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Augmented Reality (AR) is a technology that can turn virtual objects in the form of two dimensions (2D) or three dimensions (3D) into an object that looks real, then able to display objects in real-time. Using AR technology, you can visualize learning material into 3D objects to make it easier to understand when using it as a learning medium. This research aims to develop an AR application with multiple marker features that can be used as an interactive learning medium. The method used is Research and Development (R&D), and the development model used is 4D. The evaluation used was the Software Usability Measurement Inventory (SUMI), involving 11th-grade which involved 30 students consisting of 20 male students and 10 female students, the parameters assessed in this evaluation were between others are Efficiency, Affect, Helpfulness, Control, and Learnability. Based on the analysis performed on these parameters, the results show that all five parameters obtain valid and reliable results for each parameter in the validity and reliability tests with a Cronbach's alpha score of 0.934 (Efficiency), 0.868 (Affect), 0.917 (Helpfulness), 0.878 (Control), and 0.919 (Learnability). Thus, this multiple marker-based interactive learning media, Augmented Reality (AR), can be used in learning activities.

In disease screening, a biomarker combination developed by combining multiple markers tends to have a higher sensitivity than an individual marker. Parametric methods for marker combination rely on the inverse of covariance matrices, which is often a non-trivial problem for high-dimensional data generated by modern high-throughput technologies. Additionally, another common problem in disease diagnosis is the existence of limit of detection (LOD) for an instrument – that is, when a biomarker's value falls below the limit, it cannot be observed and is assigned an NA value. To handle these two challenges in combining high-dimensional biomarkers with the presence of LOD, we propose a resample-replace lasso procedure. We first impute the values below LOD and then use the graphical lasso method to estimate the means and precision matrices for the high-dimensional biomarkers. The simulation results show that our method outperforms alternative methods such as either substitute NA values with LOD values or remove observations that have NA values. A real case analysis on a protein profiling study of glioblastoma patients on their survival status indicates that the biomarker combination obtained through the proposed method is more accurate in distinguishing between two groups.

Dietary analysis using DNA metabarcoding is a powerful tool that is increasingly being used to further our knowledge of trophic interactions in highly complex food webs but is not without limitations. Omnivores, the most generalist of consumers, pose unique challenges when using such methods. Here, we provide the rationale to understand the problems associated with analysing the complex diets of omnivores. By reviewing existing metabarcoding studies of omnivorous diet, and constructing hypothetical scenarios arising from each, we outline that great caution is required when interpreting sequencing data in such cases. In essence, the problems of accidental consumption and secondary ingestion are significant sources of error when investigating omnivorous diets. The integration of multiple high throughput sequencing markers increases the taxonomic breadth of taxa detected but we reveal how some detections may be misleading. Disentangling which taxa have been deliberately or accidentally consumed by the focal omnivore is challenging and can falsely emphasise those that were not intentionally consumed, obscuring biologically meaningful interactions. Although we suggest ways to disentangle these issues, we urge that the results of such analyses should be interpreted with caution and all possible scenarios for the presence of biota within omnivores given due consideration.

Cardimap tablet is a polyherbal formulation manufactured by Maharishi Ayurveda and used as an antihypertensive. The Ayurvedic formulation contains Rauwolfia serpentina, Nardostachys jatamansi, Convolvulus pluricaulis, Bacopa monnieri, Piper longum, and hence contains five markers, namely, reserpine, lupeol, scopoletine, bacoside A and piperine. This paper reports the standardization of Cardimap tablet according to World Health Organization (WHO) guideline and also by high-performance thin-layer chromatography method for the presence of the markers reserpine, lupeol, scopoletine, bacoside A and piperine. Both marketed and lab preparation complied all parameters according to WHO guideline and each marker compound showed a linear relationship in the concentration range 1‒2 µg per spot for reserpine, 2.5‒4.5 µg per spot for scopoletine, 10–50 µg per spot for piperine, 12–24 µg per spot for bacoside A and 1‒5 µg per spot lupeol. The proposed method was found to be precise, specific, and accurate, with a recovery of 98‒102%, and hence can be used for the routine analysis of this formulation.

