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Find video protocols related to scientific articles indexed in Pubmed.
Bayesian modeling and prediction of accrual in multi-regional clinical trials.
Stat Methods Med Res
PUBLISHED: 11-05-2014
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In multi-regional trials, the underlying overall and region-specific accrual rates often do not hold constant over time and different regions could have different start-up times, which combined with initial jump in accrual within each region often leads to a discontinuous overall accrual rate, and these issues associated with multi-regional trials have not been adequately investigated. In this paper, we clarify the implication of the multi-regional nature on modeling and prediction of accrual in clinical trials and investigate a Bayesian approach for accrual modeling and prediction, which models region-specific accrual using a nonhomogeneous Poisson process and allows the underlying Poisson rate in each region to vary over time. The proposed approach can accommodate staggered start-up times and different initial accrual rates across regions/centers. Our numerical studies show that the proposed method improves accuracy and precision of accrual prediction compared to existing methods including the nonhomogeneous Poisson process model that does not model region-specific accrual.
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[Distribution of copper and zinc in blood among general population from 8 provinces in China].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 04-22-2014
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To investigate the level of zinc (Zn) and copper (Cu) in whole blood among general population from 8 provinces in China, and to analyze the characteristics of distribution among different regions.
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[Polycyclic aromatic hydrocarbons monohydroxy metabolites level in urine of general population in eight provinces of China].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 04-22-2014
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To assess the levels of polycyclic aromatic hydrocarbons monohydroxy metabolites in urine of general population in China among 8 provinces, provide the baseline of the metabolites in the general population.
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[Study of distribution and influencing factors of arsenic in whole blood and urine among population in 8 provinces in China].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 04-22-2014
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To evaluated the levels of arsenic (As) in blood and urine among general population in China and analyze its influencing factors.
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[Study of distribution and influencing factors of lead and cadmium in whole blood and urine among population in 8 provinces in China].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 04-22-2014
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To evaluate the levels of lead (Pb) and cadmium (Cd) in blood and urine among general population in China, and thereby analyze their prevalent features.
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Identification and characterization of buffalo 7SK and U6 pol III promoters and application for expression of short hairpin RNAs.
Int J Mol Sci
PUBLISHED: 01-17-2014
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RNA polymerase III (pol III) type 3 promoters, such as 7SK and U6, are routinely used to induce short hairpin RNAs (shRNAs) to knockdown gene expression by RNA interference (RNAi). To extend the application of RNAi to studies of buffalo, an shRNAs expressing system using the buffalo pol III promoters was developed. Buffalo 7SK promoter (bu7SK) and U6 promoter (buU6) sequences upstream of the full-length 7SK and U6 small nuclear RNA sequence in the buffalo genome were identified and characterized, respectively. To determine the functionality of these promoters in constructs driving shRNA expression, anti-EGFP shRNAs (shEGFP) cassettes under the direction of bu7SK and buU6 were constructed. We further compared the EGFP knockdown efficiency of constructs using bu7SK and buU6 with that of promoters of human and bovine origins in BFF cells and mouse PT67 cells by flow cytometry and quantitative real-time PCR assays. We found that the bu7SK and buU6 promoters induced the greatest level of suppression in homologous and heterologous cells relative to promoters derived from other species. Taken together, functional bu7SK and buU6 promoters were identified and characterized, thus laying the groundwork for future development of RNAi therapeutics and gene modification in buffalo species.
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A Novel PCR-Based Approach to Discover miRNA Target Genes.
Int J Med Sci
PUBLISHED: 01-01-2014
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MiRNAs are potent regulators of gene expression, and most miRNAs have from several to several thousands of gene targets. Validating the numerous gene targets of a given miRNA remains challenging despite the existence of various tools and databases that predict candidate gene-miRNA pairs. In the present study, we present a high-throughput but flexible method that applies a PCR-based application to simulate the binding of miRNAs to their gene targets. Using hsa-miR-377 as an illustrative example, our method was able to identify 13 potential targets of hsa-miR-377. Moreover, our results include 2 genes (SOD2 and PPM1A) that have already been verified as targets of hsa-miR-377. Our method may provide an alternative way of identifying the gene targets of miRNAs for future research.
