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Search Results: 1 - 10 of 168244 matches for " Brian K. Lee "
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Weight Trimming and Propensity Score Weighting
Brian K. Lee,Justin Lessler,Elizabeth A. Stuart
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018174
Abstract: Propensity score weighting is sensitive to model misspecification and outlying weights that can unduly influence results. The authors investigated whether trimming large weights downward can improve the performance of propensity score weighting and whether the benefits of trimming differ by propensity score estimation method. In a simulation study, the authors examined the performance of weight trimming following logistic regression, classification and regression trees (CART), boosted CART, and random forests to estimate propensity score weights. Results indicate that although misspecified logistic regression propensity score models yield increased bias and standard errors, weight trimming following logistic regression can improve the accuracy and precision of final parameter estimates. In contrast, weight trimming did not improve the performance of boosted CART and random forests. The performance of boosted CART and random forests without weight trimming was similar to the best performance obtainable by weight trimmed logistic regression estimated propensity scores. While trimming may be used to optimize propensity score weights estimated using logistic regression, the optimal level of trimming is difficult to determine. These results indicate that although trimming can improve inferences in some settings, in order to consistently improve the performance of propensity score weighting, analysts should focus on the procedures leading to the generation of weights (i.e., proper specification of the propensity score model) rather than relying on ad-hoc methods such as weight trimming.
Non-invasive quantification of brain tumor-induced astrogliosis
Jisook Lee, Alexandra K Borboa, Andrew Baird, Brian P Eliceiri
BMC Neuroscience , 2011, DOI: 10.1186/1471-2202-12-9
Abstract: Using transgenic mice expressing firefly luciferase under the regulation of the GFAP promoter (GFAP-luc), we developed a model system to monitor astrogliosis upon tumor growth in a rapid, non-invasive manner. A biphasic induction of astrogliosis was observed in our xenograft model in which an early phase of activation of GFAP was associated with inflammatory response followed by a secondary, long-term upregulation of GFAP. These animals reveal GFAP activation with kinetics that is in parallel with tumor growth. Furthermore, a strong correlation between astrogliosis and tumor size was observed.Our results suggest that non-invasive, quantitative bioluminescent imaging using GFAP-luc reporter animal is a useful tool to monitor temporal-spatial kinetics of host-mediated astrogliosis that is associated with glioma and metastatic brain tumor growth.The tumor microenvironment is a dynamic niche for tissue remodeling because of its production of tumor cell- and host stromal cell-derived growth factors, cytokines and matrix proteins. Historically, the study of such host-stromal interactions has generally relied on classical histological methods such as immunohistochemistry, in situ hybridization or biochemical techniques such as immunoblotting and enzyme assays. Unfortunately, the analytical power of these techniques is limited by the ability of reagents to distinguish between tumor and host compartments and by the need for terminal harvest of tissues for analysis. For example, in malignant gliomas, tumor cells co-opt the functions of the surrounding brain to support their growth and invasion. However, gliomas fail to completely compromise an otherwise tight blood brain barrier of normal vessels, based on the wide range of drugs and small molecules that fail to cross the BBB and target brain tumors [1].GFAP expression has been widely used as a marker for astrogliosis and the host response to injury [2-4] and its analysis has generally relied on immunohistochemistry rather th
Total Blood Mercury Levels and Depression among Adults in the United States: National Health and Nutrition Examination Survey 2005–2008
Tsz Hin H. Ng, Jana M. Mossey, Brian K. Lee
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079339
Abstract: Background Mercury is a neurotoxicant linked with psychiatric symptoms at high levels of exposure. However, it is unclear whether an association is present at the low exposure levels in the US adult population. Materials and Methods Cross-sectional associations of total blood mercury and depression were assessed in 6,911 adults age ≥20 in the National Health and Nutrition Examination Survey (NHANES), 2005–2008. The Patient Health Questionnaire-9 was used to assess depression (high likelihood of a depressive spectrum disorder diagnosis; score 5–27). Results Unadjusted survey weighted logistic regression suggested that higher total blood mercury was associated with lower odds of depression (Odds Ratio = 0.49, 95% Confidence Interval: 0.36–0.65, comparing the highest and lowest mercury quintiles). This association largely disappeared after adjustment for sociodemographic variables (income-poverty ratio, education, marital status). However, in age-stratified analyses, this inverse relationship remained in older adults (age ≥40) even after adjustment for sociodemographic variables. Simulation analyses adjusting for expected confounding effects of fish intake suggested that the inverse relationship among older adults may be plausibly attributed to residual confounding (Odds Ratio = 0.75, 95% Confidence Interval: 0.50–1.12, comparing the highest and lowest mercury quintiles). Conclusions Higher total blood mercury was not associated with increased odds of depression. The lower odds of depression in older adults with higher total blood mercury may be due to residual confounding.