Introduced species can exert disproportionately negative effects on island ecosystems, but their potential role as food for native consumers is poorly studied. Telfair's skinks are endemic omnivores living on Round Island, Mauritius, a globally significant site of biodiversity conservation. We aimed to determine the dietary diversity and key trophic interactions of Telfair's skinks, whether introduced species are frequently consumed, and if diet composition changes seasonally between male and female skinks. We used DNA metabarcoding of skink fecal samples to identify animals (COI) and plants (ITS2) consumed by skinks. There were 389 dietary presence counts belonging to 77 dietary taxa found across the 73 Telfair's skink fecal samples. Introduced taxa were cumulatively consumed more frequently than other categories, accounting for 49.4% of all detections, compared to cryptogenic (20.6%), native (20.6%), and endemic taxa (9.5%). The most frequently consumed introduced species was the ant, Pheidole megacephala, present in 40% of samples. Blue latan palm, Latania loddigesii, was the most frequently consumed endemic species, present in 33% of samples but was only detected in the dry season, when fruits are produced. We found a strong seasonal difference in diet composition explained by the presence of certain plant species solely or primarily in one season and a marked increase in the consumption of animal prey in the dry season. Male and female skinks consumed several taxa at different frequencies. These results present a valuable perspective on the role of introduced species in the trophic network of their invaded ecosystem. Both native and introduced species provide nutritional resources for skinks, and this may have management implications in the context of species conservation and island restoration.

Background: Transfusion-transmissible infections are well-known global health challenges. The present study is proposed to investigate the seropositivity of anti-HIV1/2, anti-HCV, HBsAg, and anti-T.pallidum among volunteer blood donors of Kosti Obstetrics and Gynecology Hospital. Methods: Our study was conducted in a cross-sectional retrospective manner. The data of donors who attended Kosti Obstetrics and Gynecology Hospital throughout 2016 to 2018 were reviewed and retrieved manually from blood bank records. Results: Out of 8139 donors, 22.52% were seropositive for serological markers of TTIs and 1.67% were seropositive for at least two serological markers of TTIs. The overall seropositivity rate of anti-HIV1/2, HBsAg, anti-HCV, and anti-T.pallidum was 1.77%, 6.07%, 1.14%, and 11.87%, respectively (p &lt, 0.000). Anti-T.pallidum was the most frequently detected (p &lt, 0.000) marker across all study variables. TTIs seroprevalence was significantly (p &lt, 0.000) varied according to the age, residence, occupations, and blood groups. Notably, there was a rising trend in the rate of anti-HIV1/2 and seropositivity for more than one marker with age (p &lt, 0.000). Regionally, rural area residents had a higher rate of anti-HIV1/2 (2.20%), HBsAg (6.31%), anti-HCV (1.42%), anti-T.pallidum (18.38%), and multiple markers seropositivity (2.28%) compared to urban areas. Between occupations, the highest rate of anti-HIV1/2 (p = 0.497), HBsAg (p = 0.003), anti-HCV (p = 0.385), anti-T.pallidum (p &lt, 0.000), and multiple markers seropositivity (p &lt, 0.000) were detected in farmers. Regarding the screening, we also found that the frequency of anti-T.pallidum was significantly (p = 0.004) higher in donors that carry the AB+ve blood group, whereas anti-HCV (1.83%) was more frequent in O−ve blood groups (p = 0.004). Anti-T.pallidum+HBsAg was the most frequently (1.22%) co-occurring marker. In contrast, anti-T.pallidum+anti-HIV1/2+HBsAg was the lowest frequency marker (p &lt, 0.000). Conclusions: The study showed an alarming rate of TTIs, which suggests the requirement for comprehensive surveillance and health education programs.

Variation among markers has the potential to disadvantage students by contributing to a discrepancy in assessments in higher education settings. In this study, we extended a previous study that analyzed first-year students’ results in a Business Faculty within an Australian university to understand the extent of variation within and between multiple markers and across multiple courses. The study investigated the potential influence of quality of rubrics and associated documentation provided as marker guidance. Results indicated that specific features of rubrics, such as the inclusion of clear indicators of quality, had an observable effect on marker variation.

