Cardiac Magnetic Resonance T1 Mapping in Cardiomyopathies

Cardiac magnetic resonance (CMR) imaging has been widely used to assess myocardial perfusion and scar and is the noninvasive reference standard for identification of focal myocardial fibrosis. However, the late gadolinium enhancement (LGE) technique is limited in its accuracy for absolute quantification and assessment of diffuse myocardial fibrosis by technical and pathophysiological features. CMR relaxometry, incorporating T1 mapping, has emerged as an accurate, reproducible, highly sensitive, and quantitative technique for the assessment of diffuse myocardial fibrosis in a number of disease states. We comprehensively review the physics behind CMR relaxometry, the evidence base, and the clinical applications of this emerging technique

Neurochemical enhancement of conscious error awareness

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited.Weconducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Brain mapping of acupuncture effects using functional magnetic resonance imaging

There remains a high degree of scepticism about acupuncture since its theoretical basis has no clear reference in Western medical and scientific terms, making any associations between neurophysiology and specific acupuncture concepts difficult to determine. Using neuroimaging and engineering approaches to understand its physiological basis may engender greater acceptance of and improvement in the clinical application of acupuncture. Research into the efficacy of acupuncture has raised a number of difficult methodological issues, particularly in relation to the selection of appropriate controls. Separating specific effects from non-specific effects is complex because acupuncture is a physical, invasive, manual procedure involving time and ritual. Sham acupuncture results show only the difference between sham and real acupuncture not the real affect of acupuncture, and other controls may produce distinct subjective and objective effects. Point injection (the injection of a small amount of a substance at an acupoint), a recent innovation of traditional acupuncture, aims to enhance and prolong the stimulation effect in a standardised, reproducible manner. By providing precise, measurable acupoint stimulation applied incrementally in a specifically designed paradigm, an acupoint could act as its own control. This firstly requires injection to be validated against traditional needling. Aims 1. To develop an instrument for reproducible saline delivery at an acupoint. 2. To cross-validate saline acupoint injection (PI) with traditional needle acupuncture (TA). 3. To demonstrate central nervous system (CNS) effects of acupuncture both in health and chronic pain. Hypothesis The primary hypothesis is that stimulation of specific acupoints with linearly incremental saline injection produces differential effects within the CNS observable with functional magnetic resonance imaging (fMRI) allowing investigation of acupuncture in health and chronic pain. Novelty As neuroimaging has not yet clearly defined the brain structures that may be modulated by acupuncture, this project is exploratory in nature. It is expected that acupuncture effects can be robustly imaged with fMRI in healthy subjects and those suffering chronic pain. The demonstrated effects will result from the acupuncture process of progressive point stimulation by tissue distension rather than needle insertion or biological noise. It is proposed to examine the putative modulation of pain by acupuncture within the extensively mapped neuromatrix of cortical and subcortical regions, including the somatic, insula, and limbic cortices, and thalamus. Detailed information regarding differences in brain response between acupuncture in normal and diseased states will expand understanding of acupuncture as a clinical tool. The dilemma of sham stimulation or arbitrary controls will be addressed by confirming PI as a valid, reproducible stimulation method. Methods and Results A series of empirical experiments was designed and conducted to determine the effects of stimulation of different acupoints. 1. Chapters 1 and 3 outline the current understanding of acupuncture in the Western milieu and a review of the neuroimaging literature respectively. 2. In Chapter 2, the report of PI tested against TA in healthy volunteers to determine equivalence of physiological effect demonstrates no statistically significant differences between the methodologies. 3. Chapter 4 reports the design and validation of a task specific microprocessor controlled syringe driver. 4. Four differing acupoints were tested during an fMRI experiment described in Chapter 5; different activation areas were demonstrated across the acupoints providing early support for the hypothesis that different acupoints may have different effects. A subset of brain areas recognised within the pain neuromatrix was delineated, congruent spatially and directionally with those reported in pharmacological analgesia studies. 5. As outlined in Chapter 6, heart rate variability can be measured rapidly in a stressful environment to provide meaningful data on the response of the autonomic nervous system to acupuncture stimulation. 6. The hypothesis of different acupoints having different effects was tested in subjects suffering chronic pain by contrasting an accepted and a neutral acupoint, the results being reported in Chapter 7. Conclusion Despite a long history of clinical usage, appropriate scientific studies have not yet addressed the basic effectiveness and efficacy of acupuncture. This thesis presents a series of empirical studies designed to address a number of the questions arising in the literature and provides converging evidence of the manner in which different acupoints modulate the CNS, specifically within the pain neuromatrix

Selected immunoendocrine measures for monitoring responses to training and match load in professional association football: A review of the evidence