Geometric Structures on Spaces of Weighted Submanifolds
Brian Lee
Symmetry, Integrability and Geometry : Methods and Applications , 2009,
Abstract: In this paper we use a diffeo-geometric framework based on manifolds that are locally modeled on ''convenient'' vector spaces to study the geometry of some infinite dimensional spaces. Given a finite dimensional symplectic manifold (M,ω), we construct a weak symplectic structure on each leaf I_w of a foliation of the space of compact oriented isotropic submanifolds in M equipped with top degree forms of total measure 1. These forms are called weightings and such manifolds are said to be weighted. We show that this symplectic structure on the particular leaves consisting of weighted Lagrangian submanifolds is equivalent to a heuristic weak symplectic structure of Weinstein [Adv. Math. 82 (1990), 133-159]. When the weightings are positive, these symplectic spaces are symplectomorphic to reductions of a weak symplectic structure of Donaldson [Asian J. Math. 3 (1999), 1-15] on the space of embeddings of a fixed compact oriented manifold into M. When M is compact, by generalizing a moment map of Weinstein we construct a symplectomorphism of each leaf I_w consisting of positive weighted isotropic submanifolds onto a coadjoint orbit of the group of Hamiltonian symplectomorphisms of M equipped with the Kirillov-Kostant-Souriau symplectic structure. After defining notions of Poisson algebras and Poisson manifolds, we prove that each space I_w can also be identified with a symplectic leaf of a Poisson structure. Finally, we discuss a kinematic description of spaces of weighted submanifolds.
Geometric Structures on Spaces of Weighted Submanifolds
Brian Lee
Mathematics , 2009, DOI: 10.3842/SIGMA.2009.099
Abstract: In this paper we use a diffeo-geometric framework based on manifolds that are locally modeled on "convenient" vector spaces to study the geometry of some infinite dimensional spaces. Given a finite dimensional symplectic manifold $(M,\omega)$, we construct a weak symplectic structure on each leaf ${\textbf I}_{w}$ of a foliation of the space of compact oriented isotropic submanifolds in $M$ equipped with top degree forms of total measure 1. These forms are called weightings and such manifolds are said to be weighted. We show that this symplectic structure on the particular leaves consisting of weighted Lagrangian submanifolds is equivalent to a heuristic weak symplectic structure of Weinstein [Adv. Math. 82 (1990), 133-159]. When the weightings are positive, these symplectic spaces are symplectomorphic to reductions of a weak symplectic structure of Donaldson [Asian J. Math. 3 (1999), 1-15] on the space of embeddings of a fixed compact oriented manifold into $M$. When $M$ is compact, by generalizing a moment map of Weinstein we construct a symplectomorphism of each leaf ${\textbf I}_{w}$ consisting of positive weighted isotropic submanifolds onto a coadjoint orbit of the group of Hamiltonian symplectomorphisms of $M$ equipped with the Kirillov-Kostant-Souriau symplectic structure. After defining notions of Poisson algebras and Poisson manifolds, we prove that each space ${\textbf I}_{w}$ can also be identified with a symplectic leaf of a Poisson structure. Finally, we discuss a kinematic description of spaces of weighted submanifolds.
Constructing a Population-Based Research Database from Routine Maternal Screening Records: A Resource for Studying Alloimmunization in Pregnant Women
Brian K. Lee, Alexander Ploner, Zhongxing Zhang, Gunilla Gryfelt, Agneta Wikman, Marie Reilly
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027619
Abstract: Background Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues. Study Design and Methods Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies) presented as online moving graphical displays. Results More than one million (1,191,761) births with valid screening information from 1982–2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time. Conclusion This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important clinical questions, such as the etiological significance of non-anti-D antibodies.
Inhibition of CD4+CD25+ Regulatory T Cell Function and Conversion into Th1-Like Effectors by a Toll-Like Receptor-Activated Dendritic Cell Vaccine
Major K. Lee, Shuwen Xu, Elizabeth H. Fitzpatrick, Anupama Sharma, Holly L. Graves, Brian J. Czerniecki
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074698
Abstract: Despite the success of vaccines against some microbial pathogens, their utility in the prevention and treatment of cancer has thus far been limited. We have previously demonstrated that vaccination with dendritic cells activated with the TLR-4 ligand LPS and IFN-γ promotes an antigen-specific anti-tumor response that prevents tumor recurrence. To evaluate this mechanistically, we here studied the effects of this TLR-activated DC on regulatory T cell activity. Dendritic cells activated with LPS and IFN- γ negated the effects of regulatory T cells on responder cell proliferation. Restoration of responder cell proliferation was noted when TLR-activated dendritic cells were separated from both regulators and responders by a semi-permeable membrane. The effect is therefore mediated by a soluble factor but was independent of both IL-6 and IL-12. Furthermore, the soluble mediator appeared to act at least in part on the regulators themselves rather than responder cells exclusively. Because recent studies have demonstrated conversion of T regulatory cells into IL-17-producing effectors, we further questioned whether the TLR-activated dendritic cell would induce cytokine production and effector function in our system. We found that regulators produced a substantial amount of IFN- γ in the presence of TLR-activated dendritic cells but not immature dendritic cells. IFN-γ production was associated with upregulation of the Th1 transcriptional regulator T-bet, and a significant fraction of IFN-γ-producing regulators coexpressed T-bet and FoxP3. While the effects of the LPS-activated dendritic cell on responder cell proliferation were IL-12 independent, upregulation of T-bet was inhibited by a neutralizing anti-IL-12 antibody. Collectively, these and prior data suggest that varying innate immune signals may direct the phenotype of the immune response in part by inhibiting suppressor T cells and promoting differentiation of these regulators into particular subsets of effectors.
