Development and validation of immune dysfunction score to predict 28-day mortality of sepsis patients

PubMed Central

Fang, Wen-Feng; Douglas, Ivor S.; Chen, Yu-Mu; Lin, Chiung-Yu; Kao, Hsu-Ching; Fang, Ying-Tang; Huang, Chi-Han; Chang, Ya-Ting; Huang, Kuo-Tung; Wang, Yi-His; Wang, Chin-Chou

2017-01-01

Background Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients’ immune dysfunction status for 28-day mortality prediction. Methods A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated immune dysfunction status through measurement of baseline plasma Cytokine levels, Monocyte human leukocyte-DR expression by flow cytometry, and stimulated immune response using post LPS stimulated cytokine elevation ratio. An immune dysfunction score was created for 28-day mortality prediction and was validated. Results A total of 151 patients were enrolled. Data of the first consecutive 106 septic patients comprised the training cohort, and of other 45 patients comprised the validation cohort. Among the 106 patients, 21 died and 85 were still alive on day 28 after ICU admission. (mortality rate, 19.8%). Independent predictive factors revealed via multivariate logistic regression analysis included segmented neutrophil-to-monocyte ratio, granulocyte-colony stimulating factor, interleukin-10, and monocyte human leukocyte antigen-antigen D–related levels, all of which were selected to construct the score, which predicted 28-day mortality with area under the curve of 0.853 and 0.789 in the training and validation cohorts, respectively. Conclusions The immune dysfunction scoring system developed here included plasma granulocyte-colony stimulating factor level, interleukin-10 level, serum segmented neutrophil-to-monocyte ratio, and monocyte human leukocyte antigen-antigen D–related expression appears valid and reproducible for predicting 28-day mortality. PMID:29073262

DNA-PKcs Expression Is a Predictor of Biochemical Recurrence After Permanent Iodine 125 Interstitial Brachytherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molina, Sarah; Department of Radiation Oncology, CHU/Université de Poitiers, Poitiers; Guerif, Stéphane

Purpose: Predictive factors for biochemical recurrence (BCR) in localized prostate cancer (PCa) after brachytherapy are insufficient to date. Cellular radiosensitivity depends on DNA double-strand breaks, mainly repaired by the nonhomologous end-joining (NHEJ) system. We analyzed whether the expression of NHEJ proteins can predict BCR in patients treated by brachytherapy for localized PCa. Methods and Materials: From 983 PCa cases treated by brachytherapy between March 2000 and March 2012, 167 patients with available biopsy material suitable for in situ analysis were included in the study. The median follow-up time was 47 months. Twenty-nine patients experienced BCR. All slides were reviewed to reassessmore » the Gleason score. Expression of the key NHEJ proteins DNA-PKcs, Ku70, and Ku80, and the proliferation marker Ki67, was studied by immunohistochemistry performed on tissue microarrays. Results: The Gleason scores after review (P=.06) tended to be associated with BCR when compared with the score initially reported (P=.74). Both the clinical stage (P=.02) and the pretreatment prostate-specific antigen level (P=.01) were associated with biochemical failure. Whereas the expression of Ku80 and Ki67 were not predictive of relapse, positive DNA-PKcs nuclear staining (P=.003) and higher Ku70 expression (P=.05) were associated with BCR. On multivariate analysis, among pretreatment variables, only DNA-PKcs (P=.03) and clinical stage (P=.02) remained predictive of recurrence. None of the patients without palpable PCa and negative DNA-PKcs expression experienced biochemical failure, compared with 32% of men with palpable and positive DNA-PKcs staining that recurred. Conclusions: Our results suggest that DNA-PKcs could be a predictive marker of BCR after brachytherapy, and this might be a useful tool for optimizing the choice of treatment in low-risk PCa patients.« less

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

PubMed Central

Fu, Hangcheng; Liu, Yidong; Xu, Le; Chang, Yuan; Zhou, Lin; Zhang, Weijuan; Yang, Yuanfeng; Xu, Jiejie

2016-01-01

Abstract Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC. The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram. In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy. MUC4 expression is an independent prognostic factor for OS in patients with ccRCC. PMID:27124015

Processing environmental stimuli in paranoid schizophrenia: recognizing facial emotions and performing executive functions.

PubMed

Yu, Shao Hua; Zhu, Jun Peng; Xu, You; Zheng, Lei Lei; Chai, Hao; He, Wei; Liu, Wei Bo; Li, Hui Chun; Wang, Wei

2012-12-01

To study the contribution of executive function to abnormal recognition of facial expressions of emotion in schizophrenia patients. Abnormal recognition of facial expressions of emotion was assayed according to Japanese and Caucasian facial expressions of emotion (JACFEE), Wisconsin card sorting test (WCST), positive and negative symptom scale, and Hamilton anxiety and depression scale, respectively, in 88 paranoid schizophrenia patients and 75 healthy volunteers. Patients scored higher on the Positive and Negative Symptom Scale and the Hamilton Anxiety and Depression Scales, displayed lower JACFEE recognition accuracies and poorer WCST performances. The JACFEE recognition accuracy of contempt and disgust was negatively correlated with the negative symptom scale score while the recognition accuracy of fear was positively with the positive symptom scale score and the recognition accuracy of surprise was negatively with the general psychopathology score in patients. Moreover, the WCST could predict the JACFEE recognition accuracy of contempt, disgust, and sadness in patients, and the perseverative errors negatively predicted the recognition accuracy of sadness in healthy volunteers. The JACFEE recognition accuracy of sadness could predict the WCST categories in paranoid schizophrenia patients. Recognition accuracy of social-/moral emotions, such as contempt, disgust and sadness is related to the executive function in paranoid schizophrenia patients, especially when regarding sadness. Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

PubMed Central

2010-01-01

Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors. PMID:20591134

Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies.

PubMed

Daniels, Susan E; Beineke, Philip; Rhees, Brian; McPherson, John A; Kraus, William E; Thomas, Gregory S; Rosenberg, Steven

2014-10-01

A gene expression score (GES) for obstructive coronary artery disease (CAD) has been validated in two multicenter studies. Receiver-operating characteristics (ROC) analysis of the GES on an expanded Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD defined by quantitative coronary angiography (QCA) or clinical reads yielded similar performance (area under the curve (AUC)=0.70, N=1,502) to the original validation cohort (AUC=0.70, N=526). Analysis of 138 non-Caucasian and 1,364 Caucasian patients showed very similar performance (AUCs=0.72 vs. 0.70). To assess analytic stability, stored samples of the original validation cohort (N=526) was re-tested after 5 years, and the mean score changed from 20.3 to 19.8 after 5 years (N=501, 95 %). To assess patient scores over time, GES was determined on samples from 173 Coronary Obstruction Detection by Molecular Personalized Gene Expression (COMPASS) study (NCT no. 01117506) patients at approximately 1 year post-enrollment. Mean scores increased slightly from 15.9 to 17.3, corresponding to a 2.5 % increase in obstructive CAD likelihood. Changes in cardiovascular medications did not show a significant change in GES.

Progastrin: a potential predictive marker of liver metastasis in colorectal cancer.

PubMed

Westwood, David A; Patel, Oneel; Christophi, Christopher; Shulkes, Arthur; Baldwin, Graham S

2017-07-01

Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer. Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included. The patients either had stage IIa disease with greater than 3-year disease-free survival without adjuvant therapy or stage IV disease with liver metastases on staging CT. Progastrin expression in tumour sections was scored with reference to the intensity and area of immunohistochemical staining. Progastrin expression by stage IV tumours was significantly greater than stage IIa tumours with mean progastrin immunopositivity scores of 2.1 ± 0.2 versus 0.5 ± 0.2, respectively (P < 0.001). This is the first study to show that progastrin expression may be predictive of aggressive tumour behaviour in patients with colorectal cancer and supports its clinical relevance and potential use as a biomarker.

Possible pathways used to predict different stages of lung adenocarcinoma.

PubMed

Chen, Xiaodong; Duan, Qiongyu; Xuan, Ying; Sun, Yunan; Wu, Rong

2017-04-01

We aimed to find some specific pathways that can be used to predict the stage of lung adenocarcinoma.RNA-Seq expression profile data and clinical data of lung adenocarcinoma (stage I [37], stage II 161], stage III [75], and stage IV [45]) were obtained from the TCGA dataset. The differentially expressed genes were merged, correlation coefficient matrix between genes was constructed with correlation analysis, and unsupervised clustering was carried out with hierarchical clustering method. The specific coexpression network in every stage was constructed with cytoscape software. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed with KOBAS database and Fisher exact test. Euclidean distance algorithm was used to calculate total deviation score. The diagnostic model was constructed with SVM algorithm.Eighteen specific genes were obtained by getting intersection of 4 group differentially expressed genes. Ten significantly enriched pathways were obtained. In the distribution map of 10 pathways score in different groups, degrees that sample groups deviated from the normal level were as follows: stage I < stage II < stage III < stage IV. The pathway score of 4 stages exhibited linear change in some pathways, and the score of 1 or 2 stages were significantly different from the rest stages in some pathways. There was significant difference between dead and alive for these pathways except thyroid hormone signaling pathway.Those 10 pathways are associated with the development of lung adenocarcinoma and may be able to predict different stages of it. Furthermore, these pathways except thyroid hormone signaling pathway may be able to predict the prognosis.

The stroke impairment assessment set: its internal consistency and predictive validity.

PubMed

Tsuji, T; Liu, M; Sonoda, S; Domen, K; Chino, N

2000-07-01

To study the scale quality and predictive validity of the Stroke Impairment Assessment Set (SIAS) developed for stroke outcome research. Rasch analysis of the SIAS; stepwise multiple regression analysis to predict discharge functional independence measure (FIM) raw scores from demographic data, the SIAS scores, and the admission FIM scores; cross-validation of the prediction rule. Tertiary rehabilitation center in Japan. One hundred ninety stroke inpatients for the study of the scale quality and the predictive validity; a second sample of 116 stroke inpatients for the cross-validation study. Mean square fit statistics to study the degree of fit to the unidimensional model; logits to express item difficulties; discharge FIM scores for the study of predictive validity. The degree of misfit was acceptable except for the shoulder range of motion (ROM), pain, visuospatial function, and speech items; and the SIAS items could be arranged on a common unidimensional scale. The difficulty patterns were identical at admission and at discharge except for the deep tendon reflexes, ROM, and pain items. They were also similar for the right- and left-sided brain lesion groups except for the speech and visuospatial items. For the prediction of the discharge FIM scores, the independent variables selected were age, the SIAS total scores, and the admission FIM scores; and the adjusted R2 was .64 (p < .0001). Stability of the predictive equation was confirmed in the cross-validation sample (R2 = .68, p < .001). The unidimensionality of the SIAS was confirmed, and the SIAS total scores proved useful for stroke outcome prediction.

Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer

PubMed Central

Peláez-García, Alberto; Yébenes, Laura; Berjón, Alberto; Angulo, Antonia; Zamora, Pilar; Sánchez-Méndez, José Ignacio; Espinosa, Enrique; Redondo, Andrés; Heredia-Soto, Victoria; Mendiola, Marta; Feliú, Jaime

2017-01-01

Purpose To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. Methods Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). Results The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). Conclusions This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test. PMID:28886093

High truncated-O-glycan score predicts adverse clinical outcome in patients with localized clear-cell renal cell carcinoma after surgery.

