8,776 results on '"Price, Cj"'
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2. Dissociating Cerebellar Regions Involved in Formulating and Articulating Words and Sentences.
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Parker Jones O, Geva S, Prejawa S, Hope TMH, Oberhuber M, Seghier ML, Green DW, and Price CJ
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We investigated which parts of the cerebellum are involved in formulating and articulating sentences using (i) a sentence production task that involved describing simple events in pictures; (ii) an auditory sentence repetition task involving the same sentence articulation but not sentence formulation; and (iii) an auditory sentence-to-picture matching task that involved the same pictorial events and no overt articulation. Activation for each of these tasks was compared to the equivalent word processing tasks: noun production, verb production, auditory noun repetition, and auditory noun-to-picture matching. We associate activation in bilateral cerebellum lobule VIIb with sequencing words into sentences because it increased for sentence production compared to all other conditions and was also activated by word production compared to word matching. We associate a paravermal part of right cerebellar lobule VIIIb with overt motor execution of speech, because activation was higher during (i) production and repetition of sentences compared to the corresponding noun conditions and (ii) noun and verb production compared to all matching tasks, with no activation relative to fixation during any silent (nonspeaking) matching task. We associate activation within right cerebellar Crus II with covert articulatory activity because it activated for (i) all speech production more than matching tasks and (ii) sentences compared to nouns during silent (nonspeaking) matching as well as sentence production and sentence repetition. Our study serendipitously segregated, for the first time, three distinct functional roles for the cerebellum in generic speech production, and it demonstrated how sentence production enhanced the demands on these cerebellar regions., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)
- Published
- 2024
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3. Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.
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Stavish D, Price CJ, Gelezauskaite G, Alsehli H, Leonhard KA, Taapken SM, McIntire EM, Laing O, James BM, Riley JJ, Zerbib J, Baker D, Harding AL, Jestice LH, Eleveld TF, Gillis AJM, Hillenius S, Looijenga LHJ, Gokhale PJ, Ben-David U, Ludwig TE, and Barbaric I
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- Humans, Cell Cycle Proteins metabolism, Cell Cycle Proteins genetics, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins genetics, Cell Culture Techniques methods, Apoptosis genetics, Feeder Cells cytology, Cell Line, Cells, Cultured, Chromosomes, Human, Pair 1 genetics, Pluripotent Stem Cells metabolism, Pluripotent Stem Cells cytology
- Abstract
Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection., Competing Interests: Declaration of interests T.E.L. is a co-inventor and receives a share of royalties on various hPSC media- and culture-related patents currently owned and licensed by the Wisconsin Alumni Research Foundation (WARF). I.B. is a member of the scientific advisory board of WiCell. U.B.-D. received consulting fees from Accent Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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4. Mental Health Distress Is Associated With Higher Pain Interference in Patients With Opioid Use Disorder Stabilized on Buprenorphine or Methadone.
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Leyde S, Price CJ, Colgan DD, Pike KC, Tsui JI, and Merrill JO
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- Humans, Male, Female, Adult, Middle Aged, Depression epidemiology, Depression drug therapy, Depression psychology, Stress Disorders, Post-Traumatic epidemiology, Stress Disorders, Post-Traumatic psychology, Stress Disorders, Post-Traumatic drug therapy, Buprenorphine therapeutic use, Opioid-Related Disorders psychology, Opioid-Related Disorders epidemiology, Opioid-Related Disorders drug therapy, Methadone therapeutic use, Chronic Pain drug therapy, Chronic Pain psychology, Chronic Pain epidemiology, Opiate Substitution Treatment, Analgesics, Opioid therapeutic use, Anxiety epidemiology, Anxiety drug therapy, Anxiety psychology
- Abstract
Background: The relationships between opioid use disorder (OUD), chronic pain, and mental health distress are complex and multidirectional. The objective of this exploratory study was to examine the relationship between mental health conditions and Chronic pain severity and interference among patients stabilized on either buprenorphine or methadone., Methods: We report baseline data from a randomized trial of a mind-body intervention conducted at 5 outpatient clinics that provided either buprenorphine or methadone treatment. Validated scales were used to measure substance use, mental health distress, and pain severity and interference. Statistical analyses examined the relationship between mental health conditions and pain severity and interference., Results: Of 303 participants, 57% (n = 172) reported Chronic pain. A total of 88% (n = 268) were prescribed buprenorphine. Mental health conditions were common, with one-quarter of the sample screening positive for all 3 mental health conditions (anxiety, depression, and posttraumatic stress disorder [PTSD]). Compared to participants without Chronic pain, participants with Chronic pain were more likely to screen positive for moderate-severe anxiety (47% vs 31%); moderate-severe depression (54% vs 41%); and the combination of anxiety, depression, and PTSD (31% vs 18%). Among participants with Chronic pain, mental health conditions were associated with higher pain interference. Pain severity was higher among participants with mental health conditions, but only reached statistical significance for depression. Pain interference scores increased with a higher number of co-occurring mental health conditions., Conclusions: Among individuals stabilized on either buprenorphine or methadone, highly symptomatic and comorbid mental health distress is common and is associated with increased pain interference. Adequate screening for, and treatment of, mental health conditions in patients with OUD and Chronic pain is needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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5. Leveraging AI to improve evidence synthesis in conservation.
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Berger-Tal O, Wong BBM, Adams CA, Blumstein DT, Candolin U, Gibson MJ, Greggor AL, Lagisz M, Macura B, Price CJ, Putman BJ, Snijders L, and Nakagawa S
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- Conservation of Natural Resources methods, Artificial Intelligence, Biodiversity
- Abstract
Systematic evidence syntheses (systematic reviews and maps) summarize knowledge and are used to support decisions and policies in a variety of applied fields, from medicine and public health to biodiversity conservation. However, conducting these exercises in conservation is often expensive and slow, which can impede their use and hamper progress in addressing the current biodiversity crisis. With the explosive growth of large language models (LLMs) and other forms of artificial intelligence (AI), we discuss here the promise and perils associated with their use. We conclude that, when judiciously used, AI has the potential to speed up and hopefully improve the process of evidence synthesis, which can be particularly useful for underfunded applied fields, such as conservation science., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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6. Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: differences by gender, PTSD status, and chronic pain.
- Author
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Rodríguez MN, Colgan DD, Leyde S, Pike K, Merrill JO, and Price CJ
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- Humans, Female, Male, Cross-Sectional Studies, Adult, Sex Factors, Middle Aged, Psychological Trauma epidemiology, Stress Disorders, Post-Traumatic epidemiology, Stress Disorders, Post-Traumatic drug therapy, Chronic Pain drug therapy, Chronic Pain epidemiology, Opioid-Related Disorders drug therapy, Opioid-Related Disorders epidemiology
- Abstract
Background: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain., Methods: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression., Results: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%)., Conclusion: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment., Trial Registration: NCT04082637., (© 2024. The Author(s).)
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- 2024
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7. Body Awareness: A phenomenological inquiry into the common ground of mind-body therapies
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Mehling, WE, Wrubel, J, Daubenmier, JJ, Price, CJ, Kerr, CE, Silow, T, Gopisetty, V, and Stewart, AL
- Abstract
Enhancing body awareness has been described as a key element or a mechanism of action for therapeutic approaches often categorized as mind-body approaches, such as yoga, TaiChi, Body-Oriented Psychotherapy, Body Awareness Therapy, mindfulness based therapies/meditation, Feldenkrais, Alexander Method, Breath Therapy and others with reported benefits for a variety of health conditions. To better understand the conceptualization of body awareness in mind-body therapies, leading practitioners and teaching faculty of these approaches were invited as well as their patients to participate in focus groups. The qualitative analysis of these focus groups with representative practitioners of body awareness practices, and the perspectives of their patients, elucidated the common ground of their understanding of body awareness. For them body awareness is an inseparable aspect of embodied self awareness realized in action and interaction with the environment and world. It is the awareness of embodiment as an innate tendency of our organism for emergent self-organization and wholeness. The process that patients undergo in these therapies was seen as a progression towards greater unity between body and self, very similar to the conceptualization of embodiment as dialectic of body and self described by some philosophers as being experienced in distinct developmental levels. © 2011 Mehling et al; licensee BioMed Central Ltd.