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[Evaluation of the cellulase cost during the cassava cellulose ethanol fermentation process].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 06-25-2013
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Cellulose takes nearly 10% (W/W) dry weight of cassava tubers. In this study, the cellulase cost of different ethanol fermentation from cassava cellulose was evaluated. The processes include the direct saccharification and fermentation of original cassava cellulose residues, the direct saccharification and fermentation of pretreated cassava cellulose residues, and the simultaneous co-saccharification and fermentation of cassava starch and cassava cellulose. The results show that the cassava cellulose utilization in the first two processes were low with the enzyme cost of 13 602 and 11 659 RMB Yuan per tone of ethanol, respectively. In the third process, the final ethanol concentration increased from 101.5 g/L to 107.0 g/L when cassava cellulose and cassava starch were saccharified simultaneously. Comparing to the first two processes, the third one demonstrated the lowest enzyme cost at 3 589 RMB Yuan per ton of ethanol, which was less than the ethanol price and no additional equipment and operation cost input were added. The conclusion provided a practical way of cassava cellulose utilization in cassava ethanol industry.
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Curcumin as a potential treatment for Alzheimers disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein.
Am. J. Chin. Med.
PUBLISHED: 01-23-2013
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Curcumin, an agent traditionally utilized for its preventative action against tumorigenesis, oxidation, inflammation, apoptosis and hyperlipemia, has also been used in the treatment of Alzheimers disease (AD). Recent advances in the study of AD have revealed astrocytes (AS) as being key factors in the early pathophysiological changes in AD. Glial fibrillary acidic protein (GFAP), a marker specific to AS, is markedly more manifest during morphological modifications and neural degeneration signature during the onset of AD. Several studies investigating the functionality of curcumin have shown that it not only inhibits amyloid sedimentation but also accelerates the disaggregation of amyloid plaque. Thus, we are interested in the relationship between curcumin and spatial memory in AD. In this study, we intend to investigate the effects of curcumin in amyloid-? (A?(1-40)) induced AD rat models on both the behavioral and molecular levels, that is to say, on their spatial memory and on the expression of GFAP in their hippocampi. Our results were statistically significant, showing that the spatial memory of AD rats improved following curcumin treatment (p < 0.05), and that the expression of GFAP mRNA and the number of GFAP positive cells in the curcumin treated rats was decreased relative to the AD group rats (p < 0.05). Furthermore, the expression level of GFAP mRNA in hippocampal AS in the AD rats significantly increased when compared with that in the sham control (p < 0.05). Taken together, these results suggest that curcumin improves the spatial memory disorders (such disorders being symptomatic of AD) in A?(1-40)-induced rats by down regulating GFAP expression and suppressing AS activity.
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Cost analysis of cassava cellulose utilization scenarios for ethanol production on flowsheet simulation platform.
Bioresour. Technol.
PUBLISHED: 01-06-2013
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Cassava cellulose accounts for one quarter of cassava residues and its utilization is important for improving the efficiency and profit in commercial scale cassava ethanol industry. In this study, three scenarios of cassava cellulose utilization for ethanol production were experimentally tested under same conditions and equipment. Based on the experimental results, a rigorous flowsheet simulation model was established on Aspen plus platform and the cost of cellulase enzyme and steam energy in the three cases was calculated. The results show that the simultaneous co-saccharification of cassava starch/cellulose and ethanol fermentation process (Co-SSF) provided a cost effective option of cassava cellulose utilization for ethanol production, while the utilization of cassava cellulose from cassava ethanol fermentation residues was not economically sound. Comparing to the current fuel ethanol selling price, the Co-SSF process may provide an important choice for enhancing cassava ethanol production efficiency and profit in commercial scale.
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Nonparametric multiple imputation for receiver operating characteristics analysis when some biomarker values are missing at random.
