A Rapid Segmentation-Insensitive "Digital Biopsy" Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer.

Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required

Essays in Health Economics

Health is defined as an individual\u27s mental or physical condition and being healthy means to be free from illness or injury. Health is relevant to both the supply and demand sides of the national economy. On the demand side, consumers derive satisfaction from being healthy. Consumers purchase goods and services to improve their health but also engage in activities that impair health such as smoking or drinking too much. On the supply side, firms produce health care goods and services to meet the market demand for health care derived from consumers\u27 demand for better health. In addition, health augments labor inputs since the healthier the population, the larger the labor force and the higher the marginal productivity of labor, as in fewer sick days. This dissertation is comprised of three essays related to the effect of social environments and economic incentives on health and health behaviors. The first essay examines whether immigrants converge towards natives\u27 level of smoking prevalence with assimilation. Results show that assimilation is associated with a greater likelihood of being a smoker for immigrants from lower smoking countries relative to the U.S. and a lower likelihood of being smoker for immigrants from higher smoking countries. Differences in responsiveness to taxes or smoke free air laws cannot explain the convergence in smoking rates between immigrants from higher and lower smoking countries. The second essay examines the effect of mortgage debt on health. Homeownership in the U.S. is promoted through the use of financing. These policies improve the liquidity of the housing market and make homeownership more affordable. But it also encourages greater consumption of mortgage debt. Using mortgage loan to value (LTV) as a proxy for financial stress, I show that homeowners with high LTVs are more likely to be in poor health. The third essay examines the effect of unemployment duration on health. I hypothesis that unemployment duration affects health through financial stress. Results show that high mortgage loan to value is not significantly correlated with most measures of poor health but when interacted with high home leverage is positively and significantly correlated with poor health. However, I cannot rule out reverse causality given that those in poor health have a significant likelihood of having high LTV in the next period

Dynamical studies of macroscopic superposition states: Phase engineering of controlled entangled number states of Bose-Einstein condensate in multiple wells

We provide a scheme for the generation of entangled number states of Bose-Einstein condensates in multiple wells with cyclic pairwise connectivity. The condensate ground state in a multiple well trap can self-evolve, when phase engineered with specific initial phase differences between the neighboring wells, to a macroscopic superposition state with controllable entanglement -- to multiple well generalization of double well NOON states. We demonstrate through numerical simulations the creation of entangled states in three and four wells and then explore the creation of "larger" entangled states where there are either a larger number of particles in each well or a larger number of wells. The type of entanglement produced as the particle numbers, or interaction strength, increases changes in a novel and initially unexpected manner.Comment: 13 pages, 14 figure

Social, Cultural and Behavioral Determinants of Health among Hawaii Filipinos: The Filipino Healthy Communities Project

Background/Purpose: Filipinos are Hawaii’s largest immigrant group and second largest ethnic group. The Hawaii Filipino Health Communities Project was initiated by the Hawaii State Department of Health, because of the high rates of heart disease and stroke mortality, and other behavioral risks seen among Hawaii’s Filipino population (i.e. high smoking rates among Filipino men). The project sought to gather Filipino community members’ perspectives on why such chronic disease health disparities exist for Filipinos, and identify solutions to address them. Methods: The project gathered information from both immigrant and local Filipinos throughout the state, using community engagement methods of interviews with community leaders (n=20) and community-based focus groups (n=20 groups with 130 participants), Results: Filipino community members were aware of, and community leaders well-versed in, the behavioral, cultural, and social determinants of health in their communities. However, being aware of such determinants of health has yet not resulted in changed behavior in the overall Filipino community (i.e. improved diet, increased physical activity, or better access to healthcare). Conclusion: More outreach is needed with Filipinos, along with interventions to combat health disparities in chronic disease, such as increased smoking cessation and creative ways to eat healthier and increase physical activit

Octopamine Neuromodulatory Effects on a Social Behavior Decision-Making Network in Drosophila Males

Situations requiring rapid decision-making in response to dynamic environmental demands occur repeatedly in natural environments. Neuromodulation can offer important flexibility to the output of neural networks in coping with changing conditions, but the contribution of individual neuromodulatory neurons in social behavior networks remains relatively unknown. Here we manipulate the Drosophila octopaminergic system and assay changes in adult male decision-making in courtship and aggression paradigms. When the functional state of OA neural circuits is enhanced, males exhibit elevated courtship behavior towards other males in both behavioral contexts. Eliminating the expression of the male form of the neural sex determination factor, Fruitless (FruM), in three OA suboesophageal ganglia (SOG) neurons also leads to increased male-male courtship behavior in these same contexts. We analyzed the fine anatomical structure through confocal examination of labeled single neurons to determine the arborization patterns of each of the three FruM-positive OA SOG neurons. These neurons send processes that display mirror symmetric, widely distributed arbors of endings within brain regions including the ventrolateral protocerebra, the SOG and the peri-esophageal complex. The results suggest that a small subset of OA neurons have the potential to provide male selective modulation of behavior at a single neuron level

Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer

Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition

Sprouty2 loss‐induced IL6 drives castration‐resistant prostate cancer through scavenger receptor B1

Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal form of treatment‐resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre‐clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self‐sufficient form of CRPC. Mechanistically, HER2‐IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1‐mediated cholesterol uptake in SPRY2‐deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2‐deficient CRPC is dependent on cholesterol bioavailability and SRB1‐mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2‐deficient CRPC