, Dimensional Change, and Pattern Comparison, Trail Making Test A&B), verbal fluency (COWA letters F-A-S), crystallized intelligence (WTAR, NIH-Toolbox Oral Recognition and Picture Vocabulary), visual memory (BVMT immediate and delayed), and verbal memory (HVLT immediate and delayed. COWA animals and NIH-Toolbox Picture Sequencing did not adequately load onto any EFA factor and were excluded from the subsequent CFA.
Conclusions:Findings indicate that in a sample of healthy older adults, these collected measures and those obtained through the NIH-Toolbox battery represent 6 domains of cognitive function. Results suggest that in this sample, picture sequencing and COWA animals did not load adequately onto the factors created from the rest of the measures collected. These findings should assist in interpreting future research using combined NIH-TCB and neuropsychological batteries to assess cognition in healthy older adults.
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.
18 Regional patterns of mitochondrial function using phosphorus magnetic resonance spectroscopy in older adults at-risk for Alzheimer’s disease.
- Francesca V Lopez, Andrew O’Shea, Stacey Alvarez-Alvarado, Adrianna Ratajska, Lauren Kenney, Rachel Schade, Katie Rodriguez, Alyssa Ray, Rebecca O’Connell, Lauren Santos, Emily Van Etten, Hyun Song, Emma Armstrong, Tiffany Gin, Zhiguang Huo, Gene Alexander, Adam J Woods, Dawn Bowers
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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. 331-332
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Objective:
The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.
Participants and Methods:The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.
Results:31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.
Conclusions:Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.
Boundary mixing. Part 1. Transport of buoyancy and passive tracer
- Scott W. Li, Andrew W. Woods
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- Journal of Fluid Mechanics / Volume 976 / 10 December 2023
- Published online by Cambridge University Press:
- 06 December 2023, A23
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Diapycnal mixing plays a key role in the thermohaline circulation of the deep ocean. Field observations have suggested that this mixing is intensified over the rough topography along the boundaries of the ocean. In this study, we experimentally explore the transport of salinity and tracer in a horizontally stirred, stratified fluid with a steady vertical buoyancy flux. The mechanical mixing occurs either uniformly across the tank or near a sidewall. To compare uniform and boundary mixing, first we explore the steady state dynamics and find that, in both cases, the surfaces of constant density are horizontal. With uniform mixing, vertical transport of buoyancy occurs uniformly throughout the tank while, with boundary mixing, transport is confined to the turbulent region and the interior space remains quiescent and does not mix or have any net movement. We then explore the transient evolution of the stratification when the source of buoyancy is removed from the base of the system. In the boundary mixing case, the resulting divergence of the turbulent diffusive flux in the boundary region leads to a reduction in the buoyancy of the fluid in the boundary region, and a net upflow develops in the boundary region. In turn, this drives a downwelling in the interior. Vertical gradients in the rate of downwelling lead to stretching of isopycnals and, together, these processes enable the interior stratification to evolve. The experiments highlight that, with boundary mixing, the main transport of buoyancy occurs near the boundaries even though the interior is stratified; independent measurements of tracer mixing in the interior show that this fluid may be quiescent and stratified even though there is a large flux being transported in the boundary region. This has important implications for the interpretation of mixing data in the ocean. In a companion paper, (Li and Woods Part 2), we explore the interaction of a net upwelling with such boundary mixing.
Gravity-driven flow in a cross-bedded porous rock
- Brian K. Whelan, Andrew W. Woods
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- Journal:
- Journal of Fluid Mechanics / Volume 973 / 25 October 2023
- Published online by Cambridge University Press:
- 23 October 2023, R4
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Many geological layers include cross bedding, which leads to different values for permeability along and across the bedding planes. We explore how such cross bedding impacts buoyancy-driven flow through an inclined aquifer. For each bedding angle and ratio of the permeability along and across the bedding, a free buoyancy-driven plume rises at a particular angle to the horizontal. If the angle of inclination of the aquifer to the horizontal is smaller than this angle, then the plume rises along the upper boundary, otherwise, somewhat surprisingly, the buoyant plume rises along the lower boundary of the aquifer. We present new laboratory experiments to support these predictions. We also test a model for the effective permeabilities which control the speed and the rate of spread of the plume along one or other boundary of the aquifer. We consider the impact of our results for modelling geological storage of ${\rm CO}_2$ or aquifer thermal energy storage.
New Ediacaran biota from the oldest Nama Group, Namibia (Tsaus Mountains), and re-definition of the Nama Assemblage
- Rachel Wood, Fred. T. Bowyer, Ruaridh Alexander, Mariana Yilales, Collen-Issia Uahengo, Kavevaza Kaputuaza, Junias Ndeunyema, Andrew Curtis
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- Journal:
- Geological Magazine / Volume 160 / Issue 9 / September 2023
- Published online by Cambridge University Press:
- 23 October 2023, pp. 1673-1686
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The Nama Group, Namibia (≥550.5 to <538 million years ago, Ma), preserves one of the most diverse metazoan fossil records of the terminal Ediacaran Period. We report numerous features that may be biological in origin from the shallow marine, siliciclastic, lowermost Mara Member (older than ca. 550.5 Ma) from the Tsaus Mountains. These include forms that potentially represent body fossils, Beltanelliformis and an indeterminate juvenile uniterminal rangeomorph or arboreomorph frond, plug trace fossils, Bergaueria, as well as sedimentary surface textures, which are possibly microbially induced. These are the oldest documented macrofossils in the Nama Group. They represent taxa that persist from the Avalon or White Sea assemblages prior to the later appearance of new biota, including calcified metazoans, calcified and soft-bodied tubular taxa including all cloudinids, as well as more complex trace fossils.