Stat Med
PUBLISHED: 10-26-2011
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The receiver operating characteristics (ROC) curve is a widely used tool for evaluating discriminative and diagnostic power of a biomarker. When the biomarker value is missing for some observations, the ROC analysis based solely on complete cases loses efficiency because of the reduced sample size, and more importantly, it is subject to potential bias. In this paper, we investigate nonparametric multiple imputation methods for ROC analysis when some biomarker values are missing at random and there are auxiliary variables that are fully observed and predictive of biomarker values and/or missingness of biomarker values. Although a direct application of standard nonparametric imputation is robust to model misspecification, its finite sample performance suffers from curse of dimensionality as the number of auxiliary variables increases. To address this problem, we propose new nonparametric imputation methods, which achieve dimension reduction through the use of one or two working models, namely, models for prediction and propensity scores. The proposed imputation methods provide a platform for a full range of ROC analysis and hence are more flexible than existing methods that primarily focus on estimating the area under the ROC curve. We conduct simulation studies to evaluate the finite sample performance of the proposed methods and find that the proposed methods are robust to various types of model misidentification and outperform the standard nonparametric approach even when the number of auxiliary variables is moderate. We further illustrate the proposed methods by using an observational study of maternal depression during pregnancy.
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Novel PEG-graft-PLA nanoparticles with the potential for encapsulation and controlled release of hydrophobic and hydrophilic medications in aqueous medium.
Int J Nanomedicine
PUBLISHED: 07-07-2011
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This study concerns the encapsulation and controlled release of both hydrophobic and hydrophilic medications with one polymer, which are delivered together as a combined therapy to treat diseased tissue. To test our hypothesis that the novel PEG-graft-PLA (PEG, polyethylene glycol; PLA, polylactic acid) can deliver both the hydrophobic and hydrophilic medications on account of its amphiphility, charge, and graft structure, PEG-graft-PLA (molecular weight of PEG = 1900) with very low critical micelle concentration was synthesized. One hydrophilic (insulin) and one hydrophobic (naproxen) model medication were loaded in separately during its self-assembly in aqueous solution. The resulting nanoparticles (NPs) were narrowly distributed and spherical, with average particle size around 200 nm, zeta potential >-10 mV, and encapsulation efficiency >50%. The NPs realized controlled release of insulin and naproxen for over 24 and 160 hours, respectively. Specifically, the bioactivity of the insulin released from the NPs was maintained. Owing to encapsulation, both for hydrophobic and hydrophilic medicines, and NPs obtained with similar size and zeta potential, as well as maintenance of bioactivity of loaded protein, we expect the applications of PEG-graft-PLA NPs in combination therapy.
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An empirical analysis of overlap publication in Chinese language and English research manuscripts.
PLoS ONE
PUBLISHED: 06-18-2011
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There are a number of sound justifications for publishing nearly identical information in Chinese and English medical journals, assuming several conditions are met. Although overlap publication is perceived as undesirable and ethically questionable in Europe and North America, it may serve an important function in some regions where English is not the native tongue. There is no empirical data on the nature and degree of overlap publication in English and Chinese language journals.
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Characteristics and antioxidant activity of Maillard reaction products from psicose-lysine and fructose-lysine model systems.
J. Food Sci.
PUBLISHED: 03-16-2011
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D-Psicose, an epimer of D-fructose isomerized at C-3 position, is a rare ketohexose that is thought to be beneficial for obese people and diabetic patients as a noncaloric sweetener. In the present study, model Maillard reaction products were obtained from D-psicose (or D-fructose) and L-lysine heating at 120 °C up to 8 h with the initial pH 9.0. The changes in pH, UV-vis absorbance, and free amino groups during the reaction were detected. Moreover, the antioxidant potential of the Maillard reaction products at different intervals was investigated. Although there was almost no difference in the oxygen radical absorbance capacity, the Maillard reaction products from psicose performed better than that from fructose in the radical-scavenging activity of 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt and 1, 1,-diphenyl-2-picryl-hydrazyl. The reducing power of the Maillard reaction products from psicose was also stronger than that from fructose. These results indicated that psicose played an effective role in the Maillard reaction and its Maillard reaction products could act as potential antioxidants in food industry.
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Semiparametric estimation for joint modeling of colorectal cancer risk and functional biomarkers measured with errors.