- Published
- 2011
8. Olfactory misinformation provides refuge to palatable plants from mammalian browsing.
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Finnerty PB, Possell M, Banks PB, Orlando CG, Price CJ, Shrader AM, and McArthur C
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- Animals, Seedlings, Trees, Mammals, Herbivory, Plants, Odorants
- Abstract
Mammalian herbivores browse palatable plants of ecological and economical value. Undesirable neighbours can reduce browsing to these plants by providing 'associational refuge', but they can also compete for resources. Here we recreated the informative odour emitted by undesirable plants. We then tested whether this odour could act as virtual neighbours, providing browsing refuge to palatable eucalyptus tree seedlings. We found that protection using this method was equivalent to protection provided by real plants. Palatable seedlings were 17-20 times more likely to be eaten by herbivores without virtual, or real, neighbours. Because many herbivores use plant odour to forage, virtual neighbours could provide a useful practical management approach to help protect valued plants., (© 2024. The Author(s).)
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- 2024
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9. Modeling the selective growth advantage of genetically variant human pluripotent stem cells to identify opportunities for manufacturing process control.
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Beltran-Rendon C, Price CJ, Glen K, Stacey A, Barbaric I, and Thomas RJ
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- Humans, Cell Differentiation genetics, Coculture Techniques, Cell Culture Techniques, Pluripotent Stem Cells
- Abstract
Background Aims: The appearance of genetically variant populations in human pluripotent stem cell (hPSC) cultures represents a concern for research and clinical applications. Genetic variations may alter hPSC differentiation potential or cause phenotype variation in differentiated cells. Further, variants may have properties such as proliferative rate, or response to the culture environment, that differ from wild-type cells. As such, understanding the behavior of these variants in culture, and any potential operational impact on manufacturing processes, will be necessary to control quality of putative hPSC-based products that include a proportion of variant threshold in their quality specification., Methods: Here we show a computational model that mathematically describes the growth dynamics between commonly occurring genetically variant hPSCs and their counterpart wild-type cells in culture., Results: We show that our model is capable of representing the growth behaviors of both wild-type and variant hPSCs in individual and co-culture systems., Conclusions: This representation allows us to identify three critical process parameters that drive critical quality attributes when genetically variant cells are present within the system: total culture density, proportion of variant cells within the culture system and variant cell overgrowth. Lastly, we used our model to predict how the variability of these parameters affects the prevalence of both populations in culture., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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10. Predicting Online Behavioural Responses to Transcranial Direct Current Stimulation in Stroke Patients with Anomia.
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Hope TMH, Ondobaka S, Akkad H, Nardo D, Pappa K, Price CJ, Leff AP, and Crinion JT
- Abstract
Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks' performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it.
- Published
- 2024
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11. Principal component analysis-based latent-space dimensionality under-estimation, with uncorrelated latent variables.
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Hope TMH, Halai A, Crinion J, Castelli P, Price CJ, and Bowman H
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- Humans, Principal Component Analysis, Algorithms
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- 2024
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12. Testing the disconnectome symptom discoverer model on out-of-sample post-stroke language outcomes.
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Hope TMH, Neville D, Talozzi L, Foulon C, Forkel SJ, de Schotten MT, and Price CJ
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- Humans, Language, Stroke complications
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- 2024
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13. Linguistical choice in Tasmanian environmental discourse : a study of the prevalence and impact of military terminology in the upper Florentine Valley forestry dispute, 2008-2012
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Price, CJ
- Abstract
The project examines the ubiquity and impact of military discourse in the context of disputation over the fate of natural areas. Though typically tense, anger-inducing and confrontational, do such face-offs merit the label 'war'? It is argued here that they do not; that there are defining features of 'war' that do not apply to its metaphoric deployment in environmental conflict. The nature of metaphor and its discursive purpose and standing are first examined, followed by a consideration of the readiness with which warfare metaphors tend to be applied to a range of non-military situations. Environmental discourse is particularly saturated with metaphors borrowed from warfare. The project takes, as a case study, the dramatic on-site confrontation between (mostly) young forest activists and logging contractors and police in the upper Florentine Valley in the Tasmanian south-west. Protesters set up a permanent camp ‚Äö- 'Camp Florentine' ‚Äö- on the proposed line of access to the gazetted forest coupes, remaining determinedly in occupation for several years until logging operations were, for the time being, halted. Using semi-structured interviews a number of principal actors in the dispute were interviewed. Most, but not all, agreed that the use of military terminology in relation to the dispute was inappropriate. On the question of the impact of the widespread use of warfare-derived metaphors on the psychology and consequent comportment of participants in contestation over environmental goods ‚Äö- in this case, wild forest ecosystems ‚Äö- there was even less consensus.
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- 2023
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14. Properties of Layered TMDC Superlattices for Electrodes in Li-Ion and Mg-Ion Batteries.
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Price CJ, Baker EAD, and Hepplestone SP
- Abstract
In this work, we present a first-principles investigation of the properties of superlattices made from transition metal dichalcogenides for use as electrodes in lithium-ion and magnesium-ion batteries. From a study of 50 pairings, we show that, in general, the volumetric expansion, intercalation voltages, and thermodynamic stability of vdW superlattice structures can be well approximated with the average value of the equivalent property for the component layers. We also found that the band gap can be reduced, improving the conductivity. Thus, we conclude that superlattice construction can be used to improve material properties through the tuning of intercalation voltages toward specific values and by increasing the stability of conversion-susceptible materials. For example, we demonstrate how pairing SnS
2 with systems such as MoS2 can change it from a conversion to an intercalation material, thus opening it up for use in intercalation electrodes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)- Published
- 2024
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15. Hyperspectral Mapping of Human Primary and Stem Cells at Cell-Matrix Interfaces.
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De Santis E, Faruqui N, Russell CT, Noble JE, Kepiro IE, Hammond K, Tsalenchuk M, Ryadnov EM, Wolna M, Frogley MD, Price CJ, Barbaric I, Cinque G, and Ryadnov MG
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- Humans, Tissue Engineering methods, Extracellular Matrix chemistry, Embryonic Stem Cells, Tissue Scaffolds chemistry, Biocompatible Materials chemistry
- Abstract
Extracellular matrices interface with cells to promote cell growth and tissue development. Given this critical role, matrix mimetics are introduced to enable biomedical materials ranging from tissue engineering scaffolds and tumor models to organoids for drug screening and implant surface coatings. Traditional microscopy methods are used to evaluate such materials in their ability to support exploitable cell responses, which are expressed in changes in cell proliferation rates and morphology. However, the physical imaging methods do not capture the chemistry of cells at cell-matrix interfaces. Herein, we report hyperspectral imaging to map the chemistry of human primary and embryonic stem cells grown on matrix materials, both native and artificial. We provide the statistical analysis of changes in lipid and protein content of the cells obtained from infrared spectral maps to conclude matrix morphologies as a major determinant of biochemical cell responses. The study demonstrates an effective methodology for evaluating bespoke matrix materials directly at cell-matrix interfaces.
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- 2024
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16. Computational Study of the Enhancement of Graphene Electrodes for Use in Li-Ion Batteries via Forming Superlattices with Transition Metal Dichalcogenides.
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Baker EAD, Price CJ, and Hepplestone SP
- Abstract
In our study, we examined nine transition metal dichalcogenide (TMDC)-graphene superlattices as potential Li-ion intercalation electrodes. We determined their voltages, with ScS
2 -graphene in T- and R-phases showing the highest at around 3 V, while the others ranged from 0 to 1.5 V. Most superlattices exhibited minimal volumetric expansion (5 to 10%), similar to NMC (8%), except for SnS2 -T and NiS2 -T, which expanded up to nearly 20%. We evaluated their capacities using a stability metric, EIS , and found that ScS2 -T, ScS2 -R, and TiS2 -T could be intercalated up to two Li ions per MX2 unit without decomposing to Li2 S, yielding capacities of 306.77 mA h/g for both ScS2 phases and 310.84 mA h/g for TiS2 -T, roughly equivalent to LiC2 . MoS2 -T could accept Li up to a limit of a = 15/16 in Lia MoS2 Cb , corresponding to a capacity of 121.29 mA h/g (equivalent to LiC4 ). Examining the influence of graphene layers on MoS2 -T, we observed a voltage decrease and an initial EIS decrease before effectively flat lining, which is due to charge donation to the middle graphene layer, reducing the electron concentration near the TMDC layer. As graphene layers increased, overall volume expansion decreased with Li intercalation, which is attributed to the in-plane expansion changing. Our results underscore the potential of TMDC-graphene superlattices as Li-ion intercalation electrodes, offering low volumetric expansions, high capacities, and a wide voltage range. These superlattices all show an increase in the capacity of the graphene., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)- Published
- 2024
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17. Predicting recovery following stroke: Deep learning, multimodal data and feature selection using explainable AI.
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White A, Saranti M, d'Avila Garcez A, Hope TMH, Price CJ, and Bowman H
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- Humans, Female, Male, Aged, Middle Aged, Recovery of Function physiology, Stroke Rehabilitation methods, Neural Networks, Computer, Adult, Neuroimaging methods, Aged, 80 and over, Deep Learning, Stroke diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Machine learning offers great potential for automated prediction of post-stroke symptoms and their response to rehabilitation. Major challenges for this endeavour include the very high dimensionality of neuroimaging data, the relatively small size of the datasets available for learning and interpreting the predictive features, as well as, how to effectively combine neuroimaging and tabular data (e.g. demographic information and clinical characteristics). This paper evaluates several solutions based on two strategies. The first is to use 2D images that summarise MRI scans. The second is to select key features that improve classification accuracy. Additionally, we introduce the novel approach of training a convolutional neural network (CNN) on images that combine regions-of-interests (ROIs) extracted from MRIs, with symbolic representations of tabular data. We evaluate a series of CNN architectures (both 2D and a 3D) that are trained on different representations of MRI and tabular data, to predict whether a composite measure of post-stroke spoken picture description ability is in the aphasic or non-aphasic range. MRI and tabular data were acquired from 758 English speaking stroke survivors who participated in the PLORAS study. Each participant was assigned to one of five different groups that were matched for initial severity of symptoms, recovery time, left lesion size and the months or years post-stroke that spoken description scores were collected. Training and validation were carried out on the first four groups. The fifth (lock-box/test set) group was used to test how well model accuracy generalises to new (unseen) data. The classification accuracy for a baseline logistic regression was 0.678 based on lesion size alone, rising to 0.757 and 0.813 when initial symptom severity and recovery time were successively added. The highest classification accuracy (0.854), area under the curve (0.899) and F1 score (0.901) were observed when 8 regions of interest were extracted from each MRI scan and combined with lesion size, initial severity and recovery time in a 2D Residual Neural Network (ResNet). This was also the best model when data were limited to the 286 participants with moderate or severe initial aphasia (with area under curve = 0.865), a group that would be considered more difficult to classify. Our findings demonstrate how imaging and tabular data can be combined to achieve high post-stroke classification accuracy, even when the dataset is small in machine learning terms. We conclude by proposing how the current models could be improved to achieve even higher levels of accuracy using images from hospital scanners., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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18. Trauma Exposure Across the Lifespan among Individuals Engaged in Treatment with Medication for Opioid Use Disorder: Differences by Gender, PTSD Status, and Chronic Pain.
- Author
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Rodríguez MN, Colgan DD, Leyde S, Pike K, Merrill JO, and Price CJ
- Abstract
Background: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain., Methods: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression., Results: Participants were self-identified as women ( n = 157), men ( n = 144), and non-binary ( n = 2). Fifty-seven percent ( n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%)., Conclusions: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment., Trial Registration: NCT04082637., Competing Interests: Competing interests: The authors declare that they have no competing interests.
- Published
- 2023
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19. Degeneracy in the neurological model of auditory speech repetition.
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Sajid N, Gajardo-Vidal A, Ekert JO, Lorca-Puls DL, Hope TMH, Green DW, Friston KJ, and Price CJ
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- Humans, Brain diagnostic imaging, Brain physiology, Brain Mapping, Models, Neurological, Speech physiology, Motor Cortex diagnostic imaging, Motor Cortex physiology
- Abstract
Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage., (© 2023. The Author(s).)
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- 2023
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20. Within-Person Modulation of Neural Networks following Interoceptive Awareness Training through Mindful Awareness in Body-Oriented Therapy (MABT): A Pilot Study.
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Price CJ, Sevinc G, and Farb NAS
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Interoception, the representation of the body's internal state, is increasingly recognized for informing subjective wellbeing and promoting regulatory behavior. However, few empirical reports characterize interoceptive neural networks, and fewer demonstrate changes to these networks in response to an efficacious intervention. Using a two-group randomized controlled trial, this pilot study explored within-participant neural plasticity in interoceptive networks following Mindful Awareness in Body-oriented Therapy (MABT). Participants (N = 22) were assigned to either 8 weeks of MABT or to a no-treatment control and completed baseline and post-intervention assessments that included subjective interoceptive awareness (MAIA) and neuroimaging of an interoceptive awareness task. MABT was uniquely associated with insula deactivation, increased functional connectivity between the dorsal attention network and the somatomotor cortex, and connectivity changes correlated positively with changes in subjective interoception. Within the MABT group, changes in subjective interoception interacted with changes in a predefined anterior cingulate seed region to predict changes in right middle insula activity, a putative primary interoceptive representation region. While the small sample size requires the replication of findings, results suggest that interoceptive training enhances sensory-prefrontal connectivity, and that such changes are commensurate with enhanced interoceptive awareness.
- Published
- 2023
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21. The ethics of intervening in animal behaviour for conservation.
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van Dooren T, Price CJ, Banks PB, Berger-Tal O, Chrulew M, Johnson J, Lajeunesse G, Lynch KE, McArthur C, Parker FCG, Oakey M, Pitcher BJ, St Clair CC, Ward-Fear G, Widin S, Wong BBM, and Blumstein DT
- Subjects
- Animals, Humans, Behavior, Animal, Research Personnel, Conservation of Natural Resources, Animals, Wild
- Abstract
Conservation behaviour is a growing field that applies insights from the study of animal behaviour to address challenges in wildlife conservation and management. Conservation behaviour interventions often aim to manage specific behaviours of a species to solve conservation challenges. The field is often viewed as offering approaches that are less intrusive or harmful to animals than, for example, managing the impact of a problematic species by reducing its population size (frequently through lethal control). However, intervening in animal behaviour, even for conservation purposes, may still raise important ethical considerations. We discuss these issues and develop a framework and a decision support tool, to aid managers and researchers in evaluating the ethical considerations of conservation behaviour interventions against other options., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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22. Properties of Packed Bed Structures Formed during Filtration: A Two and Three-Dimensional Model.
