Functional CT Imaging for Myocardial Salvage in Acute Myocardial Infarction Management

Hospitalization and revascularization treatment for patients with acute myocardial infarction (AMI) is an economic burden that can be minimized by identifying patients most likely to benefit. To this end, a non-invasive imaging technique to better characterize myocardial salvage may be helpful. In this thesis work, a functional CT technique is examined to assess at-risk, infarcted, and salvageable myocardial tissue. Data was acquired on a cohort of seven pigs with induced AMI during the acute and sub-acute phases post insult. The tracer kinetic model dependent CT images were validated against both T2-TIRM images and quantitative T1-maps acquired using MRI, as well as constant infusion CT images. Extravascular contrast distribution volume (ECDV) and myocardial perfusion (MP) parameters were used to characterize the injured myocardium. Derived ECDV and MP threshold for acute phase MI in seven pigs is 0.36 ml/g and 0.44 ml/min/g, respectively. Average MP in normal, at-risk and infarcted myocardium were 0.92 0.27, 0.80 0.19, 0.30 0.08 ml/min/g, respectively. Average ECDV in normal, at-risk, and infarcted myocardium were 0.13 0.08, 0.21 0.07, 0.60 0.12 ml/g, respectively. Significance was demonstrated in both MP and ECDV measurements between infarcted myocardium and myocardium atrisk, as well as between infarcted and normal myocardium (p\u3c 0.01). Based on the area estimated using ECDV and MP, at-risk, infarcted, and salvageable myocardial tissue can be delineated

Exploration of the pathophysiological mechanisms underlying hemodialysis associated cardiac ischemic injury

Hemodialysis (HD) provides life-saving treatment in individuals with kidney failure. However, HD is associated with poor quality of life and extremely high mortality rates mainly caused by cardiovascular disease due to heart failure and sudden cardiac death. Standard pharmacological treatment developed within the non-kidney disease community are largely ineffective in HD patients because of the difference in pathophysiology of cardiovascular mortality. HD treatment causes hypotension and recurrent ischemic injury to multiple vascular beds including the heart, leading to heart failure. These injuries can be abrogated by improving the patient’s tolerability of the treatment. To apply interventions that may improve hemodynamic tolerability of HD, it is crucial to understand the mechanisms of HD-induced injury at every layer of the vasculature: the endothelial, microvasculature and macrovasculature. The purpose of this thesis was to study the endothelial and vascular dysfunction effecting tissue perfusion as a result of HD and under conditions of intradialytic exercise and alteration of dialysate sodium concentration

Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis.

How pathogenic cluster of differentiation 4 (CD4) T cells in rheumatoid arthritis (RA) develop remains poorly understood. We used Nur77-a marker of T cell antigen receptor (TCR) signaling-to identify antigen-activated CD4 T cells in the SKG mouse model of autoimmune arthritis and in patients with RA. Using a fluorescent reporter of Nur77 expression in SKG mice, we found that higher levels of Nur77-eGFP in SKG CD4 T cells marked their autoreactivity, arthritogenic potential, and ability to more readily differentiate into interleukin-17 (IL-17)-producing cells. The T cells with increased autoreactivity, nonetheless had diminished ex vivo inducible TCR signaling, perhaps reflective of adaptive inhibitory mechanisms induced by chronic autoantigen exposure in vivo. The enhanced autoreactivity was associated with up-regulation of IL-6 cytokine signaling machinery, which might be attributable, in part, to a reduced amount of expression of suppressor of cytokine signaling 3 (SOCS3)-a key negative regulator of IL-6 signaling. As a result, the more autoreactive GFPhi CD4 T cells from SKGNur mice were hyperresponsive to IL-6 receptor signaling. Consistent with findings from SKGNur mice, SOCS3 expression was similarly down-regulated in RA synovium. This suggests that despite impaired TCR signaling, autoreactive T cells exposed to chronic antigen stimulation exhibit heightened sensitivity to IL-6, which contributes to the arthritogenicity in SKG mice, and perhaps in patients with RA

Older drivers in Australia and advanced vehicle technologies : what are their opinions? : a qualitative study

