Journal articles: 'Multimarker model'

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Mohseni, AL Wagenaar SMJ van Kuijk, MEA Spaanderman, and C. Ghossein-Doha. "268. A multimarker model for aberrant cardiac geometry after PE." Pregnancy Hypertension 13 (October 2018): S115. http://dx.doi.org/10.1016/j.preghy.2018.08.339.

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Tsai, M. Y., C. K. Hsiao, and S. H. Wen. "A Bayesian Spatial Multimarker Genetic Random-Effect Model for Fine-Scale Mapping." Annals of Human Genetics 72, no. 5 (September 2008): 658–69. http://dx.doi.org/10.1111/j.1469-1809.2008.00459.x.

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Linke, Steven P., Troy M. Bremer, Christopher D. Herold, Guido Sauter, and Cornelius Diamond. "A multimarker model to predict outcome in tamoxifen-treated breast cancer patients." Clinical Cancer Research 12, no. 4 (February 15, 2006): 1175–83. http://dx.doi.org/10.1158/1078-0432.ccr-05-1562.

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Gould Rothberg, Bonnie E., Aaron J. Berger, Annette M. Molinaro, Antonio Subtil, Michael O. Krauthammer, Robert L. Camp, William R. Bradley, Stephan Ariyan, Harriet M. Kluger, and David L. Rimm. "Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms." Journal of Clinical Oncology 27, no. 34 (December 1, 2009): 5772–80. http://dx.doi.org/10.1200/jco.2009.22.8239.

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PurposeAs a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence.MethodsProtein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004.ResultsMultiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than –0.052, p21WAF1nuclear compartment AQUA score of more than 12.98, p16INK4Aln(non-nuclear/nuclear AQUA score ratio) of ≤ −0.083, β-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of ≤ 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts.ConclusionThis multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.

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Spelman, Richard J., Wouter Coppieters, Latifa Karim, Johan A. M. van Arendonk, and Henk Bovenhuis. "Quantitative Trait Loci Analysis for Five Milk Production Traits on Chromosome Six in the Dutch Holstein-Friesian Population." Genetics 144, no. 4 (December 1, 1996): 1799–807. http://dx.doi.org/10.1093/genetics/144.4.1799.

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Twenty Dutch Holstein-Friesian families, with a total of 715 sires, were evaluated in a granddaughter experiment design for marker-QTL associations. Five traits—milk, fat and protein yield and fat and protein percent—were analyzed. Across-family analysis was undertaken using multimarker regression principles. One and two QTL models were fitted. Critical values for the test statistic were calculated empirically by permuting the data. Individual trait distributions of permuted test statistics differed and, thus distributions, had to be calculated for each trait. Experimentwise critical values, which account for evaluating marker-QTL associations on all 29 autosomal bovine chromosomes and for five traits, were calculated. A QTL for protein percent was identified in one and two QTL models and was significant at the 1 and 2% level, respectively. Extending the multimarker regression approach to an analysis including two QTL was limited by families not being informative at all markers, which resulted in singularity. Below average heterozygosity for the first and last marker lowered information content for the first and last marker bracket. Highly informative markers at the ends of the mapped chromosome would overcome the decrease in information content in the first and last marker bracket and singularity for the two QTL model.

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Lee, Shin-Wha, Ha-Young Lee, Hyo Joo Bang, Hye-Jeong Song, Sek Won Kong, and Yong-Man Kim. "An Improved Prediction Model for Ovarian Cancer Using Urinary Biomarkers and a Novel Validation Strategy." International Journal of Molecular Sciences 20, no. 19 (October 5, 2019): 4938. http://dx.doi.org/10.3390/ijms20194938.

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This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples withOC(mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772–0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714–0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool.

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Kuznetsov, V. A., T. N. Enina, A. M. Soldatova, T. I. Petelina, S. M. Dyachkov, and L. A. Salamova. "Multimarker approach for assessing efficiency of cardiac resynchronization therapy in patients with sinus rhythm." Jounal of arrhythmology 27, no. 1 (June 4, 2020): 21–29. http://dx.doi.org/10.35336/va-2020-1-21-29.

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Purpose: to design mathematical model, that can predict positive response to cardiac resynchronization therapy (CRT) in patients with congestive heart failure (CHF) and sinus rhythm, according to complex analysis of neurohumoral and immune activation biomarkers, fibrosis, renal dysfunction, echocardiography.Material and methods: parameters of echocardiography, plasma levels of NT-proBNP, interleukins-1β, 6, 10, tumor necrosis factor α, С-reactive protein (СRP), matrix metalloproteinase-9 (ММР-9), tissue inhibitors of metalloproteinase 1 and 4, cystatin С (CYSTATIN) were studied in 40 CHF patients with sinus rhythm (65% coronary artery disease patients, 75% males, mean age 54.8±10.6 years old) during the period of maximum decrease of left ventricular end-systolic volume (LVESV) (mean duration 27.5 [11.1; 46.3] months). Responders (decrease in LVESV ≥15%) and non-responders (decrease in LVESV ˂15%) were identified.Results: the number of responders was 26 (65%). Initial set of variables included: age, left ventricular ejection fraction (EF), systolic pressure in the pulmonary artery, right ventricle size and NT-proBNP, СRP, ММР-9, CYSTATIN. According to logistic regression analysis, a model was created: F=3.231 + 0.344 х EF - 3.479 x CYSTATIN - 0.039 х ММР-9 - 0.638 х CRР. Prediction of response to CRT (P) was carried out using the equation: Р=1/(1+е(-F)); a less than 0.696 p-value was associated with membership of non-responders group; p-value greater than or equaled to 0.696 was associated with group of responders. The specificity of the model was 92.9%, sensitivity - 83.3%, AUC=0.952 (р˂0.001).Conclusions: the proposed model, based on assessment of left ventricular EF and laboratory data, that reflect key mechanisms of development and progression of CHF - immune inflammation, fibrosis, renal dysfunction, suggests a possible response to CRT.

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Yurkovetsky, Zoya, Steven Skates, Aleksey Lomakin, Brian Nolen, Trenton Pulsipher, Francesmary Modugno, Jeffrey Marks, et al. "Development of a Multimarker Assay for Early Detection of Ovarian Cancer." Journal of Clinical Oncology 28, no. 13 (May 1, 2010): 2159–66. http://dx.doi.org/10.1200/jco.2008.19.2484.

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PurposeEarly detection of ovarian cancer has great promise to improve clinical outcome.Patients and MethodsNinety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.ResultsA training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer.ConclusionA panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.

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Giurgea, Georgiana-Aura, Katrin Zlabinger, Alfred Gugerell, Dominika Lukovic, Bonni Syeda, Ljubica Mandic, Noemi Pavo, et al. "Multimarker Approach to Identify Patients with Coronary Artery Disease at High Risk for Subsequent Cardiac Adverse Events: The Multi-Biomarker Study." Biomolecules 10, no. 6 (June 15, 2020): 909. http://dx.doi.org/10.3390/biom10060909.