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Eales W, Price CJ, Hicks W, and Mulheran PA
- Abstract
Agglomeration is an issue that causes many problems during secondary processing for pharmaceutical companies, causing material to need further processing and costing additional time and resources to ensure a satisfactory outcome. A potential source of agglomeration arises from the particle contacts established during filtration that lead to robust agglomerates forming during drying, so that a necessary first step toward understanding agglomeration is to study the packing properties of filtration beds. Here, we present two and three-dimensional models simulating the formation of packed bed structures during filtration. The models use circular and spherical particles of different sizes, mimicking the bimodal particle size distributions sometimes encountered in industrial practice. The statistics of packing and void formation, along with the distribution of interparticle contacts and percolation structures, are presented and discussed in the context of filtration, drying, and agglomeration. The model paves the way for predictive capabilities that can lead to the rational design of processes to minimize the impact of agglomeration., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)
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- 2023
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23. Self-reported interoceptive awareness in primary care patients with past or current low back pain
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Mehling WE, Daubenmier J, Price CJ, Acree M, Bartmess E, and Stewart AL
- Subjects
Medicine (General) ,R5-920 - Abstract
Wolf E Mehling,1,2 Jennifer Daubenmier,1,3 Cynthia J Price,5 Mike Acree,1 Elizabeth Bartmess,1 Anita L Stewart41Osher Center for Integrative Medicine, 2Department of Family and Community Medicine, 3Department of Medicine, 4School of Nursing, Institute for Health and Aging, University of California, San Francisco, CA, 5School of Nursing, Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USABackground: Mind–body interactions play a major role in the prognosis of chronic pain, and mind–body therapies such as meditation, yoga, Tai Chi, and Feldenkrais presumably provide benefits for pain patients. The Multidimensional Assessment of Interoceptive Awareness (MAIA) scales, designed to measure key aspects of mind–body interaction, were developed and validated with individuals practicing mind–body therapies, but have never been used in pain patients.Methods: We administered the MAIA to primary care patients with past or current low back pain and explored differences in the performance of the MAIA scales between this and the original validation sample. We compared scale means, exploratory item cluster and confirmatory factor analyses, scale–scale correlations, and internal-consistency reliability between the two samples and explored correlations with validity measures.Results: Responses were analyzed from 435 patients, of whom 40% reported current pain. Cross-sectional comparison between the two groups showed marked differences in eight aspects of interoceptive awareness. Factor and cluster analyses generally confirmed the conceptual model with its eight dimensions in a pain population. Correlations with validity measures were in the expected direction. Internal-consistency reliability was good for six of eight MAIA scales. We provided specific suggestions for their further development.Conclusion: Self-reported aspects of interoceptive awareness differ between primary care patients with past or current low back pain and mind–body trained individuals, suggesting further research is warranted on the question whether mind–body therapies can alter interoceptive attentional styles with pain. The MAIA may be useful in assessing changes in aspects of interoceptive awareness and in exploring the mechanism of action in trials of mind–body interventions in pain patients.Keywords: interoception, body awareness, low back pain, questionnaire
- Published
- 2013
24. A machine learning approach towards the differentiation between interoceptive and exteroceptive attention.
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Zuo ZX, Price CJ, and Farb NAS
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- Humans, Reproducibility of Results, Attention, Emotions, Heart Rate, Awareness, Interoception
- Abstract
Interoception, the representation of the body's internal state, plays a central role in emotion, motivation and wellbeing. Interoceptive sensibility, the ability to engage in sustained interoceptive awareness, is particularly relevant for mental health but is exclusively measured via self-report, without methods for objective measurement. We used machine learning to classify interoceptive sensibility by contrasting using data from a randomized control trial of interoceptive training, with functional magnetic resonance imaging assessment before and after an 8-week intervention (N = 44 scans). The neuroimaging paradigm manipulated attention targets (breath vs. visual stimuli) and reporting demands (active reporting vs. passive monitoring). Machine learning achieved high accuracy in distinguishing between interoceptive and exteroceptive attention, both for within-session classification (~80% accuracy) and out-of-sample classification (~70% accuracy), revealing the reliability of the predictions. We then explored the classifier potential for 'reading out' mental states in a 3-min sustained interoceptive attention task. Participants were classified as actively engaged about half of the time, during which interoceptive training enhanced their ability to sustain interoceptive attention. These findings demonstrate that interoceptive and exteroceptive attention is distinguishable at the neural level; these classifiers may help to demarcate periods of interoceptive focus, with implications for developing an objective marker for interoceptive sensibility in mental health research., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
- Published
- 2023
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25. Interoceptive Awareness of the Breath Preserves Attention and Language Networks amidst Widespread Cortical Deactivation: A Within-Participant Neuroimaging Study.
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Farb NAS, Zuo Z, and Price CJ
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- Humans, Brain Mapping, Emotions physiology, Neuroimaging, Heart Rate physiology, Awareness physiology, Magnetic Resonance Imaging
- Abstract
Interoception, the representation of the body's internal state, serves as a foundation for emotion, motivation, and wellbeing. Yet despite its centrality in human experience, the neural mechanisms of interoceptive attention are poorly understood. The Interoceptive/Exteroceptive Attention Task (IEAT) is a novel neuroimaging paradigm that compares behavioral tracking of the respiratory cycle (Active Interoception) to tracking of a visual stimulus (Active Exteroception). Twenty-two healthy participants completed the IEAT during two separate scanning sessions ( N = 44) as part of a randomized control trial of mindful awareness in body-oriented therapy (MABT). Compared with Active Exteroception, Active Interoception deactivated somatomotor and prefrontal regions. Greater self-reported interoceptive sensibility (MAIA scale) predicted sparing from deactivation within the anterior cingulate cortex (ACC) and left-lateralized language regions. The right insula, typically described as a primary interoceptive cortex, was only specifically implicated by its deactivation during an exogenously paced respiration condition (Active Matching) relative to self-paced Active Interoception. Psychophysiological interaction (PPI) analysis characterized Active Interoception as promoting greater ACC connectivity with lateral prefrontal and parietal regions commonly referred to as the dorsal attention network (DAN). In contrast to evidence relating accurate detection of liminal interoceptive signals such as the heartbeat to anterior insula activity, interoceptive attention toward salient signals such as the respiratory cycle may involve reduced cortical activity but greater ACC-DAN connectivity, with greater sensibility linked to reduced deactivation within the ACC and language-processing regions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Farb et al.)
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- 2023
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26. Interpreting and validating complexity and causality in lesion-symptom prognoses.
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Seghier ML and Price CJ
- Abstract
This paper considers the steps needed to generate pragmatic and interpretable lesion-symptom mappings that can be used for clinically reliable prognoses. The novel contributions are 3-fold. We first define and inter-relate five neurobiological and five methodological constraints that need to be accounted for when interpreting lesion-symptom associations and generating synthetic lesion data. The first implication is that, because of these constraints, lesion-symptom mapping needs to focus on probabilistic relationships between Lesion and Symptom, with Lesion as a multivariate spatial pattern, Symptom as a time-dependent behavioural profile and evidence that Lesion raises the probability of Symptom. The second implication is that in order to assess the strength of probabilistic causality, we need to distinguish between causal lesion sites, incidental lesion sites, spared but dysfunctional sites and intact sites, all of which might affect the accuracy of the predictions and prognoses generated. We then formulate lesion-symptom mappings in logical notations, including combinatorial rules, that are then used to evaluate and better understand complex brain-behaviour relationships. The logical and theoretical framework presented applies to any type of neurological disorder but is primarily discussed in relationship to stroke damage. Accommodating the identified constraints, we discuss how the 1965 Bradford Hill criteria for inferring probabilistic causality, post hoc , from observed correlations in epidemiology-can be applied to lesion-symptom mapping in stroke survivors. Finally, we propose that rather than rely on post hoc evaluation of how well the causality criteria have been met, the neurobiological and methodological constraints should be addressed, a priori , by changing the experimental design of lesion-symptom mappings and setting up an open platform to share and validate the discovery of reliable and accurate lesion rules that are clinically useful., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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27. Enhanced left superior parietal activation during successful speech production in patients with left dorsal striatal damage and error-prone neurotypical participants.