Biomarkers relating to player stress balance, immunological (ie, immunoglobulin-A), and hormonal (ie, testosterone and cortisol [T : C]) status are now commonly used in football. This article is our critical review of the scientific literature relating to the response of these measures to player load and their relationships with player health. The commonly reported relationship between immunoglobulin-A and training or match load highlights its sensitivity to changes in psychophysiological stress and the increased risk of compromised mucosal immunity. This is supported by its close relationship with symptoms of upper respiratory tract infection and its association with perceived fatigue in football players. Testosterone and cortisol concentrations and the testosterone-cortisol ratio are sensitive to changes in player load, but the direction of their response is often inconsistent and is likely influenced by player training status and non-sport-related stressors. Some evidence indicates that sustained periods of high training volume can increase resting testosterone and that sustained periods of low and high training intensity can increase resting cortisol, compromising the testosterone-cortisol ratio. These findings are noteworthy, as recent findings indicate interrelationships between testosterone, cortisol, and testosterone:cortisol and perceived measures of fatigue, sleep quality, and muscle soreness in football players. Variability in individual responses suggests the need for a multivariate and individualized approach to player monitoring. Overall, we consider that there is sufficient evidence to support the use of salivary immunoglobulin-A, testosterone, cortisol, and testosterone:cortisol measures as part of a multivariate, individualized player monitoring system in professional football

Oxidation of silicon and non-equilibrium segregation of boron during redistribution

The oxidation of silicon and the diffusion of boron into siliconhave been investigated together with device manufacturing proceduresin the microelectronics laboratory at the University of New SouthWales .A number of silicon wafers were oxidised at a fixed temperature forvarious times following thorough chemical cleaning and the resultant oxidethicknesses were measured using a Tolansky microscope. Fromthe experimental results an equation relating the oxide thickness tothe oxidation time (at 1100'C) was derived using the method of leastsquares. The experimental oxidation curve is in agreement with otherworks .In an attempt to characterise the diffusion of boron in silicon afurther four wafers were subjected to boron predepositions anddrive-ins, the drive-ins being performed in oxygen. Sheet resistivitymeasurements, made with a four point probe after the predepositions,agree with general trends established elsewhere. The redistributionof boron during thermal oxidation was then examined and three boronconcentration profiles were obtained. These profiles indicated thatsurface depletion of boron had occurred as a result of the thermaloxidation, the degree of surface depletion being dependent on thedrive--in conditions.To determine the concentration profiles each wafer was subjected to anetch, weigh and resistivity measurement sequence from which the boronconcentration as a function of depth into the silicon was calculated.The methods used were systematically refined as the work proceededand all have been documented in the appendices.Finally, the theory of the redistribution of boron during oxidationwas examined in conjunction with a closed form solution to theredistribution problem by Huang & Welliver (Ref.11).Their diffusion model was found to be inaccurate and a refinement wasmade with the introduction of a reaction-rate constant, resulting ina mathematical model which appears to describe the redistribution ofboron more correctly.In conclusion, the thesis contains(i) successful step-by-step procedures for many solid-statedevice production process(ii) a silicon oxidation characteristic showing the relationshipbetween oxide thickness and oxidation time at 1100'C(iii) the results of boron predepositions and drive-ins includingboron concentration profiles(iv) a modification to the model for the redistribution of boronduring thermal oxidation as described by Huang & Welliver

Comparison of two-dimensional speckle and tissue velocity based strain and validation with harmonic phase magnetic resonance imaging

Two-dimensional (2-D) strain (epsilon(2-D)) on the basis of speckle tracking is a new technique for strain measurement. This study sought to validate epsilon(2-D) and tissue velocity imaging (TVI)based strain (epsilon(TVI)) with tagged harmonic-phase (HARP) magnetic resonance imaging (MRI). Thirty patients (mean age. 62 +/- 11 years) with known or suspected ischemic heart disease were evaluated. Wall motion (wall motion score index 1.55 +/- 0.46) was assessed by an expert observer. Three apical images were obtained for longitudinal strain (16 segments) and 3 short-axis images for radial and circumferential strain (18 segments). Radial epsilon(TVI) was obtained in the posterior wall. HARP MRI was used to measure principal strain, expressed as maximal length change in each direction. Values for epsilon(2-D), epsilon(TVI), and HARP MRI were comparable for all 3 strain directions and were reduced in dysfunctional segments. The mean difference and correlation between longitudinal epsilon(2-D) and HARP MRI (2.1 +/- 5.5%, r = 0.51, p < 0.001) were similar to those between longitudinal epsilon(TVI), and HARP MRI (1.1 +/- 6.7%, r = 0.40, p < 0.001). The mean difference and correlation were more favorable between radial epsilon(2-D) and HARP MRI (0.4 +/- 10.2%, r = 0.60, p < 0.001) than between radial epsilon(TVI), and HARP MRI (3.4 +/- 10.5%, r = 0.47, p < 0.001). For circumferential strain, the mean difference and correlation between epsilon(2-D) and HARP MRI were 0.7 +/- 5.4% and r = 0.51 (p < 0.001), respectively. In conclusion, the modest correlations of echocardiographic and HARP MRI strain reflect the technical challenges of the 2 techniques. Nonetheless, epsilon(2-D) provides a reliable tool to quantify regional function, with radial measurements being more accurate and feasible than with TVI. Unlike epsilon(TVI), epsilon(2-D) provides circumferential measurements. (c) 2006 Elsevier Inc. All rights reserved