55 research outputs found
sj-docx-1-jop-10.1177_02698811221092506 – Supplemental material for Individual and combined effects of cannabidiol and Δ9-tetrahydrocannabinol on striato-cortical connectivity in the human brain
No full textSupplemental material, sj-docx-1-jop-10.1177_02698811221092506 for Individual and combined effects of cannabidiol and Δ9-tetrahydrocannabinol on striato-cortical connectivity in the human brain by Matthew B Wall, Tom P Freeman, Chandni Hindocha, Lysia Demetriou, Natalie Ertl, Abigail M Freeman, Augustus PM Jones, Will Lawn, Rebecca Pope, Claire Mokrysz, Daniel Solomons, Ben Statton, Hannah R Walker, Yumeya Yamamori, Zixu Yang, Jocelyn LL Yim, David J Nutt, Oliver D Howes, H Valerie Curran and Michael AP Bloomfield in Journal of Psychopharmacology</p
Effects of Sustained D2 Receptors Blockade on Brain Structure and Function in Healthy Volunteers
No full textTBackground
The effect of D2 Receptor (D2R) blockade, exerted by antipsychotics, on brain structure and function is still under debate. Studies in patients reported mixed results with difficulties in separating disease and treatment effects. Single-dose studies in healthy volunteers (HV) have shown no change or reduction in striatal volumes, increased striatal cerebral blood flow (CBF) and reduced cortico-striatal functional connectivity (FC). However, it remains unclear whether these effects are stable after prolonged D2R blockade and how do they relate to extrapyramidal symptoms (EPS).
Methods
A total of 37 HV (15 females) entered a double-blinded, randomized, crossover, placebo-controlled study. Participants received either amisulpride 400mg or placebo daily for seven days. T1-maps and brain volume estimation were derived from MP2RAGE sequence. PCASL and resting-state multi-echo fMRI sequences were used to assess CBF and FC respectively. Voxel-wise permutation-based paired t-test as in FSL randomise was used to test drug effects (TFCE correction). We tested the association between drug effects and EPS (ESRS scale) using Spearman correlation. Analyses were performed on all subjects with available data.
Results
We did not find voxel-wise differences between amisulpride and placebo in both T1-maps and brain volumes. Amisulpride increased CBF in the striatum and reduced FC between its sensorimotor subdivision and the primary motor cortex as compared with placebo. Greater reduction in functional connectivity was associated with greater EPS (R2= 0.33, p= 0.018).
Conclusions
Our results indicate that functional alteration in the striatum persist after sustained D2R blockade without structural changes and could potentially serve as a biomarker for EPS
Antipsychotics cause reversible structural brain changes within one week
No full text: Determining the effects of antipsychotics on MRI brain structural metrics without the potential confounding effects related to the natural course of a psychotic illness is challenging. However, it is crucial to understand these effects to interpret the results of cross-sectional and longitudinal studies in medicated patients and, ultimately, to understand better the biological mechanisms driving antipsychotics' effects. In this work, we aim to determine whether exposure to antipsychotics is associated with alterations in brain MRI structural metrics in the absence of disease effects. A randomized, double-blind, counter-balanced order, crossover, placebo-controlled study in healthy volunteers was performed. The study comprised two arms. Within arms, participants were randomized to receive daily doses of either the active compound (Arm 1= amisulpride 400 mg/day, N = 24; Arm 2= aripiprazole 10 mg/day, N = 24) for one week, followed by placebo or vice versa. We found increased MRI volume estimates in the left putamen and in the right caudate in the amisulpride condition as compared to placebo and increased right putamen volume estimates after aripiprazole compared to placebo. No other effects were found in cortical volume estimates, cortical thickness, cortical surface area, and T1-relaxation time. Striatal changes reversed within weeks of drug withdrawal. Short-term exposure to either one of two different antipsychotics results in a transient increase in striatal volume measured with T1-weighted MRI that normalizes rapidly on stopping treatment without cortical changes. Our findings suggest that striatal volumetric MRI differences detected in people with schizophrenia taking antipsychotics are, at least in part, attributable to pharmacological effects
The holistic nature of literary knowledge : a perspective of authorial meaning and legitimate significance as a unique aesthetic experience
