Browsing by Author "Chen, Xi"
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Item Open Access Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography.(Ophthalmology, 2019-12) Hsu, S Tammy; Ngo, Hoan T; Stinnett, Sandra S; Cheung, Nathan L; House, Robert J; Kelly, Michael P; Chen, Xi; Enyedi, Laura B; Prakalapakorn, S Grace; Materin, Miguel A; El-Dairi, Mays A; Jaffe, Glenn J; Freedman, Sharon F; Toth, Cynthia A; Vajzovic, LejlaPURPOSE:To assess macular vasculature in healthy infants and children using OCT angiography (OCTA). DESIGN:Prospective cross-sectional study. PARTICIPANTS:One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center. METHODS:We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes. MAIN OUTCOME MEASURES:The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC. RESULTS:The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm2; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00). CONCLUSIONS:Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes.Item Open Access Bayesian Dynamic Modeling for Streaming Network Data(2017) Chen, XiStreaming network data of various forms arises in many applications, raising interest in research to model and quantify the nature of stochasticity and structure in dynamics underlying such data. One example context is that of traffic flow count data in networks, such as in automobile or aviation transportation, certain directed social network contexts, and Internet studies. Using an example of Internet browser traffic flows through site-segments of an international news website, I present Bayesian analyses of two new, linked classes of models which, in tandem, allow fast, scalable and interpretable Bayesian inference on dynamic patterns over time underlying flows. I develop two kinds of flexible state-space models for streaming count data, able to adaptively characterize and quantify network dynamics efficiently in real-time. These models are then used as emulators of more structured, time-varying gravity models that allow formal dissection of network dynamics. This yields interpretable inferences on traffic flow characteristics, and on dynamics in interactions among network nodes. Bayesian monitoring theory defines a strategy for sequential model assessment and adaptation in cases when network flow data deviates from model-based predictions. Exploratory and sequential monitoring analyses of evolving traffic on a network of web site-segments in e-commerce demonstrate the utility of this coupled Bayesian emulation approach to analysis of streaming network count data.
A second, different dynamic network context is that involving relational data. Examples include contexts of binary network data indicating communications or relationships between pairs of network nodes over time. Some popular examples include friendships over social networks and communications between different functional zones in brain. Using an example of co-movements of company stock indices, I develop and compare two different approaches. One involves latent threshold models mapping latent processes to binary entries via a probabilistic link function, a second involves dynamic generalized linear models for binary outcomes. Analyses implement using Markov chain Monte Carlo methods are available for these models, but naturally computationally demanding and not scalable to relevant network dimensions for many contexts. In contrast, dynamic generalized linear models can implemented using fast, effective approximate Bayesian computations for both sequential and retrospective analyses to enable linear-time computations. I also demonstrate the use of a model decoupling/recoupling strategy to enable scaling in network size.
Item Open Access Exploiting Common Structures Across Multiple Network Propagation Schemes(2018) Chen, XiPageRank is arguably the most popular graph-node ranking algorithm which has been used to analyze large networks.
This paper presents how to utilize common structures across multiple damping schemes in PageRank algorithm and its variants to improve computation efficiency. One contribution we have made is to make use of Krylov subspaces to fast approximate PageRank of the same graph, same personalized distribution vector across different damping factors. In the first run we compute an invariant subspace, which is the major time cost of our algorithm. The original network connection matrix is represented in the invariant subspace by a small matrix.
Afterward, for each different damping factor only the small matrix is involved, followed by a single matrix-vector multiplication. Another contribution is to re-index graph nodes, based on graph spectral method to improve data locality, and accelerate sparse matrix-vector multiplication. We applied the new method to large real-world network graphs and make comparisons between existing iterative methods and our method. Our algorithm has substantial lower cost in amortized time when multiple damping factors are used for network analysis.
Item Open Access H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.(PloS one, 2011-01) Moody, M Anthony; Zhang, Ruijun; Walter, Emmanuel B; Woods, Christopher W; Ginsburg, Geoffrey S; McClain, Micah T; Denny, Thomas N; Chen, Xi; Munshaw, Supriya; Marshall, Dawn J; Whitesides, John F; Drinker, Mark S; Amos, Joshua D; Gurley, Thaddeus C; Eudailey, Joshua A; Foulger, Andrew; DeRosa, Katherine R; Parks, Robert; Meyerhoff, R Ryan; Yu, Jae-Sung; Kozink, Daniel M; Barefoot, Brice E; Ramsburg, Elizabeth A; Khurana, Surender; Golding, Hana; Vandergrift, Nathan A; Alam, S Munir; Tomaras, Georgia D; Kepler, Thomas B; Kelsoe, Garnett; Liao, Hua-Xin; Haynes, Barton FDuring the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.Item Open Access How and to what extent can pensions facilitate increased use of health services by older people: evidence from social pension expansion in rural China.(BMC health services research, 2020-11) Chen, Shanquan; Chen, Xi; Law, Stephen; Lucas, Henry; Tang, Shenlan; Long, Qian; Xue, Lei; Wang, ZhengBackground
The proportion of people aged 60 years or over is growing faster than other age groups. Traditionally, retirement has been considered as both a loss to the labour market and an additional economic burden on the nation. More recently, it is widely accepted that retired people can still contribute to society in many ways, though the extent of their contributions will depend heavily on their state of health. In this context, a significant practical issue is how to encourage older people to use the health services they need. This study aims to evaluate the effects of pensions on older adults' health service utilization, and estimate the level of pension required to influence such utilization.Methods
Using data from a nationally representative sample survey, the China Health and Retirement Longitudinal Study, we adopted a fuzzy regression discontinuity design and undertook segmented regression analysis.Results
It was found that a pension did encourage low-income people to use both outpatient (OR = 1.219, 95% 1.018-1.460) and inpatient services (OR = 1.269, 95% 1.020-1.579); but also encouraged both low- and high-income people to choose self-treatment, specifically over-the-counter (OR = 1.208, 95% 1.037-1.407; OR = 1.206, 95% 1.024-1.419; respectively) and traditional Chinese medicines (OR = 1.452, 95% 1.094-1.932; OR = 1.456, 95% 1.079-1.955; respectively). However, receiving a pension had no effect on the frequency of outpatient and inpatient service use. Breakpoints for a pension to promote health service utilization were mainly located in the range 55-95 CNY (7.1-12.3 EUR or 8.0-13.8 USD).Conclusions
A pension was found to have mixed effects on health service utilization for different income groups. Our study enriches existing evidence on the impact of pensions on healthcare-seeking behaviour and can be helpful in policy design and the formulation of improved models relating to pensions and healthcare utilisation.Item Open Access IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.(PLoS One, 2014) Hwang, Kwan-Ki; Trama, Ashley M; Kozink, Daniel M; Chen, Xi; Wiehe, Kevin; Cooper, Abby J; Xia, Shi-Mao; Wang, Minyue; Marshall, Dawn J; Whitesides, John; Alam, Munir; Tomaras, Georgia D; Allen, Steven L; Rai, Kanti R; McKeating, Jane; Catera, Rosa; Yan, Xiao-Jie; Chu, Charles C; Kelsoe, Garnett; Liao, Hua-Xin; Chiorazzi, Nicholas; Haynes, Barton FB-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG1 antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and intestinal commensal bacteria. These IGHV1-69 B-CLL antibodies preferentially used IGHD3 and IGHJ6 gene segments and had long heavy chain complementary determining region 3s (HCDR3s) (≥21 aa). IGHV1-69 B-CLL BCRs exhibited a phenylalanine at position 54 (F54) of the HCDR2 as do rare HIV-1 gp41 and influenza hemagglutinin stem neutralizing antibodies, while IGHV1-69 gp41 antibodies induced by HIV-1 infection predominantly used leucine (L54) allelic variants. These results demonstrate that the B-CLL cell population is an expansion of members of the innate polyreactive B cell repertoire with reactivity to a number of infectious agent antigens including intestinal commensal bacteria. The B-CLL IGHV1-69 B cell usage of F54 allelic variants strongly suggests that IGHV1-69 B-CLL gp41 antibodies derive from a restricted B cell pool that also produces rare HIV-1 gp41 and influenza hemagglutinin stem antibodies.Item Open Access Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.(J Exp Med, 2011-10-24) Liao, Hua-Xin; Chen, Xi; Munshaw, Supriya; Zhang, Ruijun; Marshall, Dawn J; Vandergrift, Nathan; Whitesides, John F; Lu, Xiaozhi; Yu, Jae-Sung; Hwang, Kwan-Ki; Gao, Feng; Markowitz, Martin; Heath, Sonya L; Bar, Katharine J; Goepfert, Paul A; Montefiori, David C; Shaw, George C; Alam, S Munir; Margolis, David M; Denny, Thomas N; Boyd, Scott D; Marshal, Eleanor; Egholm, Michael; Simen, Birgitte B; Hanczaruk, Bozena; Fire, Andrew Z; Voss, Gerald; Kelsoe, Garnett; Tomaras, Georgia D; Moody, M Anthony; Kepler, Thomas B; Haynes, Barton FThe initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.Item Open Access Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.(J Virol, 2012-04) Bonsignori, Mattia; Montefiori, David C; Wu, Xueling; Chen, Xi; Hwang, Kwan-Ki; Tsao, Chun-Yen; Kozink, Daniel M; Parks, Robert J; Tomaras, Georgia D; Crump, John A; Kapiga, Saidi H; Sam, Noel E; Kwong, Peter D; Kepler, Thomas B; Liao, Hua-Xin; Mascola, John R; Haynes, Barton FPlasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities.