Developments in 2D NMR relaxometry and its application to biological tissue

Abstract In this thesis the capability of 2D NMR relaxometry to distinguish between different biological tissues is established using fresh unpreserved samples of lamb’s liver and kidney. A novel use of 2D T1-T2 relaxation spectra to provide characteristic profiles of specific tissues in specific states of health is proposed and tested in the case of osteoarthritis using human articular knee cartilage obtained from the Norfolk and Norwich University Hospital (NNUH). It is then proposed that 2D relaxation spectra can be used to optimise image contrast, which is an outstanding problem in clinical MRI. Indeed clinical MRI lacks well established and accurate methods for optimising image contrast and fails to exploit much of the potential available to the NMR practitioner. In this thesis two methods for the optimisation of image contrast using 2D T1-T2 relaxation spectra are proposed and tested. These are named the Virtual Sample Simulation (VSS) and MRI COntrast Modelling (MRICOM) methods. It is shown that MRICOM is more generally applicable because it exploits the established Object-oriented Development Interface for NMR (ODIN). It is demonstrated that ‘in-silico’ methods can predict image intensity of specific tissues using specific imaging sequences and use them to optimise contrast between tissues. A newly developed single shot T1-T2 sequence named the ‘TR method’ is proposed and implemented in order to increase the speed of 2D NMR relaxometry by between 2 and 10 times. Its ability to distinguish between different biological tissues is established, again using fresh unpreserved samples of lamb’s liver and kidney. Future work is then proposed to combine this faster method with other time reduction methods and volume selective techniques to create the CURE (Clinical Ultrafast RElaxometry) protocol. Methods are also proposed to increase the tissue characterisation and diagnostic capabilities of 2D NMR relaxometry with the use of expert systems and neural networks

Physician Burnout in a Rural Kansas Community

Introduction Physician wellness and burnout are topics of intensediscussion and study, however, less is known about rural physicianburnout. The aim of this study was to assess levels of physicianburnout in the rural Kansas community of Salina. Methods An electronic, confidential survey was conducted among145 physicians with active privileges at the local health center and/orsurgical center. The survey included demographic features, practicecharacteristics, and the abbreviated Maslach Burnout Inventory™(aMBI). In addition, survey participants were invited to provide freetextresponses to questions concerning specific causes of burnoutand mechanisms to combat feelings of burnout. Results Of 145 invited, 76 physicians completed the survey. Thirty-six respondents self-identified as primary care physicians, 22as subspecialists, and 18 as surgeons. aMBI scores for emotionalexhaustion (EE), depersonalization (D) and personal accomplishment(PA) ranged from 0 to 18. The mean EE score was 8.4 (SD =4.9), mean D score was 4.8 (SD = 3.9), and mean PA score was 15.2(SD = 2.8). Using tertiles, physician burnout (i.e., those in the firsttertile) for EE was 39% (30/76), D was 34% (26/76), and PA was41% (31/75); 22% of physicians surveyed scored high on both EEand D as measured by tertiles, suggestive of more serious burnout.No significant differences in aMBI scores were observed for demographicfeatures or practice characteristics; physicians who workedwith medical students had higher PA scores. Contributing to burnoutwere demands of documentation and difficult patient encounters,while true time away might ameliorate rural physician burnout. Conclusions As measured by aMBI constructs, burnout is prevalentamong the responding rural physicians practicing in the Salina community

Post-Capillary Pulmonary Hypertension: Clinical Review

Pulmonary hypertension (PH) caused by left heart disease, also known as post-capillary PH, is the most common etiology of PH. Left heart disease due to systolic dysfunction or heart failure with preserved ejection fraction, valvular heart disease, and left atrial myopathy due to atrial fibrillation are causes of post-capillary PH. Elevated left-sided filling pressures cause pulmonary venous congestion due to backward transmission of pressures and post-capillary PH. In advanced left-sided heart disease or valvular heart disease, chronic uncontrolled venous congestion may lead to remodeling of the pulmonary arterial system, causing combined pre-capillary and post-capillary PH. The hemodynamic definition of post-capillary PH includes a mean pulmonary arterial pressure \u3e 20 mmHg, pulmonary vascular resistance \u3c 3 Wood units, and pulmonary capillary wedge pressure \u3e 15 mmHg. Echocardiography is important in the identification and management of the underlying cause of post-capillary PH. Management of post-capillary PH is focused on the treatment of the underlying condition. Strategies are geared towards pharmacotherapy and guideline-directed medical therapy for heart failure, surgical or percutaneous management of valvular disorders, and control of modifiable risk factors and comorbid conditions. Referral to centers with advanced heart and pulmonary teams has shown to improve morbidity and mortality. There is emerging interest in the use of targeted agents classically used in pulmonary arterial hypertension, but current data remain limited and conflicting. This review aims to serve as a comprehensive summary of postcapillary PH and its etiologies, pathophysiology, diagnosis, and management, particularly as it pertains to advanced heart failure