Critical approaches to inclusive education seek to transform educational systems to increase access, participation, and achievement for students at the intersections of multiple markers of ...

Multimarker fluorescence analysis of tissue specimens offers the opportunity to probe the expression levels and locations of multiple markers in a single sample. Software is needed to fully capitalize on the advantages of this technology for sensitive, quantitative, and multiplexed data collection. A major challenge has been the automated identification and quantification of signals. We report on the software SignalFinder-IF, which meets that need. SignalFinder-IF uses a newly developed algorithm called Segment-Fit Thresholding, which showed robust performance for automated signal identification in side-by-side comparisons with several current methods. Two utilities provided with SignalFinder-IF enable downstream analyses. The first allows the quantification and mapping of relationships between an unlimited number of markers through user-defined sequences of AND, OR, and NOT operators. The second produces composite pictures of the signals or colocalization analysis on brightfield hematoxylin and eosin images, which is useful for understanding the morphologies and locations of cells meeting specific marker criteria. SignalFinder-IF enables high-throughput, rigorous analyses of whole-slide, multimarker data, and it promises to open new possibilities in many research and clinical applications.

Many consequences of ageing can be broadly attributed to the inability to maintain homeostasis. Multiple markers of ageing have been identified, including loss of protein homeostasis, increased inflammation, and declining metabolism. Although much effort has been focused on characterization of the ageing phenotype, much less is understood about the underlying causes of ageing. To address this gap, we outline the age-associated consequences of dysregulation of ‘Adaptive Homeostasis’ and its proposed contributing role as an accelerator of the ageing phenotype. Adaptive Homeostasis is a phenomenon, shared across cells and tissues of both simple and complex organisms, that enables the transient plastic expansion or contraction of the homeostatic range to modulate stress-protective systems (such as the Proteasome, the Immunoproteasome, and the Lon protease) in response to varying internal and external environments. The age-related rise in the baseline of stress-protective systems and the inability to increase beyond a physiological ceiling is likely a contributor to the reduction and loss of Adaptive Homeostasis. We propose that dysregulation of Adaptive Homeostasis in the final third of lifespan is a significant factor in the ageing process, while successful maintenance of Adaptive Homeostasis below a physiological ceiling results in extended longevity.

To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with persistent suspicious oral mucosal lesions (PSOML). Whole unstimulated saliva samples were collected from age-, sex-, and race-matched patients who had a lesion in the oral cavity and for whom open biopsies were performed. The patients included OSCC (n = 6), OED (n = 10), and PSOML (n = 32). Hydrophilic metabolites in saliva samples were comprehensively analyzed using capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC/OED from PSOML. Six metabolites were significantly different in OSCC/OED compared with PSOML. From these six metabolites, ornithine, o-hydroxybenzoate, and ribose 5-phosphate (R5P) were used to develop the MLR model, which resulted in a high value for the area under receiver operating characteristic curve (AUC 0.871, 95% confidential interval (CI) 0.760–0.982; p

Ubiquity (devices becoming part of the context) and transparency (devices not interfering with daily activities) are very significant in healthcare monitoring applications for elders. The present study undertakes a scoping review to map the literature on sensor-based unobtrusive monitoring of older adults’ frailty. We aim to determine what types of devices comply with unobtrusiveness requirements, which frailty markers have been unobtrusively assessed, which unsupervised devices have been tested, the relationships between sensor outcomes and frailty markers, and which devices can assess multiple markers. SCOPUS, PUBMED, and Web of Science were used to identify papers published 2010–2020. We selected 67 documents involving non-hospitalized older adults (65+ y.o.) and assessing frailty level or some specific frailty-marker with some sensor. Among the nine types of body worn sensors, only inertial measurement units (IMUs) on the waist and wrist-worn sensors comply with ubiquity. The former can transparently assess all variables but weight loss. Wrist-worn devices have not been tested in unsupervised conditions. Unsupervised presence detectors can predict frailty, slowness, performance, and physical activity. Waist IMUs and presence detectors are the most promising candidates for unobtrusive and unsupervised monitoring of frailty. Further research is necessary to give specific predictions of frailty level with unsupervised waist IMUs.

