MODELING, OPTIMIZING, AND BUILDING OF A CONTINUOUS-FLOW XENON-129 POLARIZER WITH LUNG AND BROWN ADIPOSE TISSUE MAGNETIC RESONANCE IMAGING APPLICATIONS

Applications of hyperpolarized 129Xe gas are quickly expanding from gas-phase lung ventilation imaging to dissolved-phase imaging in the lungs and in distal organs. The largest barrier to dissolved-phase imaging continues to be the low xenon polarization value that can be obtained with continuous-flow, spin exchange optical pumping (SEOP). While theoretically polarization values should approach 90%, in practice they have been around 30%. Research in our lab on the SEOP process occurring inside the optical pumping cell, using finite element analysis simulations, pointed out major shortcomings in the entire continuous flow SEOP setup. The goal of my work is to improve the SEOP setup. To this end, I have designed and constructed a new continuous flow 129Xe polarizer that is expected to increase xenon residency time inside the optical pumping cell and reduce turbulence. At the same time, the new polarizer will make use of a new narrow laser that is specifically designed to optimize the optical pumping process. One of the applications of gas-phase hyperpolarized 129Xe gas is lung ventilation imaging. Fluorine-19 gas imaging has been proposed as an easier alternative to lung ventilation imaging with hyperpolarized gases. Here we compare the ability of 19F to that of hyperpolarized 129Xe gas MRI to detect ventilation defects in cystic fibrosis patients. One of the applications of dissolved-phase hyperpolarized 129Xe is the detection and thermometry of brown adipose tissue. Brown adipose tissue is a metabolically active fat tissue whose malfunction has been recently associated with the development of obesity and diabetes. Fat fraction MR techniques have also been proposed as a high-resolution alternative method to detect and quantify brown adipose tissue. Here we analyze some of the shortcomings of these techniques, specifically the specificity of fat fraction to brown adipose tissue and the effect of microscopic magnetic susceptibility gradients on fat fraction quantification.Doctor of Philosoph

Bacterial assemblages of the eastern Atlantic Ocean reveal both vertical and latitudinal biogeographic signatures

Microbial communities are recognized as major drivers of the biogeochemical processes in the oceans. However, the genetic diversity and composition of those communities is poorly understood. The aim of this study is to investigate the composition of bacterial assemblages in three different water layer habitats: surface (2–20 m), deep chlorophyll maximum (DCM; 28–90 m), and deep (100–4600 m) at nine stations along the eastern Atlantic Ocean from 42.8° N to 23.7° S. The sampling of three discrete, predefined habitat types from different depths, Longhurstian provinces, and geographical locations allowed us to investigate whether marine bacterial assemblages show spatial variation and to determine if the observed spatial variation is influenced by current environmental conditions, historical/geographical contingencies, or both. The PCR amplicons of the V6 region of the 16S rRNA from 16 microbial assemblages were pyrosequenced, generating a total of 352 029 sequences; after quality filtering and processing, 257 260 sequences were clustered into 2871 normalized operational taxonomic units (OTU) using a definition of 97% sequence identity. Community ecology statistical analyses demonstrate that the eastern Atlantic Ocean bacterial assemblages are vertically stratified and associated with water layers characterized by unique environmental signals (e.g., temperature, salinity, and nutrients). Genetic compositions of bacterial assemblages from the same water layer are more similar to each other than to assemblages from different water layers. The observed clustering of samples by water layer allows us to conclude that contemporary environments are influencing the observed biogeographic patterns. Moreover, the implementation of a novel Bayesian inference approach that allows a more efficient and explicit use of all the OTU abundance data shows a distance effect suggesting the influence of historical contingencies on the composition of bacterial assemblages. Surface bacterial communities displayed a general congruency with the ecological provinces as defined by Longhurst with modest exceptions usually associated with unique hydrographic and biogeochemical features. Collectively, our findings suggest that vertical (habitat) and latitudinal (distance) biogeographic signatures are present and that both environmental parameters and ecological provinces drive the composition of bacterial assemblages in the eastern Atlantic Ocean

Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions

AbstractThe koala retrovirus (KoRV), which is transitioning from an exogenous to an endogenous form, has been associated with high mortality in koalas. For other retroviruses, the envelope protein p15E has been considered a candidate for vaccine development. We therefore examined proviral sequence variation of KoRV p15E in a captive Queensland and three wild southern Australian koalas. We generated 163 sequences with intact open reading frames, which grouped into 39 distinct haplotypes. Sixteen distinct haplotypes comprising 139 of the sequences (85%) coded for the same polypeptide. Among the remaining 23 haplotypes, 22 were detected only once among the sequences, and each had 1 or 2 non-synonymous differences from the majority sequence. Several analyses suggested that p15E was under purifying selection. Important epitopes and domains were highly conserved across the p15E sequences and in previously reported exogenous KoRVs. Overall, these results support the potential use of p15E for KoRV vaccine development

Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty

AbstractColchicine, an antimitogenic agent, has shown promise in preventing restenosis after coronary angioplasty in experimental animal models. A prospective trial was conducted involving 197 patients randomized in a 2:1 fashion to treatment with oral colchicine, 0.6 mg twice daily (130 patients), or placebo (67 patients) for 6 months after elective coronary angioplasty. Treatment in all patients began between 12 h before angioplasty and 24 h after angioplasty. Compliance monitoring revealed that 96% of all prescribed pills were ingested. Demographic characteristics were similar in colchicine- and placebo-treated groups. A mean of 2.7 lesions/patient were dilated. Side effects resulted in a 6.9% dropout rate in the colchicine-treated patients.Complete quantitative angiographic follow-up was obtained in 145 patients (74%) with 393 dilated lesions. Quantitative angiographic measurements were obtained in two orthogonal views at baseline before angioplasty and immediately and at 6 months after angioplasty. The quantitative mean lumen diameter stenosis before angioplasty was 67% both in the 152 lesions in the placebo-treated group and in the 241 lesions in the colchkine-treated group; this value was reduced to 24% immediately after angio-plasty in the lesions in both treatment groups.At the 6-month angiogram, lesions had restenosed to 47% lumen diameter narrowing in the placebo-treated group compared with 46% in the colchicine-treated group (p = NS). Forty-one percent of colchicine-treated patients developed restenosis in at least one lesion compared with 45% of the placebo-treated group (p = NS). In conclusion, colchicine was ineffective for preventing restenosis after coronary angioplasty

Effects of superparamagnetic iron oxide nanoparticles on the longitudinal and transverse relaxation of hyperpolarized xenon gas

SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) are often used in magnetic resonance imaging experiments to enhance Magnetic Resonance (MR) sensitivity and specificity. While the effect of SPIONs on the longitudinal and transverse relaxation time of 1H spins has been well characterized, their effect on highly diffusive spins, like those of hyperpolarized gases, has not. For spins diffusing in linear magnetic field gradients, the behavior of the magnetization is characterized by the relative size of three length scales: the diffusion length, the structural length, and the dephasing length. However, for spins diffusing in non-linear gradients, such as those generated by iron oxide nanoparticles, that is no longer the case, particularly if the diffusing spins experience the non-linearity of the gradient. To this end, 3D Monte Carlo simulations are used to simulate the signal decay and the resulting image contrast of hyperpolarized xenon gas near SPIONs. These simulations reveal that signal loss near SPIONs is dominated by transverse relaxation, with little contribution from T1 relaxation, while simulated image contrast and experiments show that diffusion provides no appreciable sensitivity enhancement to SPIONs

Direct detection of brown adipose tissue thermogenesis in UCP1−/− mice by hyperpolarized 129Xe MR thermometry

Brown adipose tissue (BAT) is a type of fat specialized in non-shivering thermogenesis. While non-shivering thermogenesis is mediated primarily by uncoupling protein 1 (UCP1), the development of the UCP1 knockout mouse has enabled the study of possible UCP1-independent non-shivering thermogenic mechanisms, whose existence has been shown so far only indirectly in white adipose tissue and still continues to be a matter of debate in BAT. In this study, by using magnetic resonance thermometry with hyperpolarized xenon, we produce the first direct evidence of UCP1-independent BAT thermogenesis in knockout mice. We found that, following adrenergic stimulation, the BAT temperature of knockout mice increases more and faster than rectal temperature. While with this study we cannot exclude or separate the physiological effect of norepinephrine on core body temperature, the fast increase of iBAT temperature seems to suggest the existence of a possible UCP1-independent thermogenic mechanism responsible for this temperature increase