PubMed

NguyenHoang, SonTung; Liu, Yidong; Xu, Le; Zhou, Lin; Chang, Yuan; Fu, Qiang; Liu, Zheng; Lin, Zongming; Xu, Jiejie

2017-10-03

Truncated O-glycans, including Tn-antigen, sTn-antigen, T-antigen, sT-antigen, are incomplete glycosylated structures and their expression occur frequently in tumor tissue. The study aims to evaluate the abundance of each truncated O-glycans and its clinical significance in postoperative patients with localized clear-cell renal cell carcinoma (ccRCC). We used immunohistochemical testing to analyze the expression of truncated O-glycans in tumor specimens from 401 patients with localized ccRCC. Truncated-O-glycan score was built by integrating the expression level of Tn-, sTn- and sT-antigen. Kaplan-Meier survival and Cox regression analysis were done to compare clinical outcomes in subgroups. Receiver operating characteristic (ROC) was applied to assess the impact of prognostic factors on overall survival (OS) and recurrence-free survival (RFS). The results identified Tn-, sTn-, sT-antigen as independent prognosticators. The OS and RFS were shortened among the 198 (49.4%) patients with high Truncated-O-glycan score than among the 203 (50.6%) patients with low score (hazard ratio for OS, 7.060; 95% confidence interval [CI]: 2.765 to 18.027; p <0.001; for RFS, 4.612; 95% CI: 2.141 to 9.931; p <0.001). There is no difference between low-risk patients and high-risk patients in low score group ( p = 0.987). High-risk patients with low score showed a better prognosis than low-risk patient with high score ( p = 0.029). The Truncated-O-glycan score showed better prognostic value for OS (AUC: 0.739, p = 0.003) and RFS (AUC: 0.719, p = 0.003) than TNM stage. In summary, the high Truncated-O-glycan score could predict adverse clinical outcome in localized ccRCC patients after surgery.

[Detection and analysis of the characteristic expression of microRNAs of anal fistula patients].

PubMed

Qiu, Jianming; Yu, Jiping; Yang, Guangen; Xu, Kan; Tao, Yong; Lin, Ali; Wang, Dong

2016-07-01

To detect and analyze the characteristic miRNAs profile of anal fistula and explore their possible target genes and potential clinical significance. The anal mucosa close to the hemorrhoids were collected from three patients undergoing fistulectomy and hemorrhoidectomy (fistula group) as well as three patients receiving only hemorroidectomy(hemorrhoids group), matching with fistula group in age, gender and body weight. miRNA microarray was used to compare the expression of 1 285 human miRNAs of the anal mucosa between two groups. Cluster analysis was adopted to analyze the accumulation of the differentially expressed miRNAs(P<0.05, fold≥2.0 or ≤0.5) and their target genes were predicted with 10 softwares such as DIANAmT, miRanda, miRDB, miRWalk etc. Comprehensive scoring was performed to identify genes with highest predictive score. Gene ontology (GO) concentration technique was used to analyze the target gene-associated biological process. Immunohistochemistry was used to examine protein expression of genes with the highest score. Among 1285 miRNAs in fistula group, 13 miRNAs were differentially expressed with those in hemorrhoid group, including 2 of up-regulation and 11 of down-regulation. Paired t test showed that in fistula group, miRNA-3609 up-regulation was 5.98 folds(P=0.0231) and miR-181a-2-3p down-regulation was 0.13 folds(P=0.0067) compared to those in hemorrhoid group, which had the greatest differential expression. Cluster analysis suggested that up-regulated miR-3609 and miR-6086 had similar change trend in both groups. Among 11 down-regulated miRNAs, miR-125bp-1-3p and miR-548q had similar expression and other 9 miRNAs had similar expression as well, including miR-1185-1-3p, miR-532-3p, miR-1233-5p, miR-769-5p, miR-149-5p, miR-99b-3p, miR-141-3p, miR-138-5p, and miR-181a-2-3p. Target gene prediction analysis of above 13 genes showed that 7 miRNAs(53.8%) were eligible to predict their potential target genes, yielding totally 104 possible target genes. The rest of 6 miRNAs(46.2%) failed to predict any target gene. The highest score in prediction of target gene was chitinase 1(ChIT1) and its corresponding differential miRNA was miR-769-5p(r=-0.94286, P=0.0167). Gene ontology analysis showed that the most associated biological process related with these 104 target genes was keratinization, immune response and signal transduction. Immunohistochemistry revealed ChiT1 expression of anal mucosa in fistula group was significantly higher compared to hemorrhoid group(P<0.01). There is a characteristic miRNAs profile in anal fistula patients, which may play a role in the occurrence and development of anal fistula.