In recent years, environmental DNA analyses became increasingly integrated to detect and monitor the presence and abundance of rare organisms, especially in inaccessible aquatic habitats. Although it is generally proven that detection probabilities of eDNA surveys exceed those obtained via conventional techniques, these molecular approaches are, however, also subjected to detection limitations and levels of uncertainty. Besides improvements that can be made in terms of sampling design, volumes of filtered water, and the effective quantity of DNA that is finally analysed, the sensitivity of eDNA surveys is inherently determined by the number of target eDNA copies suspended in the water column. Here we show that multiplexing different primer/probe assays for the same species, but targeting amplicons situated at different loci, is a surprisingly overlooked aspect that can substantially contribute to reduce these limitations and increase the sensitivity of single-species detections. By empirically testing a large number of natural eDNA samples via ddPCR, we reveal that the use of multiple markers can significantly lower the LOD and LOQ of rare and elusive species, such as the invasive American bullfrog and the endangered European weather loach in a variety of different water bodies, such as ponds, lakes, streams, canals, etc. Especially at very low eDNA concentrations of both target species, our results showed that analysing mulitple loci significantly increased detection probabilities and lowered stochasticity effects, and thus ultimately reduces PCR costs when analysed in multiplex. The validation and use of more than one assay taregtting a single species, may further increase the confidence of positive detections. Finally, we illustrate that the implementation of internal positive controls (IPC's), is an absolute must for accurate validation of eDNA workflows and reliable interpretation of the generated data. IPC’s not only help to track down degraded and inhibited samples, to avoid false-negative detections, it also offers insights into extraction efficiency, indispensable for accurate quantification of population densities. Overall, our findings provide strong support that the multiplexing of multiple markers on different loci in combination with the use of internal positive controls ensures increased detection rates at very low eDNA concentrations and generates more robust and reliable data.

Background Immuno-oncology and targeted molecular therapies have acquired a central role in the treatment of multiple cancers. Consequently, high-throughput biomarker analysis and tumor immune profiling have seen an increased demand. Multiplexed immuno-assays are a powerful tool to address these needs, but still time- and resource-consuming. Our goal is to develop a fast and automated high-plex fluorescent immunostaining procedure, using a microfluidic-based device, that can be easily implemented as routine assay. Materials and Methods Protocol optimization has been performed on FFPE sections of human tonsil. Slides were manually deparaffinized before being entirely processed (antigen-retrieval, staining, elution and counterstaining) by Lunaphore’s autostainer, LabSatTM. The OPAL® tyramide signal amplification (TSA) system was used as detection method. Signal analysis was done on Mantra® workstation. The 6-plex panel was composed of FoxP3, PD-L1, PD-1, CD68, CD8 and pan-CK, plus DAPI counterstaining. Protocols were subsequently transferred on NSCLC representative specimens and finally assessed on a TMA cohort. Results Our platform allowed to reduce drastically the incubation times due to active transport of reagents across the tissue. Thereby, the automated 6-plex assay could be performed in less than 4h30min, within the timeframe of a single IHC standard assay. Protocol optimization resulted in high signal-to-background ratio for each marker and removal of previous step antibodies over 99%. LabSatTM also guaranteed remarkable signal uniformity, even over large tissue sections with less than 10% signal gradient over 1 cm. On NSCLC samples, the detected pattern and expression level for all six biomarkers were comparable to the standard chromogenic stainings performed with standard automated tissue stainer. Conclusions LabSatTM autostainer enables multistaining runs in a timely manner, opening the perspective of rapid simultaneous detection of multiple markers in their morphological context on a routine-based approach. This versatile analysis tool can offer a better and more quantitative understanding of tumor heterogeneity and microenvironmental interactions, allowing advances in targeted therapy for lung cancer as well as broader spectrum of malignancies. Disclosure Information A. Kehren: A. Employment (full or part-time); Significant; Lunaphore Technologies SA. C. Other Research Support (supplies, equipment, receipt of drugs or other in-kind support); Significant; Akoya Biosciences. M.G. Procopio: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Significant; KTI grant (Schweiz). B. Pelz: A. Employment (full or part-time); Significant; Lunaphore Technologies SA. C. Other Research Support (supplies, equipment, receipt of drugs or other in-kind support); Significant; Akoya Biosciences. Z. Siddiqui: A. Employment (full or part-time); Modest; Lunaphore Technologies SA. K. Roman: A. Employment (full or part-time); Significant; Akoya Biosciences. S. Adnane: A. Employment (full or part-time); Modest; Lunaphore Technologies SA. S. Brajkovic: A. Employment (full or part-time); Significant; Lunaphore Technologies SA. C. Hoyt: A. Employment (full or part-time); Significant; Akoya Biosciences. D.G. Dupouy: A. Employment (full or part-time); Significant; Lunaphore Technologies SA. E. Ownership Interest (stock, stock options, patent or other intellectual property); Significant; Lunaphore Technologies SA. A. Soltermann: A. Employment (full or part-time); Significant; Institut fur Klinische Pathologie Universitatsspital Zurich.