Biom J
PUBLISHED: 03-15-2011
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This research is motivated by a pilot colorectal adenoma study, where the outcome of interest is the presence of colorectal adenoma representing risk for colorectal cancer, and the predictors of interest are protein biomarkers that are repeatedly measured with errors along the length of a microscopic structure in the human colon, the colon crypt. Biomarkers of this type are referred to as functional biomarkers. The investigators are interested in identifying features of functional biomarkers that are associated with risk for colorectal cancer. In this paper, we investigate a joint modeling approach, where the binary clinical outcome is modeled using a logistic regression model with the unobserved true functional biomarkers as the predictors. Most existing methods are developed either for linear models or for functional biomarkers measured without errors and cannot be directly applied to our data. The applicable methods include a two-step method and a maximum likelihood method, which have some limitations. We propose a robust semiparametric method to overcome the limitations of the existing methods. We study the properties of the proposed method, and show in simulations that it compares favorably with other methods and also offers significant savings in CPU time. We analyze the pilot colorectal adenoma data and show that expression levels of AFC, a tumor suppressor gene, in the transitional area from the proliferation zone to the differentiation zone of colon crypts are likely to be associated with risk for colorectal cancer. Given the relatively small sample size in the pilot study, our results need to be validated in the future full-scale studies.
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The retinoblastoma protein/p16 INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma.
Histopathology
PUBLISHED: 02-16-2011
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The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell-cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell-cycle proteins: p53, p21, p16(INK4A) and retinoblastoma (RB) protein.
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Nitroxoline (8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than clioquinol (5-chloro-7-iodo-8-quinoline).
Cancer Lett.
PUBLISHED: 02-14-2011
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Clioquinol has been shown to have anticancer activity both in vitro and in vivo. The present study compared the cytotoxicity of clioquinol with six analogues using human cancer cell lines. Of the analogues tested, 8-hydroxy-5-nitroquinoline (NQ) was the most toxic, with an IC(50) that was five to ten fold lower than that of other congeners. Its activity was enhanced by copper, but not zinc, and the use of a zinc-sensitive fluorophore showed that unlike clioquinol, NQ is not a zinc ionophore. NQ increased intracellular reactive oxygen species generation, an effect that was significantly enhanced by the addition of copper at levels approximately the same as those found in human plasma. NQ has been used in humans for the treatment of urinary infections. NQ is an 8-hydroxyquinoline derivative that is more potent than the halogenated 8-hydroxyquinolines, and it may be less neurotoxic because it lacks zinc ionophore activity. NQ is another clinically used anti-microbial agent whose properties suggest that it may be useful in treating cancer.
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The dynamic face of HIV-1 subtypes among men who have sex with men in Beijing, China.
Curr. HIV Res.
PUBLISHED: 01-07-2011
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The rapid increase of HIV-1 prevalence among Chinese men who have sex with men (MSM) provides an impetus for the acquisition of molecular epidemiologic information from this population. We conducted four serial cross-sectional surveys during year 2005-2009 and observed that the composition of HIV-1 subtypes was dynamically changing with from clade B to CRF01_AE from years 2005-2009. HIV-1 infection in this population includes the persistent circulation of multiple HIV-1 subtypes and complex new recombinants.
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Longitudinal Image Analysis of Tumor/Healthy Brain Change in Contrast Uptake Induced by Radiation.
J R Stat Soc Ser C Appl Stat
PUBLISHED: 12-07-2010
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This work is motivated by a quantitative Magnetic Resonance Imaging study of the differential tumor/healthy tissue change in contrast uptake induced by radiation. The goal is to determine the time in which there is maximal contrast uptake (a surrogate for permeability) in the tumor relative to healthy tissue. A notable feature of the data is its spatial heterogeneity. Zhang, Johnson, Little, and Cao (2008a and 2008b) discuss two parallel approaches to "denoise" a single image of change in contrast uptake from baseline to one follow-up visit of interest. In this work we extend the image model to explore the longitudinal profile of the tumor/healthy tissue contrast uptake in multiple images over time. We fit a two-stage model. First, we propose a longitudinal image model for each subject. This model simultaneously accounts for the spatial and temporal correlation and denoises the observed images by borrowing strength both across neighboring pixels and over time. We propose to use the Mann-Whitney U statistic to summarize the tumor contrast uptake relative to healthy tissue. In the second stage, we fit a population model to the U statistic and estimate when it achieves its maximum. Our initial findings suggest that the maximal contrast uptake of the tumor core relative to healthy tissue peaks around three weeks after initiation of radiotherapy, though this warrants further investigation.
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MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells.
J. Biol. Chem.
PUBLISHED: 11-08-2010
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Tissue factor has been recognized as a regulator of tumor angiogenesis and metastasis. The tissue factor gene is selectively expressed in highly invasive breast cancer cells, and the mechanisms regulating tissue factor expression in these cells remain unclear. This study demonstrates that microRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells, providing a molecular basis for the selective expression of the tissue factor gene. Tissue factor protein was barely detectable in MCF-7, T47D, and ZR-75-1 cells (less invasive breast lines) but was expressed at a significantly higher level in MDA-MB-231 and BT-20 cells (invasive breast lines) as assayed by Western blot. The tissue factor gene promoter was activated, and forced expression of tissue factor cDNA was achieved in MCF-7 cells, implying that the 3-UTR of the tissue factor transcript is responsible for the suppression of tissue factor expression. Bioinformatics analysis predicted microRNA-binding sites for miR-19, miR-20, and miR-106b in the 3-UTR of the tissue factor transcript. Reporter gene assay using the TF-3-UTR luciferase reporter construct confirmed that the 3-UTR negatively regulates gene expression in MCF-7 cells, an effect reversed by deletion of the miR-19-binding site. Application of the miR-19 inhibitor induces endogenous tissue factor expression in MCF-7 cells, and overexpression of miR-19 down-regulates tissue factor expression in MDA-MB-231 cells. RT-PCR analysis using cDNA made from Ago2-immunoprecipitated RNA samples confirmed that Ago2 binds preferentially to tissue factor 3-UTR in MCF-7 cells, as compared with MDA-MB-231 cells, consistent with the observation that miR-19 levels are higher in MCF-7 cells.
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[Process strategy for ethanol production from lignocellulose feedstock under extremely low water usage and high solids loading conditions].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 10-20-2010
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The massive water and steam are consumed in the production of cellulose ethanol, which correspondingly results in the significant increase of energy cost, waster water discharge and production cost as well. In this study, the process strategy under extremely low water usage and high solids loading of corn stover was investigated experimentally and computationally. The novel pretreatment technology with zero waste water discharge was developed; in which a unique biodetoxification method using a kerosene fungus strain Amorphotheca resinae ZN1 to degrade the lignocellulose derived inhibitors was applied. With high solids loading of pretreated corn stover, high ethanol titer was achieved in the simultaneous saccharification and fermentation process, and the scale-up principles were studied. Furthermore, the flowsheet simulation of the whole process was carried out with the Aspen plus based physical database, and the integrated process developed was tested in the biorefinery mini-plant. Finally, the core technologies were applied in the cellulose ethanol demonstration plant, which paved a way for the establishment of an energy saving and environment friendly technology of lignocellulose biotransformation with industry application potential.
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Robust estimation of area under ROC curve using auxiliary variables in the presence of missing biomarker values.
Biometrics
PUBLISHED: 09-03-2010
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In medical research, the receiver operating characteristic (ROC) curves can be used to evaluate the performance of biomarkers for diagnosing diseases or predicting the risk of developing a disease in the future. The area under the ROC curve (ROC AUC), as a summary measure of ROC curves, is widely utilized, especially when comparing multiple ROC curves. In observational studies, the estimation of the AUC is often complicated by the presence of missing biomarker values, which means that the existing estimators of the AUC are potentially biased. In this article, we develop robust statistical methods for estimating the ROC AUC and the proposed methods use information from auxiliary variables that are potentially predictive of the missingness of the biomarkers or the missing biomarker values. We are particularly interested in auxiliary variables that are predictive of the missing biomarker values. In the case of missing at random (MAR), that is, missingness of biomarker values only depends on the observed data, our estimators have the attractive feature of being consistent if one correctly specifies, conditional on auxiliary variables and disease status, either the model for the probabilities of being missing or the model for the biomarker values. In the case of missing not at random (MNAR), that is, missingness may depend on the unobserved biomarker values, we propose a sensitivity analysis to assess the impact of MNAR on the estimation of the ROC AUC. The asymptotic properties of the proposed estimators are studied and their finite-sample behaviors are evaluated in simulation studies. The methods are further illustrated using data from a study of maternal depression during pregnancy.
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Correlates of incident infections for HIV, syphilis, and hepatitis B virus in a cohort of men who have sex with men in Beijing.
AIDS Patient Care STDS
PUBLISHED: 08-25-2010
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Recent data suggest that the prevalence of HIV/syphilis infections among men who have sex with men (MSM) in China increased rapidly. This cohort study was to assess the correlates of the incident infections for HIV, syphilis, and hepatitis B virus (HBV) among sexually active and HIV-negative MSM in China. A cohort of 507 HIV-seronegative MSM was recruited from November 2006 to February 2007. Sociodemographics, sexual and drug use behaviors, uptake of HIV-prevention services, and HIV, syphilis, and HBV seroconversions were assessed at 6- and 12- month follow-up. The incidence rates were 2.6 per 100 person-years for HIV, 16.9 per 100 person-years for syphilis, and 3.3 per 100 person-years for HBV. Multivariate Cox regression analyses showed that syphilis infection (hazard ratio [HR] = 3.6; 95% confidence interval [CI]: 1.1-11.6) and no perceived risk of HIV infection (HR = 6.0; 95% CI: 1.6-22.7) were independently associated with HIV seroconversion. Predictors for syphilis seroconversion included less education (HR = 1.87; 95% CI: 1.1-3.3), found male sex partners through bathhouses/public washrooms/parks (HR = 2.19; 95% CI: 1.2-4.0), drank alcohol 4 or more times monthly (HR = 1.95; 95% CI: 1.1-3.6), and had sexually transmitted diseases (HR = 2.65; 95% CI: 1.5-4.5). The only predictor for incident HBV seroconvension was having more male sex partners in the past 3 months (HR = 11.8; 95% CI: 1.5-90.4). Alarmingly high incidence rates of HIV, syphilis, and HBV were found among MSM concurrently with high prevalent risky behaviors and low uptakes of health care services. The findings of this study underscore the urgent needs for a comprehensive intervention strategy to curtail the rapid spread of HIV, syphilis, and HBV.
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A Bayesian Image Analysis of Radiation Induced Changes in Tumor Vascular Permeability.
Bayesian Anal
PUBLISHED: 05-08-2010
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This work is motivated by a quantitative Magnetic Resonance Imaging study of the relative change in tumor vascular permeability during the course of radiation therapy. The differences in tumor and healthy brain tissue physiology and pathology constitute a notable feature of the image data-spatial heterogeneity with respect to its contrast uptake profile (a surrogate for permeability) and radiation induced changes in this profile. To account for these spatial aspects of the data, we employ a Gaussian hidden Markov random field (MRF) model. The model incorporates a latent set of discrete labels from the MRF governed by a spatial regularization parameter. We estimate the MRF regularization parameter and treat the number of MRF states as a random variable and estimate it via a reversible jump Markov chain Monte Carlo algorithm. We conduct simulation studies to examine the performance of the model and compare it with a recently proposed method using the Expectation-Maximization (EM) algorithm. Simulation results show that the Bayesian algorithm performs as well, if not slightly better than the EM based algorithm. Results on real data suggest that the tumor "core" vascular permeability increases relative to healthy tissue three weeks after starting radiotherapy, which may be an opportune time to initiate chemotherapy and warrants further investigation.
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Stochastic modeling and prediction for accrual in clinical trials.
Stat Med
PUBLISHED: 01-19-2010
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Patient accrual in clinical trials is a topic of interest for important practical reasons. It has implications in both the initial planning and ongoing monitoring of trials. Slow accrual is of particular concern when it leads to reduced sample size. Although accrual in clinical trials has been studied and its estimation has been proposed and implemented, the existing methods are usually over-simplified by assuming a constant or piecewise constant accrual rate, and more flexible and realistic methods are needed. In this paper, we discuss a principled framework to monitor and predict trial accrual. We model trial accrual using a non-homogeneous Poisson process and model the underlying time-dependent accrual rate using cubic B-splines. The statistical inference and prediction procedure for the model are studied in a Bayesian paradigm. We conduct simulation studies to investigate the performance of the proposed approach and compare with a constant accrual rate model discussed by Gajewski et al. (Statist. Med. 2008; 27: 2328-2340). With satisfactory results, we illustrate the proposed method using accrual data from a real oncology trial. Our results show that the proposed model is more robust and achieves substantially better performance compared with the existing methods.
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Risk factors for syphilis and prevalence of HIV, hepatitis B and C among men who have sex with men in Beijing, China: implications for HIV prevention.