Using a new age model that allows more accurate stratigraphic placement of major Ediacaran macrofossil morphogroups and taxa, we propose a re-definition of the Nama Assemblage following the practice for Phanerozoic evolutionary faunas to include only new morphogroups of soft-bodied tubular, calcified taxa and complex trace fossils, defined by first appearance of Cloudina, which postdates deposition of the Kanies and lower Mara members and first appears ca. 550 Ma and persists until at least 539 Ma.
Finally, the Tsaus Mountain environment is pristine, unspoilt by geologists and naturalists. Following World Heritage Convention, we suggest a pledge of non-destructive excavation that all future scientists should be able to make in publications of work that involve research in this area.
Experiments on fluid entrainment and slip in continuous bubble plumes
- Nicola Mingotti, Andrew W. Woods
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- Journal of Fluid Mechanics / Volume 973 / 25 October 2023
- Published online by Cambridge University Press:
- 18 October 2023, A22
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A series of laboratory experiments are reported in which a continuous stream of bubbles rise from a small source at the base of a tank of water. Using different nozzles, bubble sizes $d$ ranging from 1.2 to 11.6 mm were produced for a number of gas volume fluxes, $Q_b$, ranging between 1.1 and $21.1\times 10^{-6}\ {\rm m}^3\ {\rm s}^{-1}$. Within a small distance from the source, the slip speed of these bubbles exceeds the speed of the equivalent single-phase plume with the same buoyancy flux, leading to formation of what we refer to as the ‘slip plume’ regime. Through a combination of high-speed photography, coupled with flow visualisation in the plume and the ambient fluid using dye, we find that the bubble speed and the fluid speed remain nearly constant with height, with the maximum fluid speed being of order $0.30\pm 0.03$ of the bubble speed. Using the filling box method, we also find that the net fluid volume flux in the slip plume increases linearly with distance from the source at a rate $Q_l = \lambda Bz/v_s^2$, where $B$ is the buoyancy flux of the gas, $v_s$ the rise speed of the gas bubbles, $z$ the distance above the source and $\lambda$ is a constant related to the dimensionless volume of fluid in the wake of each bubble. This slip-dominated flow regime can be understood in terms of kinetic energy imparted to the fluid as the bubbles rise and release potential energy. Further experiments with particle-laden plumes illustrate similar scalings for the volume flux in a particle-driven slip plume once the slip speed of the particles exceeds the bulk speed of the equivalent single-phase buoyant plume with the same buoyancy flux. Near the source the slip speed may be smaller than the plume speed, and the flow follows the classical model for a turbulent buoyant plume, with the transition to the slip regime occurring at a distance $z^*\approx (32\pm 5)\lambda ^{3/2} B/v_s^3$ from the source, where the dimensionless parameter $\lambda$ relates to the dimensionless volume of the fluid wake, which we find varies with the Reynolds number of the particles.
Structure and thermal expansion of end-member olivines I: Crystal and magnetic structure, thermal expansion, and spontaneous magnetostriction of synthetic fayalite, Fe2SiO4, determined by high-resolution neutron powder diffraction
- Evangelia K. Tripoliti, David P. Dobson, A. Dominic Fortes, Andrew R. Thomson, Paul F. Schofield, Ian G. Wood
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- Mineralogical Magazine / Volume 87 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 25 August 2023, pp. 789-806
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The lattice parameters and the crystal and magnetic structures of Fe2SiO4 have been determined from 10 K to 1453 K by high-resolution time-of-flight neutron powder diffraction. Fe2SiO4 undergoes two antiferromagnetic phase transformations on cooling from room temperature: the first, at 65.4 K, is to a collinear antiferromagnet with moments on two symmetry-independent Fe ions; the second transition, at ~23 K, is to a structure in which the moments on one of the sets of Fe ions (those on the ‘M1 site’) become canted. The magnetic unit cell is identical to the crystallographic (chemical) unit cell and the space group remains Pbnm throughout. The magnetic structures have been refined and the results found to be in good agreement with previous studies; however, we have determined the spontaneous magnetostrictive strains, which have not been reported previously. In the paramagnetic phase of Fe2SiO4, at temperatures of 70 K and above, we find that the temperature dependence of the linear thermal expansion coefficient of the b axis takes an unusual form. In contrast to the behaviour of the expansion coefficients of the unit-cell volume and of the a and c axes, which show the expected reduction in magnitude below ~300 K, that of the b axis remains almost constant between ~70 K and 1000 K.