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Geva S, Schneider LM, Khan S, Lorca-Puls DL, Gajardo-Vidal A, Hope TMH, Green DW, and Price CJ
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- Adult, Humans, Magnetic Resonance Imaging, Parietal Lobe, Putamen, Speech physiology, Stroke complications, Stroke diagnostic imaging, Stroke pathology
- Abstract
Functional imaging studies of neurotypical adults report activation in the left putamen during speech production. The current study asked how stroke survivors with left putamen damage are able to produce correct spoken responses during a range of speech production tasks. Using functional magnetic resonance imaging, activation during correct speech production responses was assessed in 5 stroke patients with circumscribed left dorsal striatal lesions, 66 stroke patient controls who did not have focal left dorsal striatal lesions, and 54 neurotypical adults. As a group, patients with left dorsal striatal damage (our patients of interest) showed higher activation than neurotypical controls in the left superior parietal cortex during successful speech production. This effect was not specific to patients with left dorsal striatal lesions as we observed enhanced activation in the same region in some patient controls and also in more error-prone neurotypical participants. Our results strongly suggest that enhanced left superior parietal activation supports speech production in diverse challenging circumstances, including those caused by stroke damage. They add to a growing body of literature indicating how upregulation within undamaged parts of the neural systems already recruited by neurotypical adults contributes to recovery after stroke., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2023
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28. A guide to group effective connectivity analysis, part 2: Second level analysis with PEB
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Zeidman, P, Jafarian, A, Seghier, ML, Litvak, V, Cagnan, H, Price, CJ, and Friston, KJ
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Adult ,Connectome ,Humans ,Prefrontal Cortex ,Guidelines as Topic ,Models, Theoretical ,Nerve Net ,Magnetic Resonance Imaging ,Article - Abstract
This paper provides a worked example of using Dynamic Causal Modelling (DCM) and Parametric Empirical Bayes (PEB) to characterise inter-subject variability in neural circuitry (effective connectivity). It steps through an analysis in detail and provides a tutorial style explanation of the underlying theory and assumptions (i.e, priors). The analysis procedure involves specifying a hierarchical model with two or more levels. At the first level, state space models (DCMs) are used to infer the effective connectivity that best explains a subject's neuroimaging timeseries (e.g. fMRI, MEG, EEG). Subject-specific connectivity parameters are then taken to the group level, where they are modelled using a General Linear Model (GLM) that partitions between-subject variability into designed effects and additive random effects. The ensuing (Bayesian) hierarchical model conveys both the estimated connection strengths and their uncertainty (i.e., posterior covariance) from the subject to the group level; enabling hypotheses to be tested about the commonalities and differences across subjects. This approach can also finesse parameter estimation at the subject level, by using the group-level parameters as empirical priors. The preliminary first level (subject specific) DCM for fMRI analysis is covered in a companion paper. Here, we detail group-level analysis procedures that are suitable for use with data from any neuroimaging modality. This paper is accompanied by an example dataset, together with step-by-step instructions demonstrating how to reproduce the analyses., Highlights • This guide walks through a group effective connectivity study using DCM and PEB. • It explains recently developed tools for hierarchical Bayesian modelling. • The appendices clarify the technical detail of the PEB framework and its priors. • An accompanying dataset is provided with step-by-step analysis instructions.
- Published
- 2020
29. First principles study of layered scandium disulfide for use as Li-ion and beyond-Li-ion batteries.
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Price CJ, Pitfield J, Baker EAD, and Hepplestone SP
- Abstract
The growing demand for high efficiency portable batteries has prompted a deeper exploration for alternative cathode materials. Due to low Earth abundance, scandium has not received much attention, however its low atomic mass makes it ideal for high gravimetric capacity electrodes. Here we have performed a comprehensive first-principles study to assess the performance of layered ScS
2 as a potential cathode for lithium-ion and beyond-lithium-ion batteries. We have explored the configuration space of ScS2 and its intercalated compounds using a mix of machine learning and ab initio techniques, finding the ground state geometry to be layered in nature. This layered structure is found to have a high voltage, reaching above 4.5 V for Group I intercalants, ideal volume expansions below 10% for lithium and magnesium intercalation, is electronically conductive, and is ductile once intercalated. Of the intercalants considered, we find that lithium is the best choice for cathode applications, for which we have used a combination of thermodynamic phase diagrams, ab intio phonon calculations, and evaluation of the elastic tensor to conclude that ScS2 possesses a reversible capacity of 182.99 mA h g-1 , on par with current state of the art cathode materials such as LiCoO2 , NMC, and NCA. Finally, we substitute foreign metal species into the ScS2 material to determine their effect on key cathode properties, but find that these are overall detrimental to the performance of ScS2 . This does, however, highlight the potential for improvement if scandium were mixed into other layered systems such as the layered transition metal oxides.- Published
- 2023
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30. Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling.
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Ottoboni S, Brown CJ, Mehta B, Jimeno G, Mitchell NA, Sefcik J, and Price CJ
- Abstract
To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work reported here combines filtration and washing operations used in active pharmaceutical ingredient (API) purification and isolation to predict isolation performance without the need of extensive experimental work. A fixed Carman-Kozeny filtration model is integrated with several washing mechanisms (displacement, dilution, and axial dispersion). Two limiting cases are considered: case 1 where there is no change in the solid phase during isolation (no particle dissolution and/or growth), and case 2 where the liquid and solid phases are equilibrated over the course of isolation. In reality, all actual manufacturing conditions would be bracketed by these two limiting cases, so consideration of these two scenarios provides rigorous theoretical bounds for assessing isolation performance. This modeling approach aims to facilitate the selection of most appropriate models suitable for different isolation scenarios, without the requirement to use overly complex models for straightforward isolation processes. Mefenamic acid and paracetamol were selected as representative model compounds to assess a range of isolation scenarios. In each case, the objective of the models was to identify the purity of the product reached with a fixed wash ratio and minimize the changes to the crystalline particle attributes that occur during the isolation process. This was undertaken with the aim of identifying suitable criteria for the selection of appropriate filtration and washing models corresponding to relevant processing conditions, and ultimately developing guidelines for the digital design of filtration and washing processes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)
- Published
- 2022
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31. Better long-term speech outcomes in stroke survivors who received early clinical speech and language therapy: What's driving recovery?
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Roberts S, Bruce RM, Lim L, Woodgate H, Ledingham K, Anderson S, Lorca-Puls DL, Gajardo-Vidal A, Leff AP, Hope TMH, Green DW, Crinion JT, and Price CJ
- Subjects
- Humans, Language Therapy, Speech, Speech Therapy, Survivors, Aphasia etiology, Stroke complications, Stroke therapy
- Abstract
Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical therapy in the first month post-stroke. In contrast to prior studies, we factored out variance from: initial severity of speaking impairment, amount of later therapy, and left and right hemisphere lesion size and site. We found that speaking ability at one month post-stroke was significantly better in patients who received early therapy ( n = 79), versus those who did not ( n = 64), and the number of hours of early therapy was positively related to recovery at one year post-stroke. We offer two non-mutually exclusive interpretations of these data: (1) patients may benefit from the early provision of self-management strategies; (2) therapy is more likely to be provided to patients who have a better chance of recovery (e.g., poor physical and/or mental health may impact suitability for therapy and chance of recovery). Both interpretations have implications for future studies aiming to predict individual patients' speech outcomes after stroke, and their response to therapy.
- Published
- 2022
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32. A mechanistic understanding of prebaiting to improve interaction with wildlife management devices.