AIDS Behav
PUBLISHED: 09-10-2009
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To examine the correlates for syphilis and the prevalence for HIV, hepatitis B, hepatitis C among men-who-have-sex-with-men (MSM) in Beijing, China. A total of 541 MSM was recruited using peer-referral, community outreach, and Internet. Questionnaire-based interviews provided information including, demographics, sexual and other risk behaviors. HIV prevalence was 4.8%, syphilis 19.8%, HCV 0.4% and HBsAg 6.5%. The median number of lifetime male sex partners was ten. In the past 3 months, 20.7% drank alcohol > or =1 times per week. In the past month, 21.3 and 14.6% had unprotected anal intercourse with regular and casual male sex partners, respectively. Syphilis infection was associated with less education, alcohol use, finding male sex partners through bathhouses/public washrooms/parks, and diagnoses of sexual transmitted diseases (STDs). Syphilis is now epidemic among Beijings MSM. Prevention efforts are urgent as HIV prevalence is already near 5%. Education, condom promotion, STD control, and alcohol-related intervention are needed urgently.
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Incidence of HIV-1, syphilis, hepatitis B, and hepatitis C virus infections and predictors associated with retention in a 12-month follow-up study among men who have sex with men in Beijing, China.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-28-2009
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To investigate the incidence of HIV-1, syphilis, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections and predictors associated with retention in a 12-month follow-up study among men who have sex with men (MSM) in Beijing, China.
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HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis.
Mod. Pathol.
PUBLISHED: 05-22-2009
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Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16(INK4A) and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16(INK4A) and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16(INK4A) and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16(INK4A) expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.
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Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3.
J. Clin. Oncol.
PUBLISHED: 05-18-2009
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PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2) as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan. Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia. CONCLUSION Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.
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Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study.
Cancer
PUBLISHED: 04-22-2009
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Irinotecan-based chemotherapy regimens are 1 option for treatment of metastatic colorectal cancer (mCRC). The authors report the safety and efficacy of such regimens in elderly patients using a large phase III trial (bolus, infusional, or capecitabine with camptostar-celecoxib [BICC-C]) cohort.
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Screening of oleaginous yeast strains tolerant to lignocellulose degradation compounds.
Appl. Biochem. Biotechnol.
PUBLISHED: 01-21-2009
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High cost of triacylglycerol lipid feedstock is the major barrier for commercial production of biodiesel. The fermentation of oleaginous yeasts for lipid production using lignocellulose biomass provides a practical option with high economic competitiveness. In this paper, the typical oleaginous yeast strains were screened under the pressure of lignocellulose degradation compounds for selection of the optimal strains tolerant to lignocellulose. The inhibitory effect of lignocellulose degradation products on the oleaginous yeast fermentation was carefully investigated. Preliminary screening was carried out in the minimum nutritious medium without adding any expensive complex ingredients then was carried out in the lignocellulosic hydrolysate pretreated by dilute sulfuric acid. Seven typical lignocellulose degradation products formed in various pretreatment and hydrolysis processing were selected as the model inhibitors, including three organic acids, two furan compounds, and two phenol derivatives. The inhibition of the degradation compounds on the cell growth and lipid productivity of the selected oleaginous yeasts were examined. Acetic acid, formic acid, furfural, and vanillin were found to be the strong inhibitors for the fermentation of oleaginous yeasts, while levulinic acid, 5-hydroxymethylfurfural, and hydroxybenzaldehyde were relatively weak inhibitors. Trichosporon cutaneum 2.1374 was found to be the most adopted strain to the lignocellulose degradation compounds.
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Inhibition performance of lignocellulose degradation products on industrial cellulase enzymes during cellulose hydrolysis.
Appl. Biochem. Biotechnol.
PUBLISHED: 01-07-2009
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This study examined the inhibition performance by the major lignocellulose degradation products, including organic acids, furan derivatives, lignin derivatives, and ethanol, on a broadly used commercial cellulase enzyme Spezyme CP (Genencor International, Rochester, NY, USA) to cellulose hydrolysis at both the well-mixing state (shaking flask) and the static state (test tube). The cellulase activity in the cellulase complex of Spezyme CP was assumed to be one single "cellulase", and the apparent kinetic parameters of this cellulase enzyme were measured as an approximate index of the inhibitory effect to the industrial cellulase enzyme. The inhibition performance of these degradation products was compared and analyzed using the determined apparent kinetic parameters. All the degradation products strongly inhibit the cellulose hydrolysis by cellulase enzyme, and the inhibitions on cellulase were all competitive type. The order of the inhibition strength by the lignocellulose degradation products to cellulase is lignin derivatives > furan derivatives > organic acids > ethanol. This study gave a quantitative view to the enzymatic hydrolysis of lignocellulose under the inhibition performance of the lignocellulose degradation products and will help to understand the lignocellulose recalcitrance to enzyme hydrolysis.