Nontemplated approach to tuning the spectral properties of cyanine-based fluorescent NanoGUMBOS

Template-free controlled aggregation and spectral properties in fluorescent organic nanoparticles (FONs) is highly desirable for various applications. Herein, we report a nontemplated method for controlling the aggregation in near-infrared (NIR) cyanine-based nanoparticles derived from a group of uniform materials based on organic salts (GUMBOS). Cationic heptamethine cyanine dye 1,1′,3,3,3′,3′-hexamethylindotricarbocyanine (HMT) was coupled with five different anions, viz., [NTf2-], [BETI -], [TFPB-], [AOT-], and [TFP4B-], by an ion-exchange method to obtain the respective GUMBOS. The nanoGUMBOS obtained via a reprecipitation method were primarily amorphous and spherical (30-100 nm) as suggested by selected area electron diffraction (SAED) and transmission electron microscopy (TEM). The formation of tunable self-assemblies within the nanoGUMBOS was characterized using absorption and fluorescence spectroscopy in conjunction with molecular dynamics simulations. Counterion-controlled spectral properties observed in the nanoGUMBOS were attributed to variations in J/H ratios with different anions. Association with the [AOT-] anion afforded predominant J aggregation enabling the highest fluorescence intensity, whereas [TFP4B-] disabled the fluorescence due to predominant H aggregation in the nanoparticles. Analyses of the stacking angle of the cations based on molecular dynamic simulation results in [HMT][NTf2], [HMT][BETI], and [HMT][AOT] dispersed in water and a visual analysis of the representative simulation snapshots also imply that the type of aggregation was controlled through the counterion associated with the dye cation. © 2010 American Chemical Society

Two contemporaneous mitogenomes from terminal Pleistocene burials in eastern Beringia

Pleistocene residential sites with multiple contemporaneous human burials are extremely rare in the Americas. We report mitochondrial genomic variation in the first multiple mitochondrial genomes from a single prehistoric population: two infant burials (USR1 and USR2) from a common interment at the Upward Sun River Site in central Alaska dating to ~11,500 calendar years before present (cal B.P.). Using a targeted capture method and next-generation sequencing we determined that the USR1 infant possessed variants that define mitochondrial lineage C1b, while the USR2 genome falls at the root of lineage B2, allowing us to refine younger coalescence age estimates for these two clades. C1b and B2 are rare to absent in modern populations of Northern North America. Documentation of these lineages at this location in the Late Pleistocene provides evidence for the extent of mitochondrial diversity in early Beringian populations, which supports the expectations of the Beringian Standstill Model

Developing Maintenance Cultures in UN Police Peacekeeping Operations

This report provides an analysis and evaluation of maintenance cultures in United Nations Police Contributing Countries (PCC) receiving funding for Formed Police Units from the United States. The US Department of State, Bureau of International Narcotics and Law Enforcement Affairs (INL) recognized a marked lack of research on maintenance cultures in police agencies receiving foreign funding and sought to build a base of knowledge to aid in creating and sustaining maintenance cultures within these organizations. The INL also requested analysis and evaluation of maintenance cultures in five specific African PCCs (Cameroon, Ghana, Rwanda, Senegal, and Togo), as well as recommendations to create and sustain maintenance cultures specific to these countries. By establishing effective maintenance cultures, INL seeks to ensure that equipment purchased with funding from the United States will operate effectively throughout the manufacturer's estimated life-span

Senior Recital

List of performers and performances

Prenatal exposure to maternal social disadvantage and psychosocial stress and neonatal white matter connectivity at birth

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. Mean diffusivity (MD) and fractional anisotropy (FA) were measured for the dorsal and inferior cingulum bundle (CB), uncinate, and fornix using probabilistic tractography in FSL. Social disadvantage and psychosocial stress were fitted to dMRI parameters using regression models adjusted for infant postmenstrual age at scan and sex. Social disadvantage, but not psychosocial stress, was independently associated with lower MD in the bilateral inferior CB and left uncinate, right fornix, and lower MD and higher FA in the right dorsal CB. Results persisted after accounting for maternal medical morbidities and prenatal drug exposure. In moderation analysis, psychosocial stress was associated with lower MD in the left inferior CB among the lower-to-higher socioeconomic status (SES) (INR ≥ 200%) group, but not the extremely low SES (INR \u3c 200%) group. Increasing access to social welfare programs that reduce the burden of social disadvantage and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways