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Search Results: 1 - 10 of 204512 matches for " Lisa P. Jacobson "
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Assessing the effect of HAART on change in quality of life among HIV-infected women
Chenglong Liu, Kathleen Weber, Esther Robison, Zheng Hu, Lisa P Jacobson, Stephen J Gange
AIDS Research and Therapy , 2006, DOI: 10.1186/1742-6405-3-6
Abstract: To assess the effect of HAART on QOL by comparing HIV-infected women using HAART with HIV-infected women remaining HAART na?ve in the Women's Interagency HIV Study (WIHS), a multicenter prospective cohort study begun in 1994 in the US.A 1:1 matching with equivalent (≤ 0.1%) propensity scores for predicting HAART initiation was implemented and 458 pairs were obtained. HAART effects were assessed using pattern mixture models. The changes of nine QOL domain scores and one summary score derived from a shortened version of the MOS-HIV from initial values were used as study outcomes.The background covariates of the treatment groups were well-balanced after propensity score matching. The 916 matched subjects had a mean age of 38.5 years and 42% had a history of AIDS diagnosis. The participants contributed a total of 4,292 person visits with a median follow-up time of 4 years. In the bivariate analyses with only HAART use and time as covariates, HAART was associated with short-term improvements of 4 QOL domains: role functioning, social functioning, pain and perceived health index. After adjusting for demographic, socioeconomic, biological and clinical variables, HAART had small but significant short-term improvements on changes in summary QOL (mean change: 3.25; P = 0.02), role functioning (6.99; P < 0.01), social functioning (5.74; P < 0.01), cognitive functioning (3.59; P = 0.03), pain (6.73; P < 0.01), health perception (3.67; P = 0.03) and perceived health index (4.87; P < 0.01). These QOL scores typically remained stable or declined over additional follow-up and there was no indication that HAART modified these trends.Our study demonstrated significant short-term HAART effects on most QOL domains, but additional use of HAART did not modify long-term trends. These changes could be attributed to the direct effect of HAART and indirect HAART effect mediated through clinical changes.As an important measure of self-reported health and well-being, health-related quality of
Injection drug use and patterns of highly active antiretroviral therapy use: an analysis of ALIVE, WIHS, and MACS cohorts
John D Morris, Elizabeth T Golub, Shruti H Mehta, Lisa P Jacobson, Stephen J Gange
AIDS Research and Therapy , 2007, DOI: 10.1186/1742-6405-4-12
Abstract: Longitudinal data collected between 1996 and 2004 contributed from 2,266 participants (37% with a reported history of IDU) who reported initiating their first HAART regimen during follow-up were utilized. Separate proportional-hazards models were used to identify factors measured prior to HAART-initiation associated with the time to first HAART discontinuation and first switch of components of HAART among continuous HAART users.The use of PI- vs. NNRTI-based regimens among HAART users with and without any history of IDU was similar over follow-up. The median time to a first report of discontinuation of HAART was 1.1 years for individuals with a history of IDU but 2.5 years for those without a history of IDU and multivariate analyses confirmed overall that individuals with a history of IDU were at greater risk for HAART discontinuation (adj RH = 1.24, 95% CI: 1.03–1.48). However, when restricting to data contributed after 1999, there was no longer any significant increased risk (adj RH = 1.05, 95% CI: 0.81–1.36). After adjusting for pre-HAART health status and prior ARV exposure, individuals who were ethnic/racial minorities, reported an annual income < $10,000/year, and were not employed were at significantly greater risk for HAART discontinuation. The median time to a first change in HAART regimen was approximately 1.5 years after first HAART report and was not elevated among those with a history of IDU (adj RH = 1.09, 95% CI: 0.89–1.34).Our analyses demonstrate that injection drug use by itself does not appear to be an independent risk factor for HAART switching or discontinuation in more recent years. However, as continued HAART use is of paramount importance for long-term control of HIV infection, efforts to improve maintenance to therapy among disadvantaged and minority populations remain greatly needed.Highly active antiretroviral therapy (HAART) has been unequivocally associated with improved survival among individuals infected with human immunodeficiency vir
Fidelity of SNP Array Genotyping Using Epstein Barr Virus-Transformed B-Lymphocyte Cell Lines: Implications for Genome-Wide Association Studies
Joshua T. Herbeck, Geoffrey S. Gottlieb, Kim Wong, Roger Detels, John P. Phair, Charles R. Rinaldo, Lisa P. Jacobson, Joseph B. Margolick, James I. Mullins
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006915
Abstract: Background As availability of primary cells can be limited for genetic studies of human disease, lymphoblastoid cell lines (LCL) are common sources of genomic DNA. LCL are created in a transformation process that entails in vitro infection of human B-lymphocytes with the Epstein-Barr Virus (EBV). Methodology/Principal Findings To test for genotypic errors potentially induced by the Epstein-Barr Virus transformation process, we compared single nucleotide polymorphism (SNP) genotype calls in peripheral blood mononuclear cells (PBMC) and LCL from the same individuals. The average mismatch rate across 19 comparisons was 0.12% for SNPs with a population call rate of at least 95%, and 0.03% at SNPs with a call rate of at least 99%. Mismatch rates were not correlated across genotype subarrays run on all sample pairs. Conclusions/Significance Genotypic discrepancies found in PBMC and LCL pairs were not significantly different than control pairs, and were not correlated across subarrays. These results suggest that mismatch rates are minimal with stringent quality control, and that most genotypic discrepancies are due to technical artifacts rather than the EBV transformation process. Thus, LCL likely constitute a reliable DNA source for host genotype analysis.
Lack of Evidence for Changing Virulence of HIV-1 in North America
Joshua T. Herbeck, Geoffrey S. Gottlieb, Xiuhong Li, Zheng Hu, Roger Detels, John Phair, Charles Rinaldo, Lisa P. Jacobson, Joseph B. Margolick, James I. Mullins
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001525
Abstract: Background Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic. We tested the hypothesis of changing HIV-1 virulence by examining trends in prognostic clinical markers of disease progression from 1984 to 2005 among nearly 400 antiretroviral-na?ve participants in the United States Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV infection in men who have sex with men (MSM). Methodology/Principal Findings Because clinical AIDS endpoints could not be used (due to antiretroviral therapies and prophylaxis), three prognostic markers of disease progression were used as proxies for HIV-1 virulence: plasma viral RNA load and CD4+ T cell count at “set point” (between ~9 and ~15 months after seroconversion), and rate of CD4 cell decline within three years after seroconversion. We performed multivariate analyses of the association between these markers and seroconversion year, with covariates including MACS site, race/ethnic group, seroconversion age, and CCR5Δ32 status. No statistically significant association was found between year of seroconversion and “set point” plasma viral load (at ~9 months after seroconversion: slope = ?0.004 log10 copies/mL/year, p = 0.76; at ~15 months: slope = ?0.005 log10 copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at ~9 months: slope = ?0.112 cells/μL/year, p = 0.22; at ~15 months: slope = ?0.047 cells/μL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = ?0.010 cells/ul/yr2, p = 0.88). Conclusions/Significance The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.
KIR/HLA Pleiotropism: Protection against Both HIV and Opportunistic Infections
Ying Qi,Maureen P Martin,Xiaojiang Gao,Lisa Jacobson,James J Goedert,Susan Buchbinder,Gregory D Kirk,Stephen J O'Brien,John Trowsdale,Mary Carrington
PLOS Pathogens , 2006, DOI: 10.1371/journal.ppat.0020079
Abstract: The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS.
Factors Affecting Glomerular Filtration Rate, as Measured by Iohexol Disappearance, in Men with or at Risk for HIV Infection
Joseph B. Margolick, Lisa P. Jacobson, George J. Schwartz, Alison G. Abraham, Annie T. Darilay, Lawrence A. Kingsley, Mallory D. Witt, Frank J. Palella
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086311
Abstract: Objective Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD). Design Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(?)) men (n = 258) in the Multicenter AIDS Cohort Study. Methods iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR). Results Median iGFR was higher among HIV(+) than HIV(?) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(?) men; predictors of CKD were similar using iGFR and eGFR. Conclusions iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR.