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Bytheway JP, Johnstone KC, Price CJ, and Banks PB
- Subjects
- Animals, Rats, Animals, Wild
- Abstract
Background: Prebaiting is a technique involving early deployment of 'unarmed' devices (e.g. baits and traps) to increase efficacy of wildlife management. Although commonly used, the mechanisms by which prebaiting works are poorly understood. We propose three mechanisms by which prebaiting may increase device interaction probabilities; (1) overcoming neophobia towards novel devices, (2) a 'trickle in' effect increasing time for animals to encounter devices; and (3) social information transfer about rewards associated with devices. We conducted a survey of 100 articles to understand how prebaiting has been used. We then tested our proposed prebaiting mechanisms using a global pest (black rats, Rattus rattus) examining how uniquely marked free-living rats responded to a common yet novel monitoring technique (tracking tunnels)., Results: No studies in our dataset tested how prebaiting functioned. Most studies (61%) did not propose a mechanism for prebaiting, but overcoming neophobia was most commonly mentioned. We only found partial support for the overcoming neophobia hypothesis in our field test. We found the dominant mechanism operating in our system to be the 'trickle in' effect with the proportion of individuals visiting the device increasing over time. We found no support for social information transfer as a mechanism of prebaiting., Conclusion: Applying a mechanistic understanding of how prebaiting functions will improve the efficacy of management devices. Our results suggest that prebaiting allows time for more rats to encounter a device, hence surveys in our system would benefit from long prebaiting periods. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)
- Published
- 2021
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33. Less is more: neural mechanisms underlying anomia treatment in chronic aphasic patients
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Nardo, D., Holland, R., Leff, AP, Price, CJ, Crinion, JT, Nardo, Davide, Holland, Rachel, Leff, Alexander P, Price, Cathy J, and Crinion, Jennifer T
- Subjects
Adult ,Male ,anomia treatment ,Anomia ,Young Adult ,Reaction Time ,Aphasia ,Humans ,Nervous System Physiological Phenomena ,word retrieval ,Aged ,picture naming ,phonemic cueing ,Original Articles ,Middle Aged ,Magnetic Resonance Imaging ,aphasia ,Semantics ,Stroke ,Treatment Outcome ,Chronic Disease ,Female ,Cues ,Photic Stimulation ,Human - Abstract
See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Naming in aphasia can be facilitated by phonemic cueing, both as an immediate retrieval strategy and as a long-term treatment. Nardo et al. report that immediate and long-term facilitation of naming rely on common neural networks, while whole words and partial cues promote naming via different networks., See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g. initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted—for the first time—a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process. Before and directly after a 6-week anomia treatment programme, 18 chronic aphasic stroke patients completed our functional magnetic resonance imaging protocol—a picture naming task aided by three different types of phonemic cues (whole words, initial phonemes, final phonemes) and a noise-control condition. Patients completed a naming task based on the training materials, and a more general comprehensive battery of language tests both before and after the anomia treatment, to determine the effectiveness and specificity of the therapy. Our results demonstrate that the anomia treatment was effective and specific to speech production, significantly improving both patients’ naming accuracy and reaction time immediately post-treatment (unstandardized effect size: 29% and 17%, respectively; Cohen’s d: 3.45 and 1.83). Longer term gains in naming were maintained 3 months later. Functional imaging results showed that both immediate and long-term facilitation of naming involved a largely overlapping bilateral frontal network including the right anterior insula, inferior frontal and dorsal anterior cingulate cortices, and the left premotor cortex. These areas were associated with a neural priming effect (i.e. reduced blood oxygen level-dependent signal) during both immediate (phonemically-cued versus control-cue conditions), and long-term facilitation of naming (i.e. treated versus untreated items). Of note is that different brain regions were sensitive to different phonemic cue types. Processing of whole word cues was associated with increased activity in the right angular gyrus; whereas partial word cues (initial and final phonemes) recruited the left supplementary motor area, and right anterior insula, inferior frontal cortex, and basal ganglia. The recruitment of multiple and bilateral areas may help explain why phonemic cueing is such a successful behavioural facilitation tool for anomia treatment. Our results have important implications for optimizing current anomia treatment approaches, developing new treatments, and improving speech outcome for aphasic patients.
- Published
- 2017
34. Integrating Visual and Tactile Information in the Perirhinal Cortex
- Author
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Holdstock, JS, Hocking, J, Notley, P, Devlin, JT, and Price, CJ
- Published
- 2009
35. Computational analysis of the enhancement of photoelectrolysis using transition metal dichalcogenide heterostructures.
- Author
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Baker EAD, Pitfield J, Price CJ, and Hepplestone SP
- Abstract
Finding a material with all the desired properties for a photocatalytic water splitter is a challenge yet to be overcome, requiring both a surface with ideal energetics for all steps in the hydrogen and oxygen evolution reactions (HER and OER) and a bulk band gap large enough to mediate said steps. We have instead examined separating these challenges by investigating the energetic properties of two-dimensional transition metal dichalcogenides (TMDCs) that could be used as a surface coating to a material with a large enough bulk band gap. First we investigated the energetics of monolayer MoS
2 and PdSe2 using density functional theory and then investigated how these energetics changed when they were combined into a heterostructure. Our results show that the surface properties were practically (<0.2 eV) unchanged when combined and the MoS2 layer aligns well with the OER and HER. This work highlights the potential of TMDC monolayers as surface coatings for bulk materials that have sufficient band gaps for photocatalytic applications., (Creative Commons Attribution license.)- Published
- 2022
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36. The Scale of Body Connection: A Multisample Study to Examine Sensitivity to Change Among Mind-Body and Bodywork Interventions.
- Author
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Cheng SC, Thompson EA, and Price CJ
- Subjects
- Humans, Psychometrics methods, Reproducibility of Results, Meditation, Mindfulness, Musculoskeletal Manipulations
- Abstract
Purpose: The purpose of this measurement study was to examine the Scale of Body Connection (SBC) sensitivity to change among mind-body or bodywork interventions and to explore the concurrent validity in relation to emotion dysregulation and mindfulness skills. Methods: This study was based on multiple clinical trials that had used the SBC to evaluate changes in body awareness (BA) and bodily dissociation (BD) in response to a mind-body or bodywork intervention. To test for sensitivity to change, t tests were used to examine change and estimate effect sizes. To explore convergent validity, Pearson's product-moment correlations between the SBC subscales and Five-Facet Mindfulness Questionnaire (FFMQ) and Difficulties in Emotion Regulation Scale (DERS) were calculated among a subset of the studies, which also included these measures. Results: The BA and BD scales consistently detected significant positive responses to a range of intervention types (yoga, mindfulness meditation, BA, multimodal therapy, and bodywork), demonstrating SBC sensitivity to change. With a few exceptions, the effect sizes across studies for BA were above 0.35, indicating near moderate-to-large effect sizes. The effect sizes for BD, as a measure of responsiveness, were much smaller than for BA; however, four of the studies had effect sizes between 0.54 and 0.86. Concurrent validity with the DERS was supported by moderate-to-large correlations, and with the FFMQ, it was significant with the BA scale in one included study. Conclusions: The results of this study further establish SBC validity and sensitivity to change across a range of mind-body therapies and confirm prior findings of moderate-to-strong internal consistency reliability. The findings support the use of this brief scale to assess key dimensions of BA and BD in practice and research.
- Published
- 2022
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37. The Effect of Right Temporal Lobe Gliomas on Left and Right Hemisphere Neural Processing During Speech Perception and Production Tasks.
- Author
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Yamamoto AK, Sanjuán A, Pope R, Parker Jones O, Hope TMH, Prejawa S, Oberhuber M, Mancini L, Ekert JO, Garjardo-Vidal A, Creasey M, Yousry TA, Green DW, and Price CJ
- Abstract
Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yamamoto, Sanjuán, Pope, Parker Jones, Hope, Prejawa, Oberhuber, Mancini, Ekert, Garjardo-Vidal, Creasey, Yousry, Green and Price.)
- Published
- 2022
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38. Assessing Cell Competition in Human Pluripotent Stem Cell (hPSC) Cultures.
- Author
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Price CJ and Barbaric I
- Subjects
- Animals, Cell Competition, Flow Cytometry methods, Humans, Mammals, Regenerative Medicine, Induced Pluripotent Stem Cells, Pluripotent Stem Cells
- Abstract
Cell-cell interactions are required for development and homeostasis in multicellular organisms from insects to mammals. A critical process governed by these interactions is cell competition, which functions throughout development to control tissue composition by eliminating cells that possess a lower fitness status than their neighbors. Human pluripotent stem cells (hPSCs) are a key biological tool in modeling human development and offer further potential as a source of clinically relevant cell populations for regenerative medicine applications. Recently, cell competition has been demonstrated in hPSC cultures and during induced pluripotent stem cell reprogramming. In turn, these findings suggest that hPSCs can be used as a tool to study and model cell-cell interactions during different stages of development and disease. Here, we provide a panel of protocols optimized for hPSCs to investigate the potential role that cell competition may have in determining the fate and composition of cell populations during culture. The protocols entail assessment of the competitive phenotype and the mode through which cell competition may lead to elimination of less-fit cells from mosaic cultures with fitter counterparts. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Electroporation of hPSCs to establish a fluorescent reference cell line Support Protocol 1: Single-cell dissociation of hPSCs Support Protocol 2: Single-cell cloning of fluorescently labeled hPSCs Basic Protocol 2: Separate culture and co-culture proliferation assays Basic Protocol 3: Assessing levels of apoptosis in hPSC cultures using flow cytometry Basic Protocol 4: Transwell assay Support Protocol 3: Immunohistochemistry and image quantification of cleaved caspase-3 Basic Protocol 5: Cell confrontation assay Basic Protocol 6: Cell compression assay Basic Protocol 7: Time-lapse imaging to assess mechanical extrusion., (© 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.)
- Published
- 2022
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39. Mindful Body Awareness With Medication Treatment for Opioid Use Disorder
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National Center for Complementary and Integrative Health (NCCIH) and Cynthia Price, Research Professor
- Published
- 2024
40. Dissociating the functions of three left posterior superior temporal regions that contribute to speech perception and production.