Differentiation of Material Temperature through the Application of Increased Localized Dissolution via Heat Transfer  [PDF]
Brian K. Chen
Journal of Analytical Sciences, Methods and Instrumentation (JASMI) , 2015, DOI: 10.4236/jasmi.2015.53005
Abstract: Increased temperature of a solution increases its solubility, allowing for a greater level of dissolution of the solute. A greater level of dissolution will result in a change in the density of the solution. When a localized area of the solution is of a different temperature, this will affect the localized density. Density is one of the factors affecting rate of sinking and the difference in temperature will lead to a change in the rate of sinking. Thus, when an object is at different temperatures, it will transfer heat to or from the solution in different manners and the rate of sinking will be different. This study tested whether sinking rate in a solution with excess solute could be used to judge the temperature of an object and the effect was confirmed with impure Graphite blocks in a Potassium Iodide solution.
Autism Spectrum Disorders in the Stockholm Youth Cohort: Design, Prevalence and Validity
Selma Idring, Dheeraj Rai, Henrik Dal, Christina Dalman, Harald Sturm, Eric Zander, Brian K. Lee, Eva Serlachius, Cecilia Magnusson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041280
Abstract: Objective Reports of rising prevalence of autism spectrum disorders (ASD), along with their profound personal and societal burden, emphasize the need of methodologically sound studies to explore their causes and consequences. We here present the design of a large intergenerational resource for ASD research, along with population-based prevalence estimates of ASD and their diagnostic validity. Method The Stockholm Youth Cohort is a record-linkage study comprising all individuals aged 0–17 years, ever resident in Stockholm County in 2001–2007 (N = 589,114). ASD cases (N = 5,100) were identified using a multisource approach, involving registers covering all pathways to ASD diagnosis and care, and categorized according to co-morbid intellectual disability. Prospectively recorded information on potential determinants and consequences of ASD were retrieved from national and regional health and administrative registers. Case ascertainment was validated through case-note review, and cross validation with co-existing cases in a national twin study. Results The 2007 year prevalence of ASD in all children and young people was 11.5 per 1,000 (95% confidence interval 11.2–11.8), with a co-morbid intellectual disability recorded in 42.6% (41.0–44.2) of cases. We found 96.0% (92.0–98.4) of reviewed case-notes being consistent with a diagnosis of ASD, and confirmed ASD in 85.2% (66.2–95.8) of affected twins. Conclusions Findings from this contemporary study accords with recently reported prevalence estimates from Western countries at around 1%, based on valid case ascertainment. The Stockholm Youth Cohort, in light of the availability of extensive information from Sweden's registers, constitutes an important resource for ASD research. On-going work, including collection of biological samples, will enrich the study further.
Expression Analysis of Stress-Related Genes in Kernels of Different Maize (Zea mays L.) Inbred Lines with Different Resistance to Aflatoxin Contamination
Tingbo Jiang,Boru Zhou,Meng Luo,Hamed K. Abbas,Robert Kemerait,Robert Dewey Lee,Brian T. Scully,Baozhu Guo
Toxins , 2011, DOI: 10.3390/toxins3060538
Abstract: This research examined the expression patterns of 94 stress-related genes in seven maize inbred lines with differential expressions of resistance to aflatoxin contamination. The objective was to develop a set of genes/probes associated with resistance to A. flavus and/or aflatoxin contamination. Ninety four genes were selected from previous gene expression studies with abiotic stress to test the differential expression in maize lines, A638, B73, Lo964, Lo1016, Mo17, Mp313E, and Tex6, using real-time RT-PCR. Based on the relative-expression levels, the seven maize inbred lines clustered into two different groups. One group included B73, Lo1016 and Mo17, which had higher levels of aflatoxin contamination and lower levels of overall gene expression. The second group which included Tex6, Mp313E, Lo964 and A638 had lower levels of aflatoxin contamination and higher overall levels of gene expressions. A total of six “cross-talking” genes were identified between the two groups, which are highly expressed in the resistant Group 2 but down-regulated in susceptible Group 1. When further subjected to drought stress, Tex6 expressed more genes up-regulated and B73 has fewer genes up-regulated. The transcript patterns and interactions measured in these experiments indicate that the resistant mechanism is an interconnected process involving many gene products and transcriptional regulators, as well as various host interactions with environmental factors, particularly, drought and high temperature.
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