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In our prospective non-randomized, single-center cohort study (n = 161), we have evaluated a multimarker approach including S100 calcium binding protein A12 (S100A1), interleukin 1 like-receptor-4 (IL1R4), adrenomedullin, copeptin, neutrophil gelatinase-associated lipocalin (NGAL), soluble urokinase plasminogen activator receptor (suPAR), and ischemia modified albumin (IMA) in prediction of subsequent cardiac adverse events (AE) during 1-year follow-up in patients with coronary artery disease. The primary endpoint was to assess the combined discriminatory predictive value of the selected 7 biomarkers in prediction of AE (myocardial infarction, coronary revascularization, death, stroke, and hospitalization) by canonical discriminant function analysis. The main secondary endpoints were the levels of the 7 biomarkers in the groups with/without AE; comparison of the calculated discriminant score of the biomarkers with traditional logistic regression and C-statistics. The canonical correlation coefficient was 0.642, with a Wilk’s lambda value of 0.78 and p < 0.001. By using the calculated discriminant equation with the weighted mean discriminant score (centroid), the sensitivity and specificity of our model were 79.4% and 74.3% in prediction of AE. These values were higher than that of the calculated C-statistics if traditional risk factors with/without biomarkers were used for AE prediction. In conclusion, canonical discriminant analysis of the multimarker approach is able to define the risk threshold at the individual patient level for personalized medicine.

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Zagidullin, Naufal, Lukas J. Motloch, Diana Gareeva, Aysilu Hamitova, Irina Lakman, Ilja Krioni, Denis Popov, et al. "Combining Novel Biomarkers for Risk Stratification of Two-Year Cardiovascular Mortality in Patients with ST-Elevation Myocardial Infarction." Journal of Clinical Medicine 9, no. 2 (February 18, 2020): 550. http://dx.doi.org/10.3390/jcm9020550.

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ST-elevation myocardial infarction (STEMI) is one of the main reasons for morbidity and mortality worldwide. In addition to the classic biomarker NT-proBNP, new biomarkers like ST2 and Pentraxin-3 (Ptx-3) have emerged as potential tools in stratifying risk in cardiac patients. Indeed, multimarker approaches to estimate prognosis of STEMI patients have been proposed and their potential clinical impact requires investigation. In our study, in 147 patients with STEMI, NT-proBNP as well as serum levels of ST2 and Ptx-3 were evaluated. During two-year follow-up (FU; 734.2 ± 61.2 d) results were correlated with risk for cardiovascular mortality (CV-mortality). NT-proBNP (HR = 1.64, 95% CI = 1.21–2.21, p = 0.001) but also ST2 (HR = 1.000022, 95% CI = 1.00–1.001, p < 0.001) were shown to be reliable predictors of CV-mortality, while the highest predictive power was observed with Ptx-3 (HR = 3.1, 95% CI = 1.63–5.39, p < 0.001). When two biomarkers were combined in a multivariate Cox regression model, relevant improvement of risk assessment was only observed with NT-proBNP+Ptx-3 (AIC = 209, BIC = 214, p = 0.001, MER = 0.75, MEV = 0.64). However, the highest accuracy was seen using a three-marker approach (NT-proBNP + ST2 + Ptx-3: AIC = 208, BIC = 214, p < 0.001, MER = 0.77, MEV = 0.66). In conclusion, after STEMI, ST2 and Ptx-3 in addition to NT-proBNP were associated with the incidence of CV-mortality, with multimarker approaches enhancing the accuracy of prediction of CV-mortality.

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Protasov, V. N., O. Yu Narusov, A. A. Skvortsov, D. E. Protasova, T. V. Kuznetsova, A. A. Petrukhina, V. P. Masenko, and S. N. Tereshchenko. "Multimarker Approach in Risk Stratification of Patients with Decompensated Heart Failure." Kardiologiia 59, no. 1S (January 31, 2019): 53–64. http://dx.doi.org/10.18087/cardio.2637.

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Purpose: to study prognostic value of various biomarkers and their combinations in patients who survived decompensation of chronic heart failure.Materials and methods.Patients (n=159) who were hospitalized with diagnosis of heart failure (HF) decompensation were included in a prospective single-center study. Examination on admission and the day of hospital discharge, included measurement of concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), copeptin, soluble suppression of tumorigenicity 2 (sST2), kopetin, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3. Te combined primary endpoint comprised cardiovascular (CV) death, frst hospitalization because of HF heart failure decompensation, episodes of HF deterioration which required additional i/v diuretics, and CV death with successful resuscitation.Results.During one-year follow-up 56 pts (35.2%) reached the combined primary endpoint. Tere were 78 (49.1%) cardiovascular events. During hospitalization, patients with the decompensation of heart failure experienced a decrease of sST2, NT-proBNP, galectin-3, kopetin, hsTnT and an insignifcant increase of NGAL. ROC analysis identifed signifcant relation between concentrations of NT-proBNP, sST2, copeptin and, to a lesser degree, hsTnT, determined at hospital discharge, and risk of combined primary endpoint during 1-year follow-up: area under the curve (AUC) was 0.733 [95% CI 0.645–0.820], p<0.0001, 0.772 [95% CI 0.688–0.856], p<0.0001, 0.735 [95% CI 0.640–0.830], p<0.0001, and 0.659 [95% CI 0.553–0.764], p=0.005, respectively. Patients who during hospitalization did not achieve cut-oﬀ values of NT-proBNP ≤1696 rg/ml, sST2≤37.8 hg/ml, copeptin≤28.31 rmol/L and hsTnT≤28.37 rg/ml, had higher risk of reaching adverse events during 1 year; OR and 95% CI were 2.96 [1.61, 5.42] p<0.0001, 4.31 [2.34, 7.93] p<0.0001, 3.06 [1.59, 5.89] and 2.19 [2.12, 4.27]), respectively. According to Cox regression analysis, risk of the combined primary end point was the highest in patients with 3 or more elevated markers (OR = 6.6 [3.584, 12.158], p<0.0001), average in patients with 2 elevated markers (OR = 1.123 [0.51, 2.48]), p=0.7), and the lowest in patients with no markers increase or increase of only one marker (OR = 0.11 [0.049, 0.241], p<0.0001). In the Kaplan-Mayer survival analysis all three groups were statistically diﬀerent. In order to identify the most prognostically strong model, a reclassifcation analysis was performed. According to this analysis, the combination of sST2 and NT-proBNP concentrations determined at hospital discharge, exceeded one NT-proBNP (reclassifcation = –8.1%). At the same time, predictive value of only sST2 just insignifcantly less than value of sST2 and NT-proBNP combination (reclassifcation = –1.9%).Conclusion.Patients with three and more elevated markers at hospital discharge have high risk of adverse events. Te biggest prognostic value has combination of sST2 and NT-proBNP concentrations. In order to determine the long-term prognosis of a patient with HF decompensation, it is sufcient to measure concentrations of sST2 and NT-proBNP at hospital discharge. Alternatively, it is possible to limit to sST2 only, which is just insignifcantly inferior to the sST2 and NT-proBNP combination. Patients with concentrations of sST2 ≥37.8 hg/ml and NT-proBNP ≥1696 rg/ml at hospital discharge have maximal 1year risk of death due to recurrent HF decompensation.

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Wettersten, Nicholas, and Alan Maisel. "Role of Cardiac Troponin Levels in Acute Heart Failure." Cardiac Failure Review 1, no. 2 (2015): 102. http://dx.doi.org/10.15420/cfr.2015.1.2.102.

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Cardiac troponin (cTn) is the primary biomarker for the diagnosis of myocardial necrosis in an acute coronary syndrome (ACS). cTn levels can also be elevated in many other conditions, including heart failure, with significant prognostic value. An elevated cTn level can be found in both acute and chronic heart failure and its presence is believed to be due to multiple different pathophysiological processes. In acute decompensated heart failure (AHF), an elevated cTn level has been repeatedly shown to correlate with increased short- and long-term mortality and, to a lesser extent, readmission rates. These associations have been demonstrated with both I and T isoforms of cTn, as well as when troponin is measured with conventional assays or new high-sense assays. In multimarker models, cTn has repeatedly been found to be an independent predictive variable enhancing prognostic ability of the model. cTn is therefore an important biomarker for prognosis in AHF.

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Larina, V. N., and V. I. Lunev. "The Value of Biomarkers in the Diagnosis and Prognosis of Heart Failure in Older Age." Russian Archives of Internal Medicine 11, no. 2 (March 30, 2021): 98–110. http://dx.doi.org/10.20514/2226-6704-2021-11-2-98-110.

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The search for reliable algorithms for diagnosing heart failure with preserved left ventricular ejection fraction (LVEF) in elderly patients is an urgent problem due to the low specificity of clinical manifestations and the peculiarities of involutive processes occurring in the human body. As an alternative diagnostic approach, it is possible to determine in the blood laboratory biochemical markers — a promising method of diagnosis, prognosis and control of the effectiveness of treatment. The article examines the significance of myocardial stress markers (brain natriuretic peptide, N-terminal brain natriuretic peptide, median fragment of atrial natriuretic peptide); «mechanical» myocardial stress (soluble stimulating growth factor expressed by gene 2 — sST2), copeptin, galectin-3 in patients with heart failure and preserved LVEF, including older persons, as well as the possibility of their use in outpatient practice to predict the course of heart failure. The contribution of the multimarker model for a comprehensive assessment of prognosis is discussed, taking into account both the «hemodynamic» side of myocardial stress (pressure or volume overload, markers — natriuretic peptides), and «mechanical» (fibrosis / hypertrophy / heart remodeling, marker — sST2) myocardial changes.

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Matsui, Masaru, Ken-ichi Samejima, Yukiji Takeda, Kaoru Tanabe, Katsuhiko Morimoto, Keisuke Okamoto, Miho Tagawa, et al. "Prognostic Impact of Placental Growth Factor on Mortality and Cardiovascular Events in Dialysis Patients." American Journal of Nephrology 42, no. 2 (2015): 117–25. http://dx.doi.org/10.1159/000439187.

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Background: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis. Methods: We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients. Results: During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95-2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF. Conclusion: PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis.

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Urdea, Mickey, Janice Kolberg, Judith Wilber, Robert Gerwien, Edward Moler, Michael Rowe, Paul Jorgensen, et al. "Validation of a Multimarker Model for Assessing Risk of Type 2 Diabetes from a Five-Year Prospective Study of 6784 Danish People (Inter99)." Journal of Diabetes Science and Technology 3, no. 4 (July 2009): 748–55. http://dx.doi.org/10.1177/193229680900300422.

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Zuliani, Giovanni, Angelina Passaro, Cristina Bosi, Juana Maria Sanz, Alessandro Trentini, Carlo M. Bergamini, Davide Seripa, et al. "Testing a Combination of Markers of Systemic Redox Status as a Possible Tool for the Diagnosis of Late Onset Alzheimer’s Disease." Disease Markers 2018 (September 9, 2018): 1–9. http://dx.doi.org/10.1155/2018/2576026.

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Background. Blood-based parameters reflecting systemic abnormalities associated with typical brain physiopathological hallmarks could be a satisfactory answer to the need of less costly/intrusive and widely available biomarkers for late onset Alzheimer’s disease (LOAD). Cumulating evidence from ourselves and others suggests that systemic oxidative stress (OxS) is precociously associated with LOAD. On this basis, we aimed to identify a combination of markers of redox status that could aid the diagnosis of LOAD.Methods. We reexamined and crossed previous data on 9 serum markers of OxS obtained in a cohort includingn=84controls andn=90LOAD patients by multivariate logistic regression analyses.Results. A multimarker panel was identified that included significantly increased (hydroperoxides and uric acid) and decreased (thiols, residual antioxidant power, and arylesterase activity) markers. The multivariate model yielded an area under receiver-operating characteristic curve (AUC) of 0.808 for the discrimination between controls and LOAD patients, with specificity and sensitivity of 64% and 79%, respectively.Conclusions. This study identified a panel of serum markers that distinguish individuals with LOAD from cognitively healthy control subjects. Replication studies on a larger independent cohort are required to confirm and extend our data.

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Ardigo, Diego, Themistocles L. Assimes, Stephen P. Fortmann, Alan S. Go, Mark Hlatky, Evangelos Hytopoulos, Carlos Iribarren, Philip S. Tsao, Raymond Tabibiazar, and Thomas Quertermous. "Circulating chemokines accurately identify individuals with clinically significant atherosclerotic heart disease." Physiological Genomics 31, no. 3 (November 2007): 402–9. http://dx.doi.org/10.1152/physiolgenomics.00104.2007.

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Serum inflammatory markers correlate with outcome and response to therapy in subjects with cardiovascular disease. However, current individual markers lack specificity for the diagnosis of coronary artery disease (CAD). We hypothesize that a multimarker proteomic approach measuring serum levels of vascular derived inflammatory biomarkers could reveal a “signature of disease” that can serve as a highly accurate method to assess for the presence of coronary atherosclerosis. We simultaneously measured serum levels of seven chemokines [CXCL10 (IP-10), CCL11 (eotaxin), CCL3 (MIP1α), CCL2 (MCP1), CCL8 (MCP2), CCL7 (MCP3), and CCL13 (MCP4)] in 48 subjects with clinically significant CAD (“cases”) and 44 controls from the ADVANCE Study. We applied three classification algorithms to identify the combination of variables that would best predict case-control status and assessed the diagnostic performance of these models with receiver operating characteristic (ROC) curves. The serum levels of six chemokines were significantly higher in cases compared with controls ( P < 0.05). All three classification algorithms entered three chemokines in their final model, and only logistic regression selected clinical variables. Logistic regression produced the highest ROC of the three algorithms (AUC = 0.95; SE = 0.03), which was markedly better than the AUC for the logistic regression model of traditional risk factors of CAD without (AUC = 0.67; SE = 0.06) or with CRP (AUC = 0.68; SE = 0.06). A combination of serum levels of multiple chemokines identifies subjects with clinically significant atherosclerotic heart disease with a very high degree of accuracy. These results need to be replicated in larger cross-sectional studies and their prognostic value explored.

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Oemrawsingh, Rohit M., Timo Lenderink, K. Martijn Akkerhuis, Christopher Heeschen, Stephan Baldus, Stephan Fichtlscherer, Christian W. Hamm, Maarten L. Simoons, and Eric Boersma. "MULTIMARKER RISK MODEL CONTAINING TROPONIN, INTERLEUKIN-10, MYELOPEROXIDASE AND PLACENTAL GROWTH FACTOR PREDICTS LONG-TERM CARDIOVASCULAR RISK AFTER NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME." Journal of the American College of Cardiology 55, no. 10 (March 2010): A97.E917. http://dx.doi.org/10.1016/s0735-1097(10)60918-7.

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Parker, Devin M., Allen D. Everett, Meagan E. Stabler, JoAnna Leyenaar, Luca Vricella, Jeffrey P. Jacobs, Heather Thiessen-Philbrook, Chirag Parikh, Jason Greenberg, and Jeremiah R. Brown PhD. "The Association Between Cardiac Biomarker NT-proBNP and 30-Day Readmission or Mortality After Pediatric Congenital Heart Surgery." World Journal for Pediatric and Congenital Heart Surgery 10, no. 4 (July 2019): 446–53. http://dx.doi.org/10.1177/2150135119842864.

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Background: Very little is known about clinical and biomarker predictors of readmissions following pediatric congenital heart surgery. The cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) can help predict readmission in adult populations, but the estimated utility in predicting risk of readmission or mortality after pediatric congenital heart surgery has not previously been studied. Our objective was to evaluate the association between pre- and postoperative serum biomarker levels and 30-day readmission or mortality for pediatric patients undergoing congenital heart surgery. Methods: We measured pre- and postoperative NT-proBNP levels in two prospective cohorts of 522 pediatric patients <18 years of age who underwent at least one congenital heart operation from 2010 to 2014. Blood samples were collected before and after surgery. We evaluated the association between pre- and postoperative NT-proBNP with readmission or mortality within 30 days of discharge, using multivariate logistic regression, adjusting for covariates based on the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Mortality Risk Model. Results: The Johns Hopkins Children's Center cohort and the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) cohort demonstrate event rates of 12.9% and 9.4%, respectively, for the composite end point. After adjustment for covariates in the STS congenital risk model, we did not find an association between elevated levels of NT-proBNP and increased risk of readmission or mortality following congenital heart surgery for either cohort. Conclusions: In our two cohorts, preoperative and postoperative values of NT-proBNP were not significantly associated with readmission or mortality following pediatric congenital heart surgery. These findings will inform future studies evaluating multimarker risk assessment models in the pediatric population.

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Swiatly, Agata, Agnieszka Horala, Jan Matysiak, Joanna Hajduk, Ewa Nowak-Markwitz, and Zenon Kokot. "Understanding Ovarian Cancer: iTRAQ-Based Proteomics for Biomarker Discovery." International Journal of Molecular Sciences 19, no. 8 (July 31, 2018): 2240. http://dx.doi.org/10.3390/ijms19082240.

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Despite many years of studies, ovarian cancer remains one of the top ten cancers worldwide. Its high mortality rate is mainly due to lack of sufficient diagnostic methods. For this reason, our research focused on the identification of blood markers whose appearance would precede the clinical manifestation of the disease. ITRAQ-tagging (isobaric Tags for Relative and Absolute Quantification) coupled with mass spectrometry technology was applied. Three groups of samples derived from patients with: ovarian cancer, benign ovarian tumor, and healthy controls, were examined. Mass spectrometry analysis allowed for highlighting the dysregulation of several proteins associated with ovarian cancer. Further validation of the obtained results indicated that five proteins (Serotransferrin, Amyloid A1, Hemopexin, C-reactive protein, Albumin) were differentially expressed in ovarian cancer group. Interestingly, the addition of Albumin, Serotransferrin, and Amyloid A1 to CA125 (cancer antigen 125) and HE4 (human epididymis protein4) improved the diagnostic performance of the model discriminating between benign and malignant tumors. Identified proteins shed light on the molecular signaling pathways that are associated with ovarian cancer development and should be further investigated in future studies. Our findings indicate five proteins with a strong potential to use in a multimarker test for screening and detection of ovarian cancer.

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Oemrawsingh, R. M., T. Lenderink, K. M. Akkerhuis, C. Heeschen, S. Baldus, S. Fichtlscherer, C. W. Hamm, M. L. Simoons, and E. Boersma. "Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome." Heart 97, no. 13 (May 10, 2011): 1061–66. http://dx.doi.org/10.1136/hrt.2010.197392.

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Klisic, Aleksandra, Aleksandra Isakovic, Gordana Kocic, Nebojsa Kavaric, Milovan Jovanovic, Elvir Zvrko, Verica Skerovic, and Ana Ninic. "Relationship between Oxidative Stress, Inflammation and Dyslipidemia with Fatty Liver Index in Patients with Type 2 Diabetes Mellitus." Experimental and Clinical Endocrinology & Diabetes 126, no. 06 (September 11, 2017): 371–78. http://dx.doi.org/10.1055/s-0043-118667.

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Abstract Introduction/Aim Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in individuals with type 2 diabetes mellitus (DM2), we aimed to investigate the potential benefit of determining markers of oxidative stress, inflammation and dyslipidemia for prediction of NAFLD, as estimated with fatty liver index (FLI) in individuals with DM2. Methods A total of 139 individuals with DM2 (of them 49.9% females) were enrolled in cross-sectional study. Anthropometric and biochemical parameters, as well as blood pressure were obtained. A FLI was calculated. Results Multivariate logistic regression analysis showed that high density lipoprotein cholesterol (HDL-c) and malondialdehyde (MDA) were independent predictors of higher FLI [Odds ratio (OR)=0.056, p=0.029; and OR=1.105, p=0.016, respectively]. In Receiver Operating Characteristic curve analysis, the addition of fatty liver risk factors (e. g., age, gender, body height, smoking status, diabetes duration and drugs metabolized in liver) to each analysed biochemical parameter [HDL-c, non-HDL-c, high sensitivity C-reactive protein (hsCRP), MDA and advanced oxidant protein products (AOPP)] in Model 1, increased the ability to discriminate patients with and without fatty liver [Area under the curve (AUC)=0.832, AUC=0.808, AUC=0.798, AUC=0.824 and AUC=0.743, respectively]. Model 2 (which included all five examined predictors, e. g., HDL-c, non-HDL-c, hsCRP, MDA, AOPP, and fatty liver risk factors) improved discriminative abilities for fatty liver status (AUC=0.909). Even more, Model 2 had the highest sensitivity and specificity (89.3% and 87.5%, respectively) together than each predictor in Model 1. Conclusion Multimarker approach, including biomarkers of oxidative stress, dyslipidemia and inflammation, could be of benefit in identifying patients with diabetes being at high risk of fatty liver disease.

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Zelniker, Thomas A., Sebastian Spaich, Jan Stiepak, Florian Steger, Hugo A. Katus, and Michael R. Preusch. "Serum neprilysin and the risk of death in patients with out-of-hospital cardiac arrest of non-traumatic origin." European Heart Journal: Acute Cardiovascular Care 9, no. 4_suppl (November 19, 2018): S169—S174. http://dx.doi.org/10.1177/2048872618815062.

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Background: Early risk stratification remains an unmet clinical need in patients with in out-of-hospital cardiac arrest. We hypothesised that soluble neprilysin may represent a promising biomarker in patients with out-of-hospital cardiac arrest of non-traumatic origin and provide new pathobiological insight. Methods: This pilot study was a biomarker analysis from the Heidelberg Resuscitation Registry. Serum soluble neprilysin levels on admission were measured in 144 patients with successful return of spontaneous circulation after out-of-hospital cardiac arrest of non-traumatic origin. The primary endpoint was time to all-cause mortality. KM Event Rates are reported. Cox models were adjusted for age, bystander resuscitation, initial ECG rhythm, baseline estimated glomerular filtration rate, baseline lactate, left ventricular function at baseline, and targeted temperature management. Results: In total, 90 (62.5%) patients died over a follow-up of at least 30 days. Soluble neprilysin correlated weakly with high-sensitivity troponin T ( r=0.18, P=0.032) but did not correlate significantly with estimated glomerular filtration rate ( r=−0.12) or lactate ( r=0.11). Patients with elevated soluble neprilysin levels on admission were at significantly higher risk of all-cause mortality (Q4 69.1% vs. Q1 48.4%). After multivariable adjustment, soluble neprilysin in the top quartile (Q4) was significantly associated with all-cause mortality (Q4 vs. Q1: adjusted hazard ratio 2.48 (1.20–5.12)). In an adjusted multimarker model including high-sensitivity troponin T and high-sensitivity C-reactive protein, soluble neprilysin and high-sensitivity troponin T remained independently associated with all-cause mortality (soluble neprilysin: adjusted hazard ratio 2.27 (1.08–4.78); high-sensitivity troponin T: adjusted hazard ratio 3.40 (1.63–7.09)). Conclusion: Soluble neprilysin, measured as early as on hospital admission, was independently associated with all-cause mortality in patients with out-of-hospital cardiac arrest of non-traumatic origin and may prove to be useful in the estimation of risk in these patients.