What Do Program Directors Value in Personal Statements? A Qualitative Analysis

Background: All applicants to accredited training programs must write a personal statement as part of the application process. This may provoke anxiety on the part of the applicant and can result in an impersonal product that does not enhance his or her application. Little has been written about what program directors are seeking in personal statements. Objective: To gain a better understanding of how pulmonary and critical care fellowship program directors view and interpret these essays and to help applicants create more effective personal statements and make the writing process less stressful. Methods: We surveyed the membership of the Association of Pulmonary and Critical Care Medicine Program Directors in 2018. Quantitative data were collected regarding the importance of the personal statement in the candidate selection process. Qualitative data exploring the characteristics of personal statements, what the personal statement reveals about applicants, and advice for writing them were also collected. Comparative analysis was used for coding and analysis of qualitative data. Results: Surveys were completed by 114 out of 344 possible respondents (33%). More than half of the respondents believed that the personal statement is at least moderately important when deciding to offer an interview, and 40% believed it is at least moderately important when deciding rank order. A qualitative analysis revealed consistent themes: communication skills, provision of information not found elsewhere, applicant characteristics, and things to avoid. Conclusion: The respondents view the personal statement as moderately important in the application process. They value succinct, quality writing that reveals personal details not noted elsewhere. The information presented may help reduce anxiety associated with writing the personal statement and result in making the personal statement a more meaningful part of the application

Forest Protection and Permanence of Reduced Emissions

Tropical forests are essential for climate change mitigation. As awareness grows over the use of credits from reduced emissions from deforestation and forest degradation (REDD+) and other nature-based climate solutions within both voluntary and compliance carbon markets, key concerns about the long-term durability of the reductions, or their permanence, arise for countries, corporations, regulators and policy makers. The paper seeks to analyze an efficient means of distribution and application of different policy pathways to slow down and stop deforestation and explore the longevity of reductions via modeling. The impact of policies like REDD+ most likely will have a time limitation. At some point tropical nations will take more responsibility to protect forests. REDD+ should constitute an initial intervention that will help tropical nations shock to a zero-deforestation trajectory. To establish conditions of permanence, we conduct numerical analyses using a model based on a cellular automata algorithm that learns from historical deforestation patterns and other spatial features in the Brazilian state of Mato Grosso. The model simulates future deforestation, first applying policy to reduce deforestation and then relaxing the policy intervention. Our simulations show that policies that are successful in reducing deforestation and related emissions from business as usual may have long-term positive consequences on an avoided deforestation trajectory even after potential policy reversals. Some accumulated gains could be lost but sizable benefits will remain, assuring permanence of emissions reduction during the policy implementation and potentially even after policies are relaxed. Hence, permanence depends both on the probability of policy reversals and the risk of emissions rebounding. Our results are important for advancing the understanding around the unsettled debate on the permanence of avoided emissions. Further, this paper argues that as policies to prevent deforestation or reduce emissions otherwise are reversible, permanence should be understood and discussed in a probabilistic and time-dependent framework

Evaluation of the Effect of Hydrated Lime on the Scavenging of Feral Swine (\u3ci\u3eSus Scrofa\u3c/i\u3e) Carcasses and Implications for Managing Carcass-Based Transmission of African Swine Fever Virus

African swine fever (ASF) is a devastating hemorrhagic disease marked by extensive morbidity and mortality in infected swine. The recent global movement of African swine fever virus (ASFV) in domestic and wild swine (Sus scrofa) populations has initiated preparedness and response planning activities within many ASF-free countries. Within the US, feral swine are of utmost concern because they are susceptible to infection, are wide-spread, and are known to interact with domestic swine populations. African swine fever virus is particularly hardy and can remain viable in contaminated carcasses for weeks to months; therefore, carcass-based transmission plays an important role in the epidemiology of ASF. Proper disposal of ASF-infected carcasses has been demonstrated to be paramount to curbing an ASF outbreak in wild boar in Europe; preparedness efforts in the US anticipate carcass management being an essential component of control if an introduction were to occur. Due to environmental conditions, geographic features, or limited personnel, immediately removing every carcass from the landscape may not be viable. Hydrated lime converts to calcium carbonate, forming a sterile crust that may be used to minimize pathogen amplification. Any disturbance by scavenging animals to the sterile crust would nullify the effect of the hydrated lime; therefore, this pilot project aimed to evaluate the behavior of scavenging animals relative to hydrated lime-covered feral swine carcasses on the landscape. At two of the three study sites, hydrated limetreated carcasses were scavenged less frequently compared to the control carcasses. Additionally, the median time to scavenging was 1 d and 6 d for control versus hydrated lime-treated carcasses, respectively. While results of this study are preliminary, hydrated lime may be used to deter carcass disruption via scavenging in the event that the carcass cannot be immediately removed from the landscape