Optical measurement based on three linear charge-coupled devices (CCD) has prominent advantages in precise coordinate measurement and dynamic position tracking. However, it is difficult for the linear CCD optical measurement system to distinguish multiple markers when they are illuminated simultaneously, which leads to a marker matching problem. This paper proposes a new marker correspondence scheme to distinguish three markers in the linear CCD system by using four pairs of linear CCDs and cylindrical lenses. The relationship of projection points on four linear CCDs of one marker is derived. The analysis of the constraint equation is given, and the most suitable projection points which come from the markers are matched. The numerical simulation is conducted to demonstrate the feasibility of the proposed method, and the result shows that this approach enables the linear CCD measurement system to identify the correspondence relationship of three markers, thus breaks through the limitation that the linear CCD measurement system can only track one marker at a time.

Multispectral fluorescence imaging on formalin-fixed paraffin-embedded (FFPE) tissues enables the detection of multiple markers in a single tissue sample that can provide information about antigen coexpression and spatial distribution of the markers. However, a lack of suitable antibodies for formalin-fixed tissues may restrict the nature of markers that can be detected. In addition, the staining method is time-consuming. Here we describe a rapid method to perform multispectral fluorescence imaging on frozen tissues. The method includes the fluorophore combinations used, detailed steps for the staining of mouse and human frozen tissues, and the scanning, acquisition, and analysis procedures. For staining analysis, a commercially available semiautomated multispectral fluorescence imaging system is used. Through this method, up to six different markers were stained and detected in a single frozen tissue section. The machine learning analysis software can phenotype cells that can be used for quantitative analysis. The method described here for frozen tissues is useful for the detection of markers that cannot be detected in FFPE tissues or for which antibodies are not available for FFPE tissues.

International audience; Measuring the magnitude of reduction in HIV‐1 RNA levels accurately is difficult because many patients have a censored reduction due to the limit of detection (LOD) of the virologic assay being employed. The use of censored methods has improved the analysis of such reductions compared with crude methods but implies independent censoring. For HIV‐1 RNA reduction data, the value at which a patient's HIV‐1 RNA reduction becomes censored is mainly determined by the patient's baseline HIV‐1 RNA level. We suggest two possibilities based on modification of the redistribution to the right algorithm to handle the situation of dependence either from a single continuous marker, that is, the baseline HIV‐1 RNA level, or from multiple markers. Two series of simulation, one in the HIV‐1 RNA setting and one in the classical censoring setting, compared performance of the previous methods with our suggestions. Our proposed estimators show good performances when the dependent censoring is due to LOD. Overall, in the classical censoring setting, our suggestions perform as well as other methods including the Inverse Probability of Censoring Weighted and the Kaplan‐Meier imputation with Bootstrap. We applied those estimators to estimate the HIV‐1 RNA reduction at week 8 of 502 patients who received a raltegravir‐containing regimen and to data from the Mayo Clinic trial in primary biliary cirrhosis.