Parenting stress and anger expression as predictors of child abuse potential.

PubMed

Rodriguez, C M; Green, A J

1997-04-01

To explore one potential pathway to physical child abuse, the present investigation used hierarchical regression analysis using measures of parenting stress and anger expression to jointly predict child abuse potential. The Parenting Stress Index, State-Trait Anger Expression Inventory, and the Child Abuse Potential Inventory were administered to two different samples of New Zealand parents. As expected, both studies revealed parenting stress and anger expression and were individually positively correlated with child abuse potential: the major finding involved the strong point contribution of parenting stress and anger expression in predicting Child Abuse Potential Inventory scores. Application of findings for intervention and prevention are discussed.

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

PubMed Central

2010-01-01

Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID:20584321

Analyzing gene expression from relative codon usage bias in Yeast genome: a statistical significance and biological relevance.

PubMed

Das, Shibsankar; Roymondal, Uttam; Sahoo, Satyabrata

2009-08-15

Based on the hypothesis that highly expressed genes are often characterized by strong compositional bias in terms of codon usage, there are a number of measures currently in use that quantify codon usage bias in genes, and hence provide numerical indices to predict the expression levels of genes. With the recent advent of expression measure from the score of the relative codon usage bias (RCBS), we have explicitly tested the performance of this numerical measure to predict the gene expression level and illustrate this with an analysis of Yeast genomes. In contradiction with previous other studies, we observe a weak correlations between GC content and RCBS, but a selective pressure on the codon preferences in highly expressed genes. The assertion that the expression of a given gene depends on the score of relative codon usage bias (RCBS) is supported by the data. We further observe a strong correlation between RCBS and protein length indicating natural selection in favour of shorter genes to be expressed at higher level. We also attempt a statistical analysis to assess the strength of relative codon bias in genes as a guide to their likely expression level, suggesting a decrease of the informational entropy in the highly expressed genes.

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53.

PubMed

Walter, R F H; Mairinger, F D; Ting, S; Vollbrecht, C; Mairinger, T; Theegarten, D; Christoph, D C; Schmid, K W; Wohlschlaeger, J

2015-03-03

Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.

A long-term predictive validity study: can the CDI Short Form be used to predict language and early literacy skills four years later?

PubMed

Can, Dilara Deniz; Ginsburg-Block, Marika; Golinkoff, Roberta Michnick; Hirsh-Pasek, Kathryn

2013-09-01

This longitudinal study examined the predictive validity of the MacArthur Communicative Developmental Inventories-Short Form (CDI-SF), a parent report questionnaire about children's language development (Fenson, Pethick, Renda, Cox, Dale & Reznick, 2000). Data were first gathered from parents on the CDI-SF vocabulary scores for seventy-six children (mean age=1 ; 10). Four years later (mean age=6 ; 1), children were assessed on language outcomes (expressive vocabulary, syntax, semantics and pragmatics) and code-related skills, including phonemic awareness, word recognition and decoding skills. Hierarchical regression analyses revealed that early expressive vocabulary accounted for 17% of the variance in picture vocabulary, 11% of the variance in syntax, and 7% of the variance in semantics, while not accounting for any variance in pragmatics in kindergarten. CDI-SF scores did not predict code-related skills in kindergarten. The importance of early vocabulary skills for later language development and CDI-SF as a valuable research tool are discussed.

Predictive Efficiency of Direct, Repeated Measurement: An Analysis of Cost and Accuracy in Classification.