Sleep Disordered Breathing, Fatigue, and Sleepiness in HIV-Infected and -Uninfected Men
Susheel P. Patil, Todd T. Brown, Lisa P. Jacobson, Joseph B. Margolick, Alison Laffan, Lisette Johnson-Hill, Rebecca Godfrey, Jacquett Johnson, Sandra Reynolds, Alan R. Schwartz, Philip L. Smith
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099258
Abstract: Study Objectives We investigated the association of HIV infection and highly active antiretroviral therapy (HAART) with sleep disordered breathing (SDB), fatigue, and sleepiness. Methods HIV-uninfected men (HIV?; n = 60), HIV-infected men using HAART (HIV+/HAART+; n = 58), and HIV-infected men not using HAART (HIV+/HAART?; n = 41) recruited from two sites of the Multicenter AIDS cohort study (MACS) underwent a nocturnal sleep study, anthropometric assessment, and questionnaires for fatigue and the Epworth Sleepiness Scale. The prevalence of SDB in HIV- men was compared to that in men matched from the Sleep Heart Health Study (SHHS). Results The prevalence of SDB was unexpectedly high in all groups: 86.7% for HIV?, 70.7% for HIV+/HAART+, and 73.2% for HIV+/HAART?, despite lower body-mass indices (BMI) in HIV+ groups. The higher prevalence in the HIV? men was significant in univariate analyses but not after adjustment for BMI and other variables. SDB was significantly more common in HIV? men in this study than those in SHHS, and was common in participants with BMIs <25 kg/m2. HIV+ men reported fatigue more frequently than HIV? men (25.5% vs. 6.7%; p = 0.003), but self-reported sleepiness did not differ among the three groups. Sleepiness, but not fatigue, was significantly associated with SDB. Conclusions SDB was highly prevalent in HIV? and HIV+ men, despite a normal or slightly elevated BMI. The high rate of SDB in men who have sex with men deserves further investigation. Sleepiness, but not fatigue, was related to the presence of SDB. Clinicians caring for HIV-infected patients should distinguish between fatigue and sleepiness when considering those at risk for SDB, especially in non-obese men.
化学进展 , 2013, DOI: 10.7536/PC130205
Abstract: 原发性肝癌一直是中国启东癌症死亡的首要原因,这一地区的110万居民中大约每年有800人死于原发性肝癌。流行病学研究已经强调了乙肝病毒感染和肝致癌物黄曲霉素的饮食暴露在启东和其他流行地区作为关键相互作用的风险决定因素的重要性。由于生物标志物的发展,使得在病例对照研究和其他群体研究中可以检测这些风险因素的流行程度。20世纪80年代曾经在启东进行了乙肝病毒疫苗接种试点,但直到本世纪初才在新生儿上普遍接种。尽管目前疫苗接种对癌症死亡率的影响微乎其微,但该项目旨在减缓这一地区未来几代人肝脏疾病包括肝癌的发展。减少对黄曲霉毒素暴露的策略也是必需的,尤其是对于那些已经感染乙肝病毒的人群。我们已经进行了一系列原理验证性的临床试验,包括使用药物、膳食补充剂和食物来改变不可避免的暴露后黄曲霉素的代谢及排出。使用黄曲霉素生物标志物作为中间指标,奥替普拉、叶绿素和西兰花豆芽饮料已被证明有效,突出了低成本化学预防途径在预防环境致癌中的作用。值得注意的是,最近对存档的血清样本的回顾性分析表明,启东的黄曲霉素暴露在过去的25年里下降了40倍,这可能是由从玉米到大米的主食变化带来的。因此,一级预防,伴随着20世纪80年代经济和农业政策改变的作用,带来了出乎意料的在短时间内消除这个地区肝癌地方性流行的希望。
Binding-Site Assessment by Virtual Fragment Screening
Niu Huang,Matthew P. Jacobson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010109
Abstract: The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules) would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock ~11000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors.
Spinning Black Holes as Particle Accelerators
Ted Jacobson,Thomas P. Sotiriou
Physics , 2009, DOI: 10.1103/PhysRevLett.104.021101
Abstract: It has recently been pointed out that particles falling freely from rest at infinity outside a Kerr black hole can in principle collide with arbitrarily high center of mass energy in the limiting case of maximal black hole spin. Here we aim to elucidate the mechanism for this fascinating result, and to point out its practical limitations, which imply that ultra-energetic collisions cannot occur near black holes in nature.
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