No full textLiterary knowledge represents the state of affairs in the holistic nature of literature. Within the scheme of co-ordinates that constitute the holistic nature of literature, legitimate aesthetic experience cannot occur unless a valid interpretation of meaning is considered as the probable intention of the author. Understanding meaning initiates legitimate aesthetic experience as opposed to an aesthetic awareness that inadvertently distorts authorial intention to satisfy wishfulfilment gratification of the audience. Validity in interpretation implies satisfying the conditions of knowledge, in that agreement in .judgements about literature is possible. Yet, though meaning may satisfy the conditions of objectivity, each legitimate aesthetic experience is peculiar to the individual's empathic relationship to the valid interpretation. . The significance of the text may be an ineffable aesthetic experience which is a self-evident form of knowledge. The synthesis of Hirsch's theory of 'meaning and 'significance' with Hirst's belief that literature is ? 'unique form of knowledge' gives a dual nature to, and foundation for, the epistemological status of literature. Consequently, there is justification for teaching literary knowledge in texts and procedural knowledge for construal of valid interpretation. Interpretation and criticism have different functions. One attempts to give coherence and objectivity to textual meaning, while criticism imbues a valid interpretation with a 'unique' knowledge that is relative to the dynamic of history and the dialectic of criticism. If students are to perceive in some degree the holistic nature of literary knowledge, then trainee teachers ought to be familiar with the synthesis of Hirsch and Hirst which is a primary principle both in the construal of textual meaning and in the attempt to express legitimate aesthetic experience
Book Reviews
No full textBook Review 1Book Title: J.A.M.A. Clinical Abtracts of Diagnosis and TreatmentBook Author: Published with the Approval of the Board of Trustees, American Medical AssociationPp. 627 + vi. 85.50. London and New York: Grune and Statton, Inc. 1955.Book Review 2Book Title: The British Encyclopaedia of Medical Practice, Including Medicine, Surgery, Obstetrics, Gynaecology and other Special Subjects: Medical Progress 1955Book Author: Editor in Chief: The Lord HorderPp. 311 + vi. London: Butterworth & Co. (Publishers), Ltd., South African Office-Butterworth & Co. (Africa) Ltd., Durban. 1955.Book Review 3Book Title: The Pocket Prescriber and Guide to Prescription WritingBook Author: Alistair G. CruikshankE. & S. Livingstone Ltd., Edinburgh and London. 1956.Book Review 4Book Title: The Year Book of Obstetrics & GynecologyBook Author: J.P. Greenhill (Ed.)1955-1956 Series (pp. 544). Chicago: The Year Book Publishers, Inc.Book Review 5Book Title: Topley and Wilson's Principles of Bacteriology and Immunity. Fourth Edition. Volumes I and II.Book Authors: G.S. Wilson & A.A. MilesPp. 2331 + cxv. £8 0s. 0d. set of two Volumes. London: Edward Arnold (publishers) Ltd. 1955.Book Review 6Book Title: Is That You Doctor? Tabloids out of the Medical BagBook Author: lmhotepPp. 207 + xi with illustrations. 15s. 0d. Cape Town Howard B. Timmins. 1955
Identifying critical recruitment bottlenecks limiting seedling establishment in a degraded seagrass ecosystem /631/158/854 /704/158/1745 article
No full text© 2017 The Author(s). Identifying early life-stage transitions limiting seagrass recruitment could improve our ability to target demographic processes most responsive to management. Here we determine the magnitude of life-stage transitions along gradients in physical disturbance limiting seedling establishment for the marine angiosperm, Posidonia australis. Transition matrix models and sensitivity analyses were used to identify which transitions were critical for successful seedling establishment during the first year of seed recruitment and projection models were used to predict the most appropriate environments and seeding densities. Total survival probability of seedlings was low (0.001), however, transition probabilities between life-stages differed across the environmental gradients; seedling recruitment was affected by grazing and bioturbation prevailing during the first life-stage transition (1 month), and 4-6 months later during the third life-stage transition when establishing seedlings are physically removed by winter storms. Models projecting population growth from different starting seed densities showed that seeds could replace other more labour intensive and costly methods, such as transplanting adult shoots, if disturbances are moderated sufficiently and if large numbers of seed can be collected in sufficient quantity and delivered to restoration sites efficiently. These outcomes suggest that by improving management of early demographic processes, we could increase recruitment in restoration programs
Patient-specific modelling of pulmonary arterial hypertension: wall shear stress correlates with disease severity
No full textIntroduction: Pulmonary arterial hypertension (PAH) requires an invasive right heart catheter (RHC) procedure for diagnosis. Patients can present with initial symptoms and interact with healthcare institutes for up to three years before referral for diagnosis. Thus, there is a great need to develop noninvasive tools, to better screen patients and improve early diagnosis rates. Methods: seven patients diagnosed and treated for PAH were included in this study. Patient-specific computational fluid dynamics (CFD) models were built for all patients, with all model parameters tuned using non-invasive imaging data, including CT, cardiac MR, echocardiogram, and 4D-flow MRI scanscrucially, a 3D inlet velocity profile was derived from 4D-flow MRI. Results: CFD models were quantitatively and qualitatively well matched with in-vivo 4D-flow hemodynamics. A linear correlation of R 2 = 0.84 was found between CFD derived time-averaged wall shear stress (TAWSS) and RHC measured mean pulmonary pressure (key diagnostic value): low TAWSS correlated with high pressure. Conclusions: This study highlights TAWSS as a potential computational biomarker for PAH. The clinical use of TAWSS to diagnose and stratify PAH patients has the potential to greatly improve patient outcomes. Further work is ongoing to validate these findings in larger cohorts
Temperature dependence, accuracy, and repeatability of T-1 and T-2 relaxation times for the ISMRM/NIST system phantom measured using MR fingerprinting
No full textPurpose
Before MR fingerprinting (MRF) can be adopted clinically, the derived quantitative values must be proven accurate and repeatable over a range of T1 and T2 values and temperatures. Correct assessment of accuracy and precision as well as comparison between measurements can only be performed when temperature is either controlled or corrected for. The purpose of this study was to investigate the temperature dependence of T1 and T2 MRF values and evaluate the accuracy and repeatability of temperature-corrected relaxation values derived from a B1-corrected MRF–fast imaging with steady-state precession implementation using 2 different dictionary sizes.
Methods
The International Society of MR in Medicine/National Institute of Standards and Technology phantom was scanned using an MRF sequence of 2 different lengths, a variable flip angle T1, and a multi-echo spin echo T2 at 14 temperatures ranging from 15°C to 28°C and investigated with a linear regression model. Temperature-corrected accuracy was evaluated by correlating T1 and T2 times from each MRF dictionary with reference values. Repeatability was assessed using the coefficient of variation, with measurements taken over 30 separate sessions.
Results
There was a statistically significant fit of the model for MRF-derived T1 and T2 and temperature (p 500 ms. Both MRF methods showed a strong linear correlation with reference values for T1 (R2 = 0.996) and T2 (R2 = 0.982). MRF repeatability for T1 values was ≤1.4% and for T2 values was ≤3.4%.
Conclusion
MRF demonstrated relaxation times with a temperature dependence similar to that of conventional mapping methods. Temperature-corrected T1 and T2 values from both dictionaries showed adequate accuracy and excellent repeatability in this phantom study
Motion-corrected multiparametric renal arterial spin labelling at 3T: Reproducibility and effect of vasodilator challenge
No full textObjectives
We investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T1.
Methods
In a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T1 were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots.
Results
Inter-study correlation of whole-kidney RBF was good for both single-TI (r2 = 0.90), and multi-TI ASL (r2 = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T1 of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant.
Conclusions
Free-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge
Establishing cardiac MRI reference ranges stratified by sex and age for cardiovascular function during exercise
No full textPurpose: To evaluate the effects of exercise on left ventricular parameters using exercise cardiac MRI in healthy adults without known cardiovascular disease, and establish reference ranges stratified by age and sex.
Materials and Methods: This prospective study included healthy adult participants with no known cardiovascular disease or genetic variants associated with cardiomyopathy, enrolled between January 2018 and April 2021, who underwent exercise cardiac MRI evaluation. Participants were imaged at rest and after exercise, with parameters measured by two readers. Prediction intervals were calculated and compared across sex and age groups.
Results: The study included 161 participants (mean age, 49±[SD]14 years; 85 female). Compared with the resting state, exercise caused an increase in heart rate (64±9 bpm vs 133±19 bpm, P < 0.001), left ventricular end-diastolic volume (140±32 ml vs 148±35 ml, P < 0.001), stroke volume (82±18 ml vs 102±25 ml, P < 0.001), ejection fraction (59±6% vs 69±7%, P < 0.001), and cardiac output (5.2±1.1 l/min vs 13.5±3.9 l/min, P < 0.001), and a decrease in left ventricular end-systolic volume (58±18 ml vs 46±15 ml, P < 0.001). There were significant differences in exercise response between groups stratified by sex and age for most parameters.
Conclusion: In healthy adults, an increase in cardiac output after exercise is driven by a rise in heart rate with both increased ventricular filling and emptying. Normal ranges for exercise response, stratified by age and sex, are established as a reference for the use of exercise cardiac MRI in clinical practice
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