ERIC Educational Resources Information Center

Marston, Doug; And Others

Two studies were conducted to examine the efficacy of direct measurement, standardized achievement tests, and aptitude-achievement discrepancy scores in distinguishing learning disabled (LD) and nonlearning disabled (NLD) students in grades 3 to 6. For both reading (Study I) and written expression (Study II), students' scores on direct and…

Comparative study of joint analysis of microarray gene expression data in survival prediction and risk assessment of breast cancer patients

PubMed Central

2016-01-01

Abstract Microarray gene expression data sets are jointly analyzed to increase statistical power. They could either be merged together or analyzed by meta-analysis. For a given ensemble of data sets, it cannot be foreseen which of these paradigms, merging or meta-analysis, works better. In this article, three joint analysis methods, Z -score normalization, ComBat and the inverse normal method (meta-analysis) were selected for survival prognosis and risk assessment of breast cancer patients. The methods were applied to eight microarray gene expression data sets, totaling 1324 patients with two clinical endpoints, overall survival and relapse-free survival. The performance derived from the joint analysis methods was evaluated using Cox regression for survival analysis and independent validation used as bias estimation. Overall, Z -score normalization had a better performance than ComBat and meta-analysis. Higher Area Under the Receiver Operating Characteristic curve and hazard ratio were also obtained when independent validation was used as bias estimation. With a lower time and memory complexity, Z -score normalization is a simple method for joint analysis of microarray gene expression data sets. The derived findings suggest further assessment of this method in future survival prediction and cancer classification applications. PMID:26504096

Predicting Ki67% expression from DCE-MR images of breast tumors using textural kinetic features in tumor habitats

NASA Astrophysics Data System (ADS)

Chaudhury, Baishali; Zhou, Mu; Farhidzadeh, Hamidreza; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Weinfurtner, Robert J.; Drukteinis, Jennifer S.

2016-03-01

The use of Ki67% expression, a cell proliferation marker, as a predictive and prognostic factor has been widely studied in the literature. Yet its usefulness is limited due to inconsistent cut off scores for Ki67% expression, subjective differences in its assessment in various studies, and spatial variation in expression, which makes it difficult to reproduce as a reliable independent prognostic factor. Previous studies have shown that there are significant spatial variations in Ki67% expression, which may limit its clinical prognostic utility after core biopsy. These variations are most evident when examining the periphery of the tumor vs. the core. To date, prediction of Ki67% expression from quantitative image analysis of DCE-MRI is very limited. This work presents a novel computer aided diagnosis framework to use textural kinetics to (i) predict the ratio of periphery Ki67% expression to core Ki67% expression, and (ii) predict Ki67% expression from individual tumor habitats. The pilot cohort consists of T1 weighted fat saturated DCE-MR images from 17 patients. Support vector regression with a radial basis function was used for predicting the Ki67% expression and ratios. The initial results show that texture features from individual tumor habitats are more predictive of the Ki67% expression ratio and spatial Ki67% expression than features from the whole tumor. The Ki67% expression ratio could be predicted with a root mean square error (RMSE) of 1.67%. Quantitative image analysis of DCE-MRI using textural kinetic habitats, has the potential to be used as a non-invasive method for predicting Ki67 percentage and ratio, thus more accurately reporting high KI-67 expression for patient prognosis.

Benefits of Expressive Writing in Lowering Rumination and Depressive Symptoms

ERIC Educational Resources Information Center

Gortner, Eva-Marie; Rude, Stephanie S.; Pennebaker, James W.

2006-01-01

Depression-vulnerable college students (with both elevated prior depressive symptoms and low current depressive symptoms) wrote on 3 consecutive days in either an expressive writing or a control condition. As predicted, participants scoring above the median on the suppression scale of the Emotion Regulation Questionnaire (Gross & John, 2003)…

Integration of somatic mutation, expression and functional data reveals potential driver genes predictive of breast cancer survival.