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Patoulias, Dimitrios, Konstantinos Stavropoulos, Konstantinos Imprialos, Vasilios Athyros, Haris Grassos, Michael Doumas, and Charles Faselis. "Inflammatory Markers in Cardiovascular Disease; Lessons Learned and Future Perspectives." Current Vascular Pharmacology 19, no. 3 (December 31, 2020): 323–42. http://dx.doi.org/10.2174/1570161118666200318104434.

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Background: Cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality worldwide. It is now established that inflammation plays a crucial role in atherosclerosis and atherothrombosis, and thus, it is closely linked to cardiovascular disease. Objective: The aim of the present review is to summarize and critically appraise the most relevant evidence regarding the potential use of inflammatory markers in the field of CVD. Method: We conducted a comprehensive research of the relevant literature, searching MEDLINE from its inception until November 2018, primarily for meta-analyses, randomized controlled trials and observational studies. Results: Established markers of inflammation, mainly C-reactive protein, have yielded significant results both for primary and secondary prevention of CVD. Newer markers, such as lipoprotein-associated phospholipase A2, lectin-like oxidized low-density lipoprotein receptor-1, cytokines, myeloperoxidase, cell adhesion molecules, matrix metalloproteinases, and the CD40/CD40 ligand system, have been largely evaluated in human studies, enrolling both individuals from the general population and patients with established CVD. Some markers have yielded conflicting results; however, others are now recognized not only as promising biomarkers of CVD, but also as potential therapeutic targets, establishing the role of anti-inflammatory and pleiotropic drugs in CVD. Conclusion: There is significant evidence regarding the role of consolidated and novel inflammatory markers in the field of diagnosis and prognosis of CVD. However, multimarker model assessment, validation of cut-off values and cost-effectiveness analyses are required in order for those markers to be integrated into daily clinical practice.

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Koyanagi, Kazuo, Steven J. O'Day, Rene Gonzalez, Karl Lewis, William A. Robinson, Thomas T. Amatruda, He-Jing Wang, et al. "Serial Monitoring of Circulating Melanoma Cells During Neoadjuvant Biochemotherapy for Stage III Melanoma: Outcome Prediction in a Multicenter Trial." Journal of Clinical Oncology 23, no. 31 (November 1, 2005): 8057–64. http://dx.doi.org/10.1200/jco.2005.02.0958.

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PurposeCirculating tumor cells (CTCs) in blood may be important in assessing tumor progression and treatment response. We hypothesized that quantitative real-time reverse transcriptase polymerase chain reaction using multimarker mRNA assays could detect CTCs and be used as a surrogate predictor of outcome in patients receiving neoadjuvant biochemotherapy (BC) for melanoma.Patients and MethodsBlood specimens were collected at four sampling points from 63 patients enrolled on a prospective multicenter phase II trial of BC before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. Each specimen was assessed by quantitative real-time reverse transcriptase polymerase chain reaction for expression of four melanoma-associated markers: melanoma antigen recognized by T cells 1; β1 → 4-N-acetylgalactosaminyltransferase; paired box homeotic gene transcription factor 3; and melanoma antigen gene-A3 family, and the changes of CTCs during treatment and prognostic effect of CTCs after overall treatment on recurrence and survival were investigated.ResultsAt a median postoperative follow-up time of 30.4 months, 44 (70%) patients were clinically disease free. In relapse-free patients, the number of detected markers significantly decreased during preoperative BC (P = .036), during postoperative BC (P = .002), and during overall treatment (P < .0001). Marker detection after overall treatment was associated with significant decreases in relapse-free and overall survival (P < .0001). By multivariate analysis using a Cox proportional-hazards model, the number of markers detected after overall treatment was a significant independent prognostic factor for overall survival (risk ratio, 12.6; 95% CI, 3.16 to 50.5; P = .0003).ConclusionSerial monitoring of CTCs in blood may be useful for indicating systemic subclinical disease and predicting outcome of patients receiving neoadjuvant BC for metastatic melanoma.

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Zelniker, Thomas A., David A. Morrow, Ofri Mosenzon, Yared Gurmu, Kyungah Im, Avivit Cahn, Itamar Raz, et al. "Cardiac and Inflammatory Biomarkers Are Associated with Worsening Renal Outcomes in Patients with Type 2 Diabetes Mellitus: Observations from SAVOR-TIMI 53." Clinical Chemistry 65, no. 6 (June 1, 2019): 781–90. http://dx.doi.org/10.1373/clinchem.2018.298489.

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Abstract BACKGROUND Cardiac and renal diseases commonly occur with bidirectional interactions. We hypothesized that cardiac and inflammatory biomarkers may assist in identification of patients with type 2 diabetes mellitus (T2DM) at high risk of worsening renal function. METHODS In this exploratory analysis from SAVOR-TIMI 53, concentrations of high-sensitivity cardiac troponin T (hs-TnT), N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) were measured in baseline serum samples of 12310 patients. The primary end point for this analysis was a ≥40% decrease in estimated glomerular filtration rate (eGFR) at end of treatment (EOT) at a median of 2.1 years. The relationships between biomarkers and the end point were modeled using adjusted logistic and Cox regression. RESULTS After multivariable adjustment including baseline renal function, each biomarker was independently associated with an increased risk of ≥40% decrease in eGFR at EOT [Quartile (Q) Q4 vs Q1: hs-TnT adjusted odds ratio (OR), 5.63 (3.49–9.10); NT-proBNP adjusted OR, 3.53 (2.29–5.45); hs-CRP adjusted OR, 1.84 (95% CI, 1.27–2.68); all P values ≤0.001]. Furthermore, each biomarker was independently associated with higher risk of worsening of urinary albumin-to-creatinine ratio (UACR) category (all P values ≤0.002). Sensitivity analyses in patients without heart failure and eGFR >60 mL/min provided similar results. In an adjusted multimarker model, hs-TnT and NT-proBNP remained significantly associated with both renal outcomes (all P values <0.01). CONCLUSIONS hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM. Patients with high cardiac or inflammatory biomarkers should be treated not only for their risk of cardiovascular outcomes but also followed for renal deterioration.

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Fleming, Jessica L., Stephanie L. Pugh, Barbara J. Fisher, Glenn J. Lesser, David R. Macdonald, Erica H. Bell, Joseph P. McElroy, et al. "Long-Term Report of a Comprehensive Molecular and Genomic Analysis in NRG Oncology/RTOG 0424: A Phase II Study of Radiation and Temozolomide in High-Risk Grade II Glioma." JCO Precision Oncology, no. 5 (August 2021): 1397–407. http://dx.doi.org/10.1200/po.21.00112.