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Modeling clinical outcome using multiple correlated functional biomarkers: A Bayesian approach.
Stat Methods Med Res
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In some biomedical studies, biomarkers are measured repeatedly along some spatial structure or over time and are subject to measurement error. In these studies, it is often of interest to evaluate associations between a clinical endpoint and these biomarkers (also known as functional biomarkers). There are potentially two levels of correlation in such data, namely, between repeated measurements of a biomarker from the same subject and between multiple biomarkers from the same subject; none of the existing methods accounts for correlation between multiple functional biomarkers. We propose a Bayesian approach to model a clinical outcome of interest (e.g. risk for colorectal cancer) in the presence of multiple functional biomarkers while accounting for potential correlation. Our simulations show that the proposed approach achieves good performance in finite samples under various settings. In the presence of substantial or moderate correlation, the proposed approach outperforms an existing approach that does not account for correlation. The proposed approach is applied to a study of biomarkers of risk for colorectal neoplasms and our results show that the risk for colorectal cancer is associated with two functional biomarkers, APC and TGF-?, in particular, with their values in the region between the proliferating and differentiating zones of colorectal crypts.
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Joint monitoring and prediction of accrual and event times in clinical trials.
Biom J
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In many clinical trials, the primary endpoint is time to an event of interest, for example, time to cardiac attack or tumor progression, and the statistical power of these trials is primarily driven by the number of events observed during the trials. In such trials, the number of events observed is impacted not only by the number of subjects enrolled but also by other factors including the event rate and the follow-up duration. Consequently, it is important for investigators to be able to monitor and predict accurately patient accrual and event times so as to predict the times of interim and final analyses and enable efficient allocation of research resources, which have long been recognized as important aspects of trial design and conduct. The existing methods for prediction of event times all assume that patient accrual follows a Poisson process with a constant Poisson rate over time; however, it is fairly common in real-life clinical trials that the Poisson rate changes over time. In this paper, we propose a Bayesian joint modeling approach for monitoring and prediction of accrual and event times in clinical trials. We employ a nonhomogeneous Poisson process to model patient accrual and a parametric or nonparametric model for the event and loss to follow-up processes. Compared to existing methods, our proposed methods are more flexible and robust in that we model accrual and event/loss-to-follow-up times jointly and allow the underlying accrual rates to change over time. We evaluate the performance of the proposed methods through simulation studies and illustrate the methods using data from a real oncology trial.
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Modeling and prediction of subject accrual and event times in clinical trials: a systematic review.
Clin Trials
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Modeling and prediction of subject accrual and event times in clinical trials has been a topic of considerable interest for important practical reasons. It has implications not only at the initial planning stage of a trial but also on its ongoing monitoring.
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[Analysis of 20 sulfonamides in sewage sludge by high performance liquid chromatography tandem mass spectrometry].
Wei Sheng Yan Jiu
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To develop a comprehensive method for simultaneous analysis of 20 sulfonamides in sewage sludge by liquid chromatography tandem mass spectrometry (LC-MS/MS).
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A simplified filter paper assay method of cellulase enzymes based on HPLC analysis.
Appl. Biochem. Biotechnol.
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A simplified filter paper assay (FPA) method of cellulase enzymes was proposed based on high-performance liquid chromatography (HPLC) measurement. The method was according to the sum of glucose and cellobiose concentrations measured by HPLC that was able to be correlated with filter paper units (FPU) of the cellulase enzymes assayed by the traditional FPA method, regardless of the differences in the sources, activities, and components of the cellulases. This simple and quick assay method for the cellulase enzymes provided another parameter of the ratio of glucose to cellobiose (G/C ratio) representing the capacity of cellulase enzymes degrading cellulose into fermentable monomeric sugars.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.