PubMed

Suo, Chen; Hrydziuszko, Olga; Lee, Donghwan; Pramana, Setia; Saputra, Dhany; Joshi, Himanshu; Calza, Stefano; Pawitan, Yudi

2015-08-15

Genome and transcriptome analyses can be used to explore cancers comprehensively, and it is increasingly common to have multiple omics data measured from each individual. Furthermore, there are rich functional data such as predicted impact of mutations on protein coding and gene/protein networks. However, integration of the complex information across the different omics and functional data is still challenging. Clinical validation, particularly based on patient outcomes such as survival, is important for assessing the relevance of the integrated information and for comparing different procedures. An analysis pipeline is built for integrating genomic and transcriptomic alterations from whole-exome and RNA sequence data and functional data from protein function prediction and gene interaction networks. The method accumulates evidence for the functional implications of mutated potential driver genes found within and across patients. A driver-gene score (DGscore) is developed to capture the cumulative effect of such genes. To contribute to the score, a gene has to be frequently mutated, with high or moderate mutational impact at protein level, exhibiting an extreme expression and functionally linked to many differentially expressed neighbors in the functional gene network. The pipeline is applied to 60 matched tumor and normal samples of the same patient from The Cancer Genome Atlas breast-cancer project. In clinical validation, patients with high DGscores have worse survival than those with low scores (P = 0.001). Furthermore, the DGscore outperforms the established expression-based signatures MammaPrint and PAM50 in predicting patient survival. In conclusion, integration of mutation, expression and functional data allows identification of clinically relevant potential driver genes in cancer. The documented pipeline including annotated sample scripts can be found in http://fafner.meb.ki.se/biostatwiki/driver-genes/. yudi.pawitan@ki.se Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freedland, Stephen J., E-mail: steve.freedland@duke.edu; Department of Surgery; Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-upmore » for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less

Accurate Identification of Fear Facial Expressions Predicts Prosocial Behavior

PubMed Central

Marsh, Abigail A.; Kozak, Megan N.; Ambady, Nalini

2009-01-01

The fear facial expression is a distress cue that is associated with the provision of help and prosocial behavior. Prior psychiatric studies have found deficits in the recognition of this expression by individuals with antisocial tendencies. However, no prior study has shown accuracy for recognition of fear to predict actual prosocial or antisocial behavior in an experimental setting. In 3 studies, the authors tested the prediction that individuals who recognize fear more accurately will behave more prosocially. In Study 1, participants who identified fear more accurately also donated more money and time to a victim in a classic altruism paradigm. In Studies 2 and 3, participants’ ability to identify the fear expression predicted prosocial behavior in a novel task designed to control for confounding variables. In Study 3, accuracy for recognizing fear proved a better predictor of prosocial behavior than gender, mood, or scores on an empathy scale. PMID:17516803

Accurate identification of fear facial expressions predicts prosocial behavior.

PubMed

Marsh, Abigail A; Kozak, Megan N; Ambady, Nalini

2007-05-01

The fear facial expression is a distress cue that is associated with the provision of help and prosocial behavior. Prior psychiatric studies have found deficits in the recognition of this expression by individuals with antisocial tendencies. However, no prior study has shown accuracy for recognition of fear to predict actual prosocial or antisocial behavior in an experimental setting. In 3 studies, the authors tested the prediction that individuals who recognize fear more accurately will behave more prosocially. In Study 1, participants who identified fear more accurately also donated more money and time to a victim in a classic altruism paradigm. In Studies 2 and 3, participants' ability to identify the fear expression predicted prosocial behavior in a novel task designed to control for confounding variables. In Study 3, accuracy for recognizing fear proved a better predictor of prosocial behavior than gender, mood, or scores on an empathy scale.

A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

PubMed

Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

2014-09-01

Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Bacillus anthracis genome organization in light of whole transcriptome sequencing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Jeffrey; Zhu, Wenhan; Passalacqua, Karla D.

2010-03-22

Emerging knowledge of whole prokaryotic transcriptomes could validate a number of theoretical concepts introduced in the early days of genomics. What are the rules connecting gene expression levels with sequence determinants such as quantitative scores of promoters and terminators? Are translation efficiency measures, e.g. codon adaptation index and RBS score related to gene expression? We used the whole transcriptome shotgun sequencing of a bacterial pathogen Bacillus anthracis to assess correlation of gene expression level with promoter, terminator and RBS scores, codon adaptation index, as well as with a new measure of gene translational efficiency, average translation speed. We compared computationalmore » predictions of operon topologies with the transcript borders inferred from RNA-Seq reads. Transcriptome mapping may also improve existing gene annotation. Upon assessment of accuracy of current annotation of protein-coding genes in the B. anthracis genome we have shown that the transcriptome data indicate existence of more than a hundred genes missing in the annotation though predicted by an ab initio gene finder. Interestingly, we observed that many pseudogenes possess not only a sequence with detectable coding potential but also promoters that maintain transcriptional activity.« less

ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study.