Rates of posttraumatic stress are elevated in individuals who have experienced childhood and/or cumulative trauma, and trauma appraisals have been suggested as a possible mediator of this effect. This study tested the proposed mediating role of trauma appraisals between both childhood and cumulative trauma, and two markers of trauma-related distress; posttraumatic stress and depression. Mediation models were developed and tested with data collected from a sample of trauma-exposed, treatment receiving adults (N = 106). Trauma appraisals fully mediated relationships between childhood trauma and PTSD/depression. Appraisals also mediated the relationships between cumulative trauma and depression. When appraisal subscales were simultaneously entered, alienation appraisals were the only significant mediator of these relationships. The study found support for the proposed mediating role of trauma appraisals between different forms of trauma and trauma related distress. Alienation appraisals were particularly emphasised.

PURPOSE OF REVIEW Epilepsy surgery is the therapy of choice for 30-40% of people with focal drug-resistant epilepsy. Currently only ∼60% of well selected patients become postsurgically seizure-free underlining the need for better tools to identify the epileptogenic zone. This article reviews the latest neurophysiological advances for EZ localization with emphasis on ictal EZ identification, interictal EZ markers, and noninvasive neurophysiological mapping procedures. RECENT FINDINGS We will review methods for computerized EZ assessment, summarize computational network approaches for outcome prediction and individualized surgical planning. We will discuss electrical stimulation as an option to reduce the time needed for presurgical work-up. We will summarize recent research regarding high-frequency oscillations, connectivity measures, and combinations of multiple markers using machine learning. This latter was shown to outperform single markers. The role of NREM sleep for best identification of the EZ interictally will be discussed. We will summarize recent large-scale studies using electrical or magnetic source imaging for clinical decision-making. SUMMARY New approaches based on technical advancements paired with artificial intelligence are on the horizon for better EZ identification. They are ultimately expected to result in a more efficient, less invasive, and less time-demanding presurgical investigation.

With the massification of higher education, it is easy for students to feel like a number, especially in a large enrolment subject with much of the learning occurring online. Large enrolments can present real challenges in design, management and standardisation of assessment practices. These challenges are intensified by reduced or absent face-to-face class time for online learners, heavy reliance upon sessional staff, issues of equity and consistency across multiple campuses (including online versus face-to-face) and multiple markers, establishing and maintaining student engagement, and finding ways to provide high-quality, individual feedback. These challenges often mean that established, best-practice pedagogy, which is usually designed, tested and evaluated in much smaller face-to-face contexts, requires modification to meet the needs of large online class teaching.

Introduction Cardiac function includes left ventricle ejection fraction, right ventricle function, diastolic function, and multiple markers of cardiac outflow. Markers of cardiac function associated with mortality are unknown. The purpose of this study was to determine markers of cardiac function associated with mortality in the elderly which represent cardiac frailty and the relative importance of these many measurements of cardiac function when compared with each other. Methods A retrospective review of patients who underwent focused rapid echocardiographic evaluations was performed from 2009 to 2014. Focused rapid echocardiographic evaluations are echocardiographic exams focusing on cardiac function rather than structure. Results Overall, 513 trauma patients received focused rapid echocardiographic evaluations. In elderly patients, mortality increase of 33.9% was seen with left ventricle ejection fraction less than 30% (p = 0.05), 28.5% with moderate right ventricle dysfunction (p = 0.03), and 18.5% with velocity time integral less than 18 cm (p = 0.02). Any level of diastolic dysfunction, cardiac output of less than 4 l/min, and cardiac index less than 2.5 l/min/m2 was not significantly associated with increased mortality in the elderly (not significant [NS] for all). In younger patients, a mortality increase of 68.1% was seen with grade 3–4 diastolic dysfunction (p2 not associated with mortality (NS for all). In logistic regression for elderly patients, only moderate right ventricle dysfunction was associated with mortality (odds ratio 4.321, 95% confidence interval 1.451–12.866, p = 0.009). Conclusions Markers of cardiac function associated with mortality vary with age. Right ventricle dysfunction may represent cardiac frailty, while diastolic dysfunction and left ventricle ejection fraction likely do not.