- Author
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Ekert JO, Gajardo-Vidal A, Lorca-Puls DL, Hope TMH, Dick F, Crinion JT, Green DW, and Price CJ
- Subjects
- Adult, Cerebellum diagnostic imaging, Cerebral Cortex diagnostic imaging, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net diagnostic imaging, Reading, Temporal Lobe diagnostic imaging, Young Adult, Brain Mapping, Cerebellum physiology, Cerebral Cortex physiology, Nerve Net physiology, Psycholinguistics, Speech physiology, Speech Perception physiology, Temporal Lobe physiology
- Abstract
Prior studies have shown that the left posterior superior temporal sulcus (pSTS) and left temporo-parietal junction (TPJ) both contribute to phonological short-term memory, speech perception and speech production. Here, by conducting a within-subjects multi-factorial fMRI study, we dissociate the response profiles of these regions and a third region - the anterior ascending terminal branch of the left superior temporal sulcus (atSTS), which lies dorsal to pSTS and ventral to TPJ. First, we show that each region was more activated by (i) 1-back matching on visually presented verbal stimuli (words or pseudowords) compared to 1-back matching on visually presented non-verbal stimuli (pictures of objects or non-objects), and (ii) overt speech production than 1-back matching, across 8 types of stimuli (visually presented words, pseudowords, objects and non-objects and aurally presented words, pseudowords, object sounds and meaningless hums). The response properties of the three regions dissociated within the auditory modality. In left TPJ, activation was higher for auditory stimuli that were non-verbal (sounds of objects or meaningless hums) compared to verbal (words and pseudowords), irrespective of task (speech production or 1-back matching). In left pSTS, activation was higher for non-semantic stimuli (pseudowords and hums) than semantic stimuli (words and object sounds) on the dorsal pSTS surface (dpSTS), irrespective of task. In left atSTS, activation was not sensitive to either semantic or verbal content. The contrasting response properties of left TPJ, dpSTS and atSTS was cross-validated in an independent sample of 59 participants, using region-by-condition interactions. We also show that each region participates in non-overlapping networks of frontal, parietal and cerebellar regions. Our results challenge previous claims about functional specialisation in the left posterior superior temporal lobe and motivate future studies to determine the timing and directionality of information flow in the brain networks involved in speech perception and production., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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41. A functional dissociation of the left frontal regions that contribute to single word production tasks.
- Author
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Ekert JO, Lorca-Puls DL, Gajardo-Vidal A, Crinion JT, Hope TMH, Green DW, and Price CJ
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Reading, Brain Mapping methods, Frontal Lobe diagnostic imaging, Frontal Lobe physiology, Magnetic Resonance Imaging, Pattern Recognition, Visual physiology, Speech Production Measurement
- Abstract
Controversy surrounds the interpretation of higher activation for pseudoword compared to word reading in the left precentral gyrus and pars opercularis. Specifically, does activation in these regions reflect: (1) the demands on sublexical assembly of articulatory codes, or (2) retrieval effort because the combinations of articulatory codes are unfamiliar? Using fMRI, in 84 neurologically intact participants, we addressed this issue by comparing reading and repetition of words (W) and pseudowords (P) to naming objects (O) from pictures or sounds. As objects do not provide sublexical articulatory cues, we hypothesis that retrieval effort will be greater for object naming than word repetition/reading (which benefits from both lexical and sublexical cues); while the demands on sublexical assembly will be higher for pseudoword production than object naming. We found that activation was: (i) highest for pseudoword reading [P>O&W in the visual modality] in the anterior part of the ventral precentral gyrus bordering the precentral sulcus (vPCg/vPCs), consistent with the sublexical assembly of articulatory codes; but (ii) as high for object naming as pseudoword production [P&O>W] in dorsal precentral gyrus (dPCg) and the left inferior frontal junction (IFJ), consistent with retrieval demands and cognitive control. In addition, we dissociate the response properties of vPCg/vPCs, dPCg and IFJ from other left frontal lobe regions that are activated during single word speech production. Specifically, in both auditory and visual modalities: a central part of vPCg (head and face area) was more activated for verbal than nonverbal stimuli [P&W>O]; and the pars orbitalis and inferior frontal sulcus were most activated during object naming [O>W&P]. Our findings help to resolve a previous discrepancy in the literature, dissociate three functionally distinct parts of the precentral gyrus, and refine our knowledge of the functional anatomy of speech production in the left frontal lobe., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2021
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42. A Data-Based Approach for Selecting Pre- and Intra-Operative Language Mapping Tasks.
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Ekert JO, Kirkman MA, Seghier ML, Green DW, and Price CJ
- Abstract
Background: Pre- and intra-operative language mapping in neurosurgery patients frequently involves an object naming task. The choice of the optimal object naming paradigm remains challenging due to lack of normative data and standardization in mapping practices. The aim of this study was to identify object naming paradigms that robustly and consistently activate classical language regions and could therefore be used to improve the sensitivity of language mapping in brain tumor and epilepsy patients. Methods: Functional magnetic resonance imaging (fMRI) data from two independent groups of healthy controls (total = 79) were used to generate threshold-weighted voxel-based consistency maps. This novel approach allowed us to compare inter-subject consistency of activation for naming single objects in the visual and auditory modality and naming two objects in a phrase or a sentence. Results: We found that the consistency of activation in language regions was greater for naming two objects per picture than one object per picture, even when controlling for the number of names produced in 5 s. Conclusion: More consistent activation in language areas for naming two objects compared to one object suggests that two-object naming tasks may be more suitable for delimiting language eloquent regions with pre- and intra-operative language testing. More broadly, we propose that the functional specificity of brain mapping paradigms for a whole range of different linguistic and non-linguistic functions could be enhanced by referring to databased models of inter-subject consistency and variability in typical and atypical brain responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ekert, Kirkman, Seghier, Green and Price.)
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- 2021
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43. Auditory training changes temporal lobe connectivity in ‘Wernicke’s aphasia’: a randomised trial
- Author
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Woodhead, ZVJ, Crinion, J, Teki, S, Penny, W, Price, CJ, and Leff, AP
- Abstract
Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.
- Published
- 2017
44. Erratum to: Reply: Broca's area: why was neurosurgery neglected for so long when seeking to re-establish the scientific truth? and Where is the speech production area? Evidence from direct cortical electrical stimulation mapping.
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Lorca-Puls DL, Gajardo-Vidal A, Green DW, and Price CJ
- Published
- 2021
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45. Brain regions that support accurate speech production after damage to Broca's area.
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Lorca-Puls DL, Gajardo-Vidal A, Oberhuber M, Prejawa S, Hope TMH, Leff AP, Green DW, and Price CJ
- Abstract
Broca's area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca's area. Importantly, contemporary evidence suggests that, within Broca's area, its posterior part (i.e. pars opercularis) plays a more prominent role in speech production than its anterior part (i.e. pars triangularis). In this study, we therefore investigated the brain activation patterns that underlie accurate speech production following stroke damage to the opercular part of Broca's area. By combining functional MRI and 13 tasks that place varying demands on speech production, brain activation was compared in (i) seven patients of interest with damage to the opercular part of Broca's area; (ii) 55 neurologically intact controls; and (iii) 28 patient controls with left-hemisphere damage that spared Broca's area. When producing accurate overt speech responses, the patients with damage to the left pars opercularis activated a substantial portion of the normal bilaterally distributed system. Within this system, there was a lesion-site-dependent effect in a specific part of the right cerebellar Crus I where activation was significantly higher in the patients with damage to the left pars opercularis compared to both neurologically intact and patient controls. In addition, activation in the right pars opercularis was significantly higher in the patients with damage to the left pars opercularis relative to neurologically intact controls but not patient controls (after adjusting for differences in lesion size). By further examining how right Crus I and right pars opercularis responded across a range of conditions in the neurologically intact controls, we suggest that these regions play distinct roles in domain-general cognitive control. Finally, we show that enhanced activation in the right pars opercularis cannot be explained by release from an inhibitory relationship with the left pars opercularis (i.e. dis-inhibition) because right pars opercularis activation was positively related to left pars opercularis activation in neurologically intact controls. Our findings motivate and guide future studies to investigate (i) how exactly right Crus I and right pars opercularis support accurate speech production after damage to the opercular part of Broca's area and (ii) whether non-invasive neurostimulation to one or both of these regions boosts speech production recovery after damage to the opercular part of Broca's area., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2021
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46. Lesion site and therapy time predict responses to a therapy for anomia after stroke: a prognostic model development study.