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PURPOSE This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including MGMT promoter methylation and mutations in ATRX, CIC, FUBP1, TERT, and TP53, in NRG/RTOG 0424 using long-term follow-up data. METHODS Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and MGMT promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics. RESULTS We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were IDHmutant/co-deleted, 28 (35%) were IDHmutant/non-co-deleted, and 26 (32.5%) were IDHwild-type. Upon single-marker MVA, both IDHmutant subgroups were associated with significantly better OS and PFS ( P values < .001), compared with the IDHwild-type subgroup. MGMT promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that MGMT promoter methylation was statistically significant for OS ( P value < .001) and PFS ( P value = .003). In a multimarker MVA, one WHO subgroup comparison ( IDHmutant/co-deleted v IDHwild-type) was significant for OS ( P value = .045), whereas MGMT methylation did not retain significance. CONCLUSION This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status.

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Ikonomidis, Ignatios, Christos A. Michalakeas, John Lekakis, Ioannis Paraskevaidis, and Dimitrios Th. Kremastinos. "Multimarker Approach in Cardiovascular Risk Prediction." Disease Markers 26, no. 5-6 (2009): 273–85. http://dx.doi.org/10.1155/2009/135423.

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Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, such as inflammation, oxidative stress, myocardial injury, activation of the neurohormonal pathways, myocardial stress and renal function. Current thinking supports the notion that the combination of these biomarkers could increase their diagnostic and prognostic value. The multimarker approach offers benefits since it increases the diagnostic and prognostic information and may help in the design of a strategy for prevention or management of cardiovascular diseases. The purpose of the current review is to describe the characteristics of promising biomarkers which have shown an important additive value in the assessment of cardiovascular risk. Also, an extended reference is made regarding studies that address the prognostic value of multimarker models in the settings of primary prevention of cardiovascular disease and secondary prevention for patients with acute coronary syndromes, chronic coronary artery disease and heart failure.

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Salanie, Bernard. "Wage and price adjustment in a multimarket disequilibrium model." Journal of Applied Econometrics 6, no. 1 (January 1991): 1–15. http://dx.doi.org/10.1002/jae.3950060102.

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Whitwell, Harry J., Jenny Worthington, Oleg Blyuss, Aleksandra Gentry-Maharaj, Andy Ryan, Richard Gunu, Jatinderpal Kalsi, et al. "Improved early detection of ovarian cancer using longitudinal multimarker models." British Journal of Cancer 122, no. 6 (January 15, 2020): 847–56. http://dx.doi.org/10.1038/s41416-019-0718-9.

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Brännlund, Runar, and Bengt Kriström. "Welfare Measurement in Single and Multimarket Models: Theory and Application." American Journal of Agricultural Economics 78, no. 1 (February 1996): 157–65. http://dx.doi.org/10.2307/1243787.

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Ponce, Roberto, María Blanco, and Carlo Giupponi. "Welfare Effects of Water Variability in Agriculture. Insights from a Multimarket Model." Water 7, no. 12 (June 16, 2015): 2908–23. http://dx.doi.org/10.3390/w7062908.

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Will, Thomas E. "A multilevel model of multimarket contact: competence depletion and punctuated forbearance hypotheses." Organization Management Journal 8, no. 2 (June 2011): 88–104. http://dx.doi.org/10.1057/omj.2011.13.

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Hou, Wolin, Xiyan Meng, Aihua Zhao, Weijing Zhao, Jiemin Pan, Junling Tang, Yajuan Huang, et al. "Development of Multimarker Diagnostic Models from Metabolomics Analysis for Gestational Diabetes Mellitus (GDM)." Molecular & Cellular Proteomics 17, no. 3 (December 27, 2017): 431–41. http://dx.doi.org/10.1074/mcp.ra117.000121.

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Maestri, Cláudia Olímpia Neves Mamede, and Rodrigo Fernandes Malaquias. "Aspects of manager, portfolio allocation, and fund performance in Brazil." Revista Contabilidade & Finanças 29, no. 76 (April 2018): 82–96. http://dx.doi.org/10.1590/1808-057x201804590.

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ABSTRACT This paper intends to contribute to the literature on investment funds in emerging markets by looking at the performance of multimarket funds in Brazil from a manager perspective. The aim of the paper was to analyze whether some characteristics of investment fund managers, as well as their portfolio holdings, can affect fund performance. In emerging countries both portfolio asset allocation and manager characteristics can help explain differences in the fund performance, which increases the relevance of this study. Therefore, the impact of this research lies in its revealing a significant relationship between risk-adjusted return and the portion of portfolios allocated to fixed or variable income, which seems that have not been explored in the context of emerging economies yet. A total of 6,002 multimarket funds were analyzed, covering the period between September 2009 and December 2015, using panel data with robust standard errors clustered by funds. We also employed robust statistics in order to assess some potential biases due to outliers, by analyzing the breakdown point in the estimated models. It should be noted that portfolio composition (allocation of portfolios into variable income and fixed income) was the most important factor in explaining a potential change in the performance of Brazilian multimarket funds. Also important were the effectiveness of the management of these funds, that is, the best risk-adjusted returns were delivered by less experienced managers, funds investing more in fixed income, managers with more funds under management, and larger funds.

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Wang, Xingyuan, Fuan Li, and Fan Jia. "Optimal Advertising Budget Allocation across Markets with Different Goals and Various Constraints." Complexity 2020 (May 21, 2020): 1–12. http://dx.doi.org/10.1155/2020/6162056.

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Advertising budget allocation across multiple markets has drawn considerable attention in recent years. To expand previous research and fill a gap in the current literature, this study proposes two decision models for optimal budget allocation decisions across multimarkets with different goals and various constraints. In addition to the market parameters proposed by the Vidale–Wolfe model, the present study incorporates market goals and advertising objectives into budget allocation decisions. Different types of markets are defined in terms of the goal set for market share or profit. Given the characteristics of different markets, two separate decision models are developed. Model I aims to maximize sales volume given a fixed advertising budget, while model II seeks to minimize the advertising budget given a total of targeted sales volume for all the markets. Solutions to the two models are discussed, and a numerical example is provided to demonstrate how to apply the models in making budget allocation decision.

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Willett, K., and R. Sharda. "A Dynamic Multimarket Equilibrium Model for the Economic Analysis of Pollution Control Policies." Environment and Planning A: Economy and Space 20, no. 3 (March 1988): 391–405. http://dx.doi.org/10.1068/a200391.

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The subject of this paper is the development of a dynamic economy-wide market equilibrium model that can be used to assess impacts of pollution control policies on economic performance. The model is stated in a mathematical programming structure with pollution discharge relationships and investment activities. A complete specification of the model is presented. Some equilibrium conditions for the model are developed and their implications for policy purposes are discussed. The paper also contains comments on a possible solution procedure for such a model.

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Moreira, Patrycia Olivo, Vitor Borges Tavares, and Rodrigo Fernandes Malaquias. "Performance e Foco do Gestor em Fundos Multimercados." RACE - Revista de Administração, Contabilidade e Economia 16, no. 2 (August 30, 2017): 633–54. http://dx.doi.org/10.18593/race.v16i2.12250.