Platinum-based chemotherapy remains the cornerstone of treatment for many malignancies. However, although therapeutic efficiency varies greatly among individuals, there is a lack of pharmacogenomic biomarkers that can be used in clinical settings to identify chemosensitive patients and allow stratification. With the development of high-throughput screening techniques and systems biology approaches, a growing body of evidence has shown that platinum resistance is a multifactorial, multi-dimensional, dynamic process incorporating genetic background, tumor evolution and gut microbes. This review critically summarizes potential pharmacogenomic biomarkers for predicting the efficacy of platinum drugs and provides a comprehensive, time-varying perspective that integrates multiple markers.

The mortality of ovarian cancer is higher than any other female genital malignant tumors, while there exists a strong correlation between early-stage detection and cure for it. CA125 and HE4 are two most common and effective serum markers in recent screening research of ovarian cancer. This paper derives a sequential screening strategy for ovarian cancer by jointly modeling the longitudinal profiles of CA125 and HE4. We construct a Bayesian hierarchical mixture model with changepoint, and propose two approaches for diagnosis: the risk of cancer index and the hypothesis test on the true incidence time. We simulated a 7-year sequential screening research and compared with the standard approach based on a fixed cutoff level. Our approach achieves a 15% higher sensitivity for a fixed specificity, indicating that the sequential strategy combining multiple markers is more effective in the early-stage detection of ovarian cancer.

The combined use of multiple markers is considered a promising strategy in estimating the age of wounds. We sought to develop an "up, no change, or down" system and to explore how to combine and use various parameters. In total, 78 Sprague Dawley rats were divided randomly into a control group and contusion groups of 4-, 8-, 12-, 16-, 20-, 24-, 28-, 32-, 36-, 40-, 44-, and 48-h post-injury (n=6 per group). A contusion was produced in the right limb of the rats under diethyl ether anesthesia by a drop-ball technique; the animals were sacrificed at certain time points thereafter, using a lethal dose of pentobarbital. Levels of PUM2, TAB2, GJC1, and CHRNA1 mRNAs were detected in contused muscle using real-time PCR. An up, no change, or down system was developed with the relative quantities of the four mRNAs recorded as black, dark gray, or light gray boxes, representing up-, no change, or down-regulation of the gene of interest during wound repair. The four transcripts were combined and used as a marker cluster for color model analysis of each contusion group. Levels of PUM2, TAB2, and GJC1 mRNAs decreased, whereas that of CHRNA1 increased in wound repair (P

Chronic human immunodeficiency virus (HIV) infection, separately and in combination with highly active antiretroviral therapy (HAART) is closely associated with oxidative stress (OS). Most studies demonstrating redox imbalances in HIV-infected individuals have done so using conventional biochemical methodologies. The limited simultaneous detection of multiple OS markers within one sample is a major drawback of these methodologies and can be addressed through the use of metabonomics. HIV-metabonomic studies utilizing biofluids from HAART cohorts as the investigative source, are on the increase. Data from many of these studies identified metabolic markers indicative of HIV-induced OS, usually as an outcome of an untargeted metabonomics study. Untargeted studies cast a wide net for any and all detectable metabolites in complex mixtures. Given the prevalence of OS during HIV infection and antiviral treatment, it is perhaps not surprising that indicators of this malady would become evident during metabolite identification. At times, targeted studies for specific (non-OS) metabolites would also yield OS markers as an outcome. This review examines the findings of these studies by first providing the necessary background information on OS and the main ways in which free radicals/reactive oxygen species (ROS) produced during OS, cause biomolecular damage. This is followed by information on the biomarkers which come about as a result of free radical damage and the techniques used for assaying these stress indicators. The established links between elevated ROS and lowered antioxidants during HIV infection and the subsequent use of HAART is then presented followed by a review of the OS markers detected in HIV metabonomic studies to date. We identify gaps in HIV/HAART-associated OS research and finally suggest how these research gaps can be addressed through metabonomic analysis, specifically targeting the multiple markers of HIV-induced OS.