Background: There is limited research on older drivers’ perspectives on advanced vehicle technologies (AVTs). This study investigates what older drivers know and understand about AVTs in the current vehicle market, and identifies what motivates older drivers to use or not use AVTs. Method: Older drivers (≥65 years) living in New South Wales, Australia completed semi-structured telephone interviews guided by the Car Technology Acceptance Model. All interviews were audio-recorded and transcribed verbatim. Content analysis and deductive-inductive thematic analysis were completed on each transcript independently by two researchers, with all themes presented to the investigative team, discussed until consensus was reached. Participant recruitment were ceased after thematic saturation. Results: 24 participants (mean age: 74.5 years; 13 males, 11 females) were interviewed. Eleven different AVTs were mentioned by participants. Attitudes towards these AVTs impacted how much participants understood how these technologies worked. These attitudes and motivation of technology usage could be explained by four major themes; (1) AVTs help with safety but overall responsibility remains with the driver, (2) Lack of clear information and instructions make AVTs look confusing, (3) AVTs need to be more user-friendly for older adults, and (4) Expensive out-of-pocket costs stop AVT usage. Conclusions: Despite understanding the safety benefits of simple, standard AVTs, older drivers perceive barriers that hinder their use of more complicated technologies. Increased consultations to make AVTs more acceptable to older adults are needed. In conjunction, more resources and options aimed at helping older adults better understand and access AVTs need to be developed

Welding of High Entropy Alloys A Review

High-entropy alloy (HEA) offers great flexibility in materials design with 3–5 principal elements and a range of unique advantages such as good microstructure stability, mechanical strength over a broad range of temperatures and corrosion resistance, etc. Welding of high entropy alloy, as a key joining method, is an important emerging area with significant potential impact to future application-oriented research and technological developments in HEAs. The selection of feasible welding processes with optimized parameters is essential to enhance the applications of HEAs. However, the structure of the welded joints varies with material systems, welding methods and parameters. A systemic understanding of the structures and properties of the weldment is directly relevant to the application of HEAs as well as managing the effect of welding on situations such as corrosion that are known to be a service life limiting factor of welded structures in conditions such as marine environments. In this paper, key recent work on welding of HEAs is reviewed in detail focusing on the research of main HEA systems when applying different welding techniques. The experimental details including sample preparation, sample size (thickness) and welding conditions reflecting energy input are summarized and key issues are highlighted. The microstructures and properties of different welding zones, in particular the fusion zone (FZ) and the heat affected zones (HAZ), formed with different welding methods are compared and presented in details and the structure-property relationships are discussed. The work shows that the weldability of HEAs varies with the HEA composition groups and the welding method employed. Arc and laser welding of AlCoCrFeNi HEAs results in lower hardness in the FZ and HAZ and reduced overall strength. Friction stir welding results in higher hardness in the FZ and achieves comparable/higher strength of the welded joints in tensile tests. The welded HEAs are capable of maintaining a reasonable proportion of the ductility. The key structure changes including element distribution, the volume fraction of face centered cubic (FCC) and body centered cubic (BCC) phase as well as reported changes in the lattice constants are summarized and analyzed. Detailed mechanisms governing the mechanical properties including the grain size-property/hardness relationship in the form of Hall–Petch (H–P) effect for both bulk and welded structure of HEAs are compared. Finally, future challenges and main areas to research are highlighted

The role of SNP-loop diuretic interactions in hypertension across ethnic groups in HyperGEN

Blood pressure (BP) is significantly influenced by genetic factors; however, less than 3% of the BP variance has been accounted for by variants identified from genome-wide association studies (GWAS) of primarily European-descent cohorts. Other genetic influences, including gene-environment (GxE) interactions, may explain more of the unexplained variance in BP. African Americans (AA) have a higher prevalence and earlier age of onset of hypertension (HTN) as compared with European Americans (EA); responses to anti-hypertensive drugs vary across race groups. To examine potential interactions between the use of loop diuretics and HTN traits, we analyzed systolic (SBP) and diastolic (DBP) blood BP from 1,222 AA and 1,231 EA participants in the Hypertension Genetic Epidemiology Network (HyperGEN). Population-specific score tests were used to test associations of SBP and DBP, using a panel of genotyped and imputed single nucleotide polymorphisms (SNPs) for African Americans (2.9 million SNPs) and European Americans (2.3 million SNPs). Several promising loci were identified through gene-loop diuretic interactions, although no SNP reached genome-wide significance after adjustment for genomic inflation. In AA, SNPs in or near the genes NUDT12, CHL1, GRIA1, CACNB2, and PYHIN1 were identified for SBP, and SNPs near ID3 were identified for DBP. For EA, promising SNPs for SBP were identified in ESR1and for DBP in SPATS2L and EYA2. Among these SNPs, none were common across phenotypes or population groups. Biologic plausibility exists for many of the identified genes, suggesting that these are candidate genes for regulation of BP and/or anti-hypertensive drug response. The lack of genome-wide significance is understandable in this small study employing gene-drug interactions. These findings provide a set of prioritized SNPs/candidate genes for future studies in HTN. Studies in more diversified population samples may help identify previously missed variants