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Resumo O objetivo principal com este artigo foi analisar a relação entre o foco do gestor e a performance dos fundos de investimentos multimercados. Com base em estudos anteriores, o modelo de pesquisa também considerou o foco da família administradora. A base de dados foi composta por 2.942 fundos no período de janeiro de 2012 a dezembro de 2015. Observou-se que o foco da família de fundos apresentou relação positiva com o desempenho, assim como o foco do gestor em fundos multimercados; porém, essa relação não foi persistente para diferentes medidas de performance como variável dependente. Com base nesses resultados, evidenciaram-se, nesta pesquisa, variáveis que podem ser utilizadas por cotistas de fundos de investimentos para a alocação de seus recursos no mercado financeiro.Palavras-chave: Investidores institucionais. Gestão ativa. Economia de escala. Abstract The aim of this research is to analyze the relationship between managers’ focus and the performance of multimarket investment funds. Grounded in previous research, the quantitative model of this study also involves the focus of funds families. The database is comprised of 2,942 investment funds in the period from january 2012 to december 2015. We observed that both managers’ focus and families’ focus in the category of multimarket funds have a positive effect on the performance of investment funds. Nevertheless, the positive effect of these variables is not consistent among different indexes of performance. Based on these results, this research discloses some variables that investors can use in order to allocate their financial resources in the capital market.Keywords: Institutional investors. Active management. Economies of scale.

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Diao, Xinshen, and Daniel B. Sarpong. "Poverty Implications of Agricultural Land Degradation in Ghana: An Economy-wide, Multimarket Model Assessment." African Development Review 23, no. 3 (September 2011): 263–75. http://dx.doi.org/10.1111/j.1467-8268.2011.00285.x.

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Zhao, LiuWei. "Analysis and Control of the Complex Dynamics of a Multimarket Cournot Investment Game with Bounded Rationality." Discrete Dynamics in Nature and Society 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/7342405.

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A dynamic multimarket Cournot model is introduced based on a specific inverse demand function. Puu’s incomplete information approach, as a realistic method, is used to contract the corresponding dynamical model under this function. Therefore, some stability analysis is carried out on the model to detect the stability and instability conditions of the system’s Nash equilibrium. Based on the analysis, some dynamic phenomena such as bifurcation and chaos are found. Numerical simulations are used to provide experimental evidence for the complicated behaviors of the system evolution. It is observed that the equilibrium of the system can lose stability via flip bifurcation or Neimark-Sacker bifurcation and time-delayed feedback control is used to stabilize the chaotic behaviors of the system.

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Ratnik, Kaspar, Kristiina Rull, Ele Hanson, Kalle Kisand, and Maris Laan. "Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia." Journal of Applied Laboratory Medicine 5, no. 6 (May 15, 2020): 1156–71. http://dx.doi.org/10.1093/jalm/jfaa054.

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Abstract Background Preeclampsia (PE) affects 2%–8% of all pregnancies worldwide. The predictive value of the currently used maternal serum fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) test is < 40% for PE onset within 4 weeks. We aimed to develop an innovative multiplex assay to improve PE prediction. Methods The 6PLEX assay combining the measurements of ADAM12, sENG, leptin, PlGF, sFlt-1, and PTX3 was developed for the Luminex® xMAP platform. Assay performance was evaluated using 61 serum samples drawn from 53 pregnant women between 180 and 275 gestational days: diagnosed PE cases, n = 4; cases with PE onset within 4–62 days after sampling, n = 25; controls, n = 32. The B·R·A·H·M·S Kryptor sFlt-1/PlGF test (Thermo Fisher Scientific, Hennigsdorf, Germany) was applied as an external reference. Alternative PE prediction formulae combining 6PLEX measurements with clinical parameters were developed. Results There was a high correlation in sFlt-1/PlGF estimated for individual sera between the 6PLEX and B·R·A·H·M·S Kryptor immunoassays (Spearman’s r = 0.93, P < 0.0001). The predictive power of the 6PLEX combined with gestational age and maternal weight at sampling reached AUC 0.99 (95% CI 0.97–1.00) with sensitivity 100.0% and specificity 96.9%. In all models, sFlt-1/PlGF derived from the B·R·A·H·M·S immunoassays exhibited the lowest AUC value (<0.87) and sensitivity (<80%) with broad confidence intervals (13%–92%). The estimated prognostic yield of the 6PLEX compared to the B·R·A·H·M·S assay was significantly higher (96.5% vs 73.7%; P = 0.0005). Conclusions The developed single-tube multimarker assay for PE risk estimation in combination with clinical symptoms reached high prognostic yield (96.5%) and exhibited superior performance compared to the sFlt-1/PlGF test.

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de Moor, Janet S., Stacy W. Gray, Sandra A. Mitchell, Carrie N. Klabunde, and Andrew N. Freedman. "Oncologist Confidence in Genomic Testing and Implications for Using Multimarker Tumor Panel Tests in Practice." JCO Precision Oncology, no. 4 (September 2020): 620–31. http://dx.doi.org/10.1200/po.19.00338.

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PURPOSE The evolution of precision oncology increasingly requires oncologists to incorporate genomic testing into practice. Yet, providers’ confidence with genomic testing is poorly documented. This article describes medical oncologists’ confidence with genomic testing and the association between genomic confidence and test use. METHODS We used data from the 2017 National Survey of Precision Medicine in Cancer Treatment to characterize oncologists’ confidence with genomic testing. Genomic confidence was examined separately by type of test user: next-generation sequencing (NGS) only, gene expression (GE) only, both NGS and GE, or nonuser. Predictors of genomic confidence were examined with multinomial logistic regression. The association between genomic confidence and test use was examined with multivariable linear regression. RESULTS More than 75% of genomic test users were either moderately or very confident about using results from multimarker tumor panel tests to guide patient care. Confidence with using multimarker tumor panel tests was highest among both NGS and GE test users, with 60.1% very confident in using test results, and lowest among NGS-only test users, with 38.2% very confident in using test results. Oncologists were most confident in using single-gene tests and least confident in using whole-genome or -exome sequencing to guide patient care. Genomic confidence was positively associated with self-reported test use. In adjusted models, training in genomics, larger patient volume, and treating patients with solid tumors predicted higher genomic confidence. Onsite pathology services and receipt of electronic medical record alerts for genomic testing predicted lower genomic confidence. CONCLUSION Oncologists’ confidence varies by testing platform, patient volume, genomic training, and practice infrastructure. Research is needed to identify modifiable factors that can be targeted to enhance provider confidence with genomic testing.

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Holt, Matthew T. "A Multimarket Bounded Price Variation Model under Rational Expectations: Corn and Soybeans in the United States." American Journal of Agricultural Economics 74, no. 1 (February 1992): 10–20. http://dx.doi.org/10.2307/1242985.

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Lidonnici, Maria Rosa, Annamaria Aprile, Marta Frittoli, Giacomo Mandelli, Ylenia Paleari, Antonello Spinelli, Bernhard Gentner, et al. "Human CD34+ Cells from Different Sources Disclose a Specific Stemness Signature." Blood 128, no. 22 (December 2, 2016): 4709. http://dx.doi.org/10.1182/blood.v128.22.4709.4709.