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Hope TMH, Nardo D, Holland R, Ondobaka S, Akkad H, Price CJ, Leff AP, and Crinion J
- Subjects
- Anomia diagnosis, Brain pathology, Disease Management, Female, Humans, Male, Prognosis, Anomia etiology, Anomia therapy, Stroke complications
- Abstract
Stroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger in some patients than others. Here, we asked whether that variation might be more systematic, and even predictable, than previously thought. 18 patients, each at least 6 months after left hemisphere stroke, engaged in a computerised treatment for their anomia over a 6-week period. Using only: (a) the patients' initial accuracy when naming (to-be) trained items; (b) the hours of therapy that they devoted to the therapy; and (c) whole-brain lesion location data, derived from structural MRI; we developed Partial Least Squares regression models to predict the patients' improvements on treated items, and tested them in cross-validation. Somewhat surprisingly, the best model included only lesion location data and the hours of therapy undertaken. In cross-validation, this model significantly out-performed the null model, in which the prediction for each patient was simply the mean treatment effect of the group. This model also made promisingly accurate predictions in absolute terms: the correlation between empirical and predicted treatment response was 0.62 (95% CI 0.27, 0.95). Our results indicate that individuals' variation in response to anomia treatment are, at least somewhat, systematic and predictable, from the interaction between where and how much lesion damage they have suffered, and the time they devoted to the therapy., (© 2021. The Author(s).)
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- 2021
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47. Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition.
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Price CJ, Stavish D, Gokhale PJ, Stevenson BA, Sargeant S, Lacey J, Rodriguez TA, and Barbaric I
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Cells, Cultured, Cytoplasm metabolism, Humans, Transcription Factors metabolism, Cell Competition genetics, Cell Differentiation genetics, Cell Proliferation genetics, Pluripotent Stem Cells cytology, YAP-Signaling Proteins metabolism
- Abstract
The appearance of genetic changes in human pluripotent stem cells (hPSCs) presents a concern for their use in research and regenerative medicine. Variant hPSCs that harbor recurrent culture-acquired aneuploidies display growth advantages over wild-type diploid cells, but the mechanisms that yield a drift from predominantly wild-type to variant cell populations remain poorly understood. Here, we show that the dominance of variant clones in mosaic cultures is enhanced through competitive interactions that result in the elimination of wild-type cells. This elimination occurs through corralling and mechanical compression by faster-growing variants, causing a redistribution of F-actin and sequestration of yes-associated protein (YAP) in the cytoplasm that induces apoptosis in wild-type cells. YAP overexpression or promotion of YAP nuclear localization in wild-type cells alleviates their "loser" phenotype. Our results demonstrate that hPSC fate is coupled to mechanical cues imposed by neighboring cells and reveal that hijacking this mechanism allows variants to achieve clonal dominance in cultures., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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48. Facilitating Adaptive Emotion Processing and Somatic Reappraisal via Sustained Mindful Interoceptive Attention.
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Price CJ and Weng HY
- Abstract
Emotions are by nature embodied, as the brain has evolved to quickly assess the emotional significance of stimuli and output signals to the body's viscera and periphery to aid adaptive responses. Emotions involve both implicit bodily and explicit narrative processes, and patients may experience transdiagnostic distress when bodily signals are not attended to and holistically integrated with explicit narratives about experience. Similarly, therapists may be trained in more implicit body-based approaches (i.e., massage/bodywork, physical and occupational therapy, and nursing/medicine) or more explicit narrative-based approaches (i.e., psychotherapy), and may lack training in skills that integrate both levels of emotion processing to aid healing and growth. To address these gaps, we propose a framework where the bridge between implicit bodily sensations and explicit narratives lies in cultivating mindful awareness of bodily sensations associated with emotions. This process brings subjective awareness to notice inner body experience (or interoceptive awareness) that is often outside of conscious awareness, so that it may be understood and re-integrated in more adaptive ways, which we call somatic reappraisal. Using clinical theory and example vignettes, we present mindful interoceptive awareness for adaptive emotion processing as a framework to cultivate and enhance somatic reappraisal. Mindful interoceptive awareness brings more focused and sustained attention to inner body experience; likewise, internal sensations associated with emotions become more granular, vivid, and can shift in ways that facilitate somatic reappraisal. Learning to sustain interoceptive awareness when engaged with mindfulness qualities of nonjudgment and compassion promotes an experience where new associations between emotions, meanings, and memories can be made that generate insights that are holistic and integrative. A clinical vignette is used in this paper to provide examples of this approach in psychotherapy. An example script for use in mindfulness groups is included, and resources are suggested for clinicians to gain more experience. Mindful interoceptive awareness for adaptive emotion processing is a clinical process that can be learned and applied by a range of clinicians to treat mental and physical health conditions that may benefit greater embodied awareness., Competing Interests: CP serves as the director of the Center for Mindful Body Awareness, a 501c3 organization that provides educational trainings in the mindful awareness in body-oriented therapy (MABT) approach to therapists/practitioners in the community, at academic institutions, and in clinical settings. The Center also develops, implements, and evaluates programs involving the practice of interoceptive awareness practice in collaboration with community or academic clinical settings. There are no other disclosures reported. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Price and Weng.)
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- 2021
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49. Reply: Broca's area: why was neurosurgery neglected for so long when seeking to re-establish the scientific truth? and Where is the speech production area? Evidence from direct cortical electrical stimulation mapping.
- Author
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Lorca-Puls DL, Gajardo-Vidal A, Green DW, and Price CJ
- Subjects
- Broca Area, Electric Stimulation, Frontal Lobe, Humans, Neurosurgery, Speech
- Published
- 2021
- Full Text
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50. Tolerability and age-dependent toxicokinetics following perinatal hydroxyurea treatment in Sprague Dawley rats.
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Huang MC, Turner KJ, Vallant M, Robinson VG, Lu Y, Price CJ, Fennell TR, Silinski MA, Waidyanatha S, Ryan KR, Black SR, Fernando RA, and McIntyre BS
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- Animals, Animals, Newborn, Body Weight drug effects, Female, Hydroxyurea pharmacology, Lactation drug effects, Male, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Rats, Sprague-Dawley, Reproduction drug effects, Antisickling Agents toxicity, Hydroxyurea toxicity, Toxicokinetics
- Abstract
Hydroxyurea (HU) is a valuable therapy for individuals with sickle cell anemia. With increased use of HU in children and throughout their lives, it is important to understand the potential effects of HU therapy on their development and fertility. Thus, studies were conducted to identify appropriate doses to examine long-term effects of prenatal and early postnatal HU exposure and to understand kinetics of HU at various life stages. Pregnant Sprague Dawley dams were administered HU (0-150 mg/kg/day) via oral gavage from gestation days 17 to 21 and during lactation. Pups were dosed with the same dose as their respective dam starting on postnatal day (PND) 10 and up to PND 34. There was minimal maternal toxicity, and no significant effects on littering at any dose of HU. Starting on ~PND 16, offspring displayed skin discoloration and alopecia at doses ≥75 mg/kg/day and lower body weight compared to controls at doses ≥100 mg/kg/day. Gestational transfer of HU was observed, but there was minimal evidence of lactational transfer. Our toxicokinetic studies suggest that the internal dose in offspring may be altered due to age, but not due to sex. The plasma area under the curve, a measure of systemic exposure, at doses tolerated by offspring was threefold to sevenfold lower than the internal therapeutic dose in humans. Therefore, strategies to establish clinically relevant exposures in animal studies are needed. Overall, these data are useful for the design of appropriate nonclinical studies in the future to evaluate the consequences of long-term HU treatment starting in childhood., (© 2020 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
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