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Abstract Over the past decades outcomes of clinical hematopoietic stem cell transplants have established a clear relationship between the sources of hematopoietic stem cells (HSCs) infused and their differential homing and engraftment properties. For a long time, bone marrow (BM) harvest has been the preferred source of hematopoietic stem and progenitor cells (HSPCs) for hematopoietic reconstitution following myeloablative conditioning regimen. At present, mobilized peripheral blood (PB) is commonly used for hematopoietic cells transplantation in both adults and children, particularly in the autologous setting, and it has progressively replaced BM as the source of HSCs.HSCs are maintained in their niche by binding to cellular determinants through adhesion molecules and diverse strategies are currently used to promote their egress from BM to PB. Traditionally, the growth factor granulocyte-colony stimulating factor (G-CSF) represents the gold standard agent to mobilize HSPCs for transplantation. Nevertheless, other compounds have been recently tested. One of the most successful mobilizing agents is Plerixafor (AMD3100, Mozobil™), a bicyclam molecule that selectively and reversibly antagonizes the binding of stromal cell derived factor-1 (SDF-1), located on the surface of BM stromal cells and osteoclasts, to chemokine CXC-receptor-4 (CXCR4), located on the surface of HSPCs, with the subsequent mobilization in the blood. The use of this drug is currently approved by FDA and EMA in combination with G-CSF, in patients affected by lymphoma or multiple myeloma whose cells mobilize poorly with G-CSF alone. Clinical trials demonstrated that Plerixafor alone safely and rapidly mobilizes HSCs also in healthy donors, beta-thalassemia patients and pediatric patients affected by malignancies. Previous characterization studies on non-human primates and human samples of Plerixafor mobilized cells in comparison to cells mobilized by G-CSF alone or in combination with Plerixafor showed a different expression profile, cell composition and engrafting potential in a xenotransplant model. From these studies remains unsolved whether Plerixafor, G-CSF, or their combination mobilizes different primitive HSC populations, defined both by multimarker immunophenotype and in vivo functional analysis. In the present study we investigated by controlled comparative analysis the functional and molecular hallmarks of human HSCs collected from BM, G-CSF and/or Plerixafor mobilized peripheral blood. We show that Plerixafor alone mobilizes preferentially long-term hematopoietic stem cells (LT-HSCs), defined as CD34+CD38/lowCD90+CD45RA-CD49f+ cells and primitive populations of HSCs. These cells possess higher ability to home to hematopoietic niches and engraft in NOD/SCID/IL2rγnull (NSG) mice, resulting in enriched scid-repopulating cell frequency, in comparison to other sources. The higher content of CXCR4+ and CD49f+ cells correlates with this feature. Furthermore, global gene expression profiling highlights the superior in vivo reconstitution activity of Plerixafor mobilized cells. The "stemness" signature of cells dislodged from their niche by the drug is attenuated by the combined use with G-CSF, which emphasizes the gene expression profile induced by G-CSF treatment. These data indicate that a qualitative advantage accounts for the superior performance of Plerixafor mobilized cells. These findings provide the rationale for using a suboptimal dose of more primitive HSCs when target cell number for transplantation is limited, or when G-CSF mobilization is too risky like in sickle cell anemia patients. Moreover, CD34+ cells mobilized by Plerixafor alone or with the combination of G-CSF are efficiently transduced by a lentiviral vector encoding for human ß-globin gene (GLOBE LV) and are able to engraft and differentiate in vivo, supporting their use for gene therapy applications. Disclosures Ciceri: MolMed SpA: Consultancy.

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Sarangi, Subrat, Abhishek Chakraborty, and Konstantinos P. Triantis. "Multimarket competition effects on product line decisions – A multi-objective decision model in fast moving consumer goods industry." Journal of Business Research 133 (September 2021): 388–98. http://dx.doi.org/10.1016/j.jbusres.2021.05.019.

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Li, Gang, Wen Wang, and Hong-Nan Li. "Experiment and Application of Market-Based Control for Engineering Structures." Journal of Applied Mathematics 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/219537.

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An experimental study on the vibration control of a single-degree-of-freedom model is carried out to verify market-based control (MBC) strategy effect. Results show that the MBC strategy can reduce both displacement and acceleration responses. Additionally, the MBC strategy is applied to a long-span bridge considering the travelling wave effect. Numerical simulations indicate that the displacement and acceleration responses of the long-span bridge with the travelling wave effect are smaller than those without, and the larger the velocity of travelling wave is, the better the control effect of MBC is. Based on the MBC theory and multimarket-based control (MMBC) presented here it is further applied to a large-space structure considering multiple dimensional features of structural model and ground motions. It is concluded that the MMBC strategy reduces the displacement response of the large-space structure, especially on vertical displacements, but has limited control effects on accelerations.

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Saenz-Pipaon, Goren, Esther Martinez-Aguilar, Josune Orbe, Arantxa González Miqueo, Leopoldo Fernandez-Alonso, Jose Antonio Paramo, and Carmen Roncal. "The Role of Circulating Biomarkers in Peripheral Arterial Disease." International Journal of Molecular Sciences 22, no. 7 (March 30, 2021): 3601. http://dx.doi.org/10.3390/ijms22073601.

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Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.

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Revoredo-Giha, Cesar, Luiza Toma, and Faical Akaichi. "An Analysis of the Tax Incidence of VAT to Milk in Malawi." Sustainability 12, no. 19 (September 27, 2020): 8003. http://dx.doi.org/10.3390/su12198003.

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Dairy is a key investment sector for the Government of Malawi. On 1 October 2016, the Malawi Revenue Authority announced that milk, which until then had been exempted from value added tax (VAT), was going to be taxed at the standard rate of 16.5 percent. The measure has been met with strong opposition and thus, was short lived (eliminated in May 2017). The purpose of this paper is to present an analysis of the effect that such a tax would have on its incidence, on the different stages of the supply chain, and ultimately on its economic and social sustainability. The paper investigates these implications by developing a multimarket model applied to the Malawian dairy supply chain. The results indicate that 24.3 percent of the VAT revenues would be borne by consumers and the remaining 75.7 percent would be borne by the domestic dairy industry (i.e., processors and smallholder farmers). This was due mainly to the value of the price elasticity of consumers’ demand for pasteurised milk. The results highlight the vulnerability of inclusive value chains to economic policies that may affect consumers’ demand.

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Kalla, R., A. T. Adams, N. T. Ventham, N. A. Kennedy, R. White, C. Clarke, A. Ivens, et al. "Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease." Journal of Crohn's and Colitis 14, no. 12 (June 29, 2020): 1724–33. http://dx.doi.org/10.1093/ecco-jcc/jjaa134.

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Abstract Background MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. Methods In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn’s disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. Results In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20–3.27; logrank p = 1.80 × 10–3), in particular CD [HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. Interpretation We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

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Malaquias, Rodrigo Fernandes, and Dermeval Martins Borges Junior. "Strategy, tax planning and liquidity constraints in investment funds." Journal of Economic Studies 46, no. 4 (August 5, 2019): 842–57. http://dx.doi.org/10.1108/jes-11-2017-0334.

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Purpose The purpose of this paper is to analyze the effect of the interaction between liquidity constraints and tax planning on the performance of Brazilian investment funds, since liquidity constraints reduce precipitated withdrawals, allowing tax planning operationalization. Design/methodology/approach The sample of this study is comprised of 8,008 Brazilian multimarket funds, considering the period from January 2004 to September 2017. The authors considered tax planning, lockup periods and minimum balance of investment as independent variables, and the authors used the Sharpe ratio as a proxy for performance. To test the study hypothesis, the authors employed regression models with panel data. Findings The main findings indicate some evidences that investment funds which implement, at the same time, liquidity constraints with tax planning have an extra risk-adjusted return index. This result can represent a premium registered by investment funds with have enough resources to achieve competitive advantage. Nevertheless, the result for the main hypothesis was not robust to different forms of performance measurement. Originality/value This study promotes an interaction between finance and organizational strategy, since it employs aspects of strategy theories to support the implications that the internal resources of investment funds, such as their liquidity constraints and tax planning, may exert on their performance. In addition, this study advances by providing new evidences about liquidity constraints in investments funds, which have the potential to contribute with the operationalization of strategy and tax planning of funds’ managers.

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Journal articles on the topic 'Multimarker model'

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