PubMed

Romano, Francesco Jacopo; Guadagno, Elia; Solari, Domenico; Borrelli, Giorgio; Pignatiello, Sara; Cappabianca, Paolo; Del Basso De Caro, Marialaura

2018-06-01

Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs. © 2018 Wiley Periodicals, Inc.

A comparison of the Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Score (GCS) in predictive modelling in traumatic brain injury.

PubMed

Kasprowicz, Magdalena; Burzynska, Malgorzata; Melcer, Tomasz; Kübler, Andrzej

2016-01-01

To compare the performance of multivariate predictive models incorporating either the Full Outline of UnResponsiveness (FOUR) score or Glasgow Coma Score (GCS) in order to test whether substituting GCS with the FOUR score in predictive models for outcome in patients after TBI is beneficial. A total of 162 TBI patients were prospectively enrolled in the study. Stepwise logistic regression analysis was conducted to compare the prediction of (1) in-ICU mortality and (2) unfavourable outcome at 3 months post-injury using as predictors either the FOUR score or GCS along with other factors that may affect patient outcome. The areas under the ROC curves (AUCs) were used to compare the discriminant ability and predictive power of the models. The internal validation was performed with bootstrap technique and expressed as accuracy rate (AcR). The FOUR score, age, the CT Rotterdam score, systolic ABP and being placed on ventilator within day one (model 1: AUC: 0.906 ± 0.024; AcR: 80.3 ± 4.8%) performed equally well in predicting in-ICU mortality as the combination of GCS with the same set of predictors plus pupil reactivity (model 2: AUC: 0.913 ± 0.022; AcR: 81.1 ± 4.8%). The CT Rotterdam score, age and either the FOUR score (model 3) or GCS (model 4) equally well predicted unfavourable outcome at 3 months post-injury (AUC: 0.852 ± 0.037 vs. 0.866 ± 0.034; AcR: 72.3 ± 6.6% vs. 71.9%±6.6%, respectively). Adding the FOUR score or GCS at discharge from ICU to predictive models for unfavourable outcome increased significantly their performances (AUC: 0.895 ± 0.029, p = 0.05; AcR: 76.1 ± 6.5%; p < 0.004 when compared with model 3; and AUC: 0.918 ± 0.025, p < 0.05; AcR: 79.6 ± 7.2%, p < 0.009 when compared with model 4), but there was no benefit from substituting GCS with the FOUR score. Results showed that FOUR score and GCS perform equally well in multivariate predictive modelling in TBI.

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

PubMed Central

Schmidt, Florian; Gasparoni, Nina; Gasparoni, Gilles; Gianmoena, Kathrin; Cadenas, Cristina; Polansky, Julia K.; Ebert, Peter; Nordström, Karl; Barann, Matthias; Sinha, Anupam; Fröhler, Sebastian; Xiong, Jieyi; Dehghani Amirabad, Azim; Behjati Ardakani, Fatemeh; Hutter, Barbara; Zipprich, Gideon; Felder, Bärbel; Eils, Jürgen; Brors, Benedikt; Chen, Wei; Hengstler, Jan G.; Hamann, Alf; Lengauer, Thomas; Rosenstiel, Philip; Walter, Jörn; Schulz, Marcel H.

2017-01-01

The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid costly TF ChIP-seq assays. Thus, it is important to develop computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices. TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq. Additionally, Histone-Marks (HMs) can be used to identify candidate TF binding sites. TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength. Using machine learning, we find low affinity binding sites to improve our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites. Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance. In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq data sets. Finally, these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively. PMID:27899623

Anger and the ABC model underlying Rational-Emotive Behavior Therapy.

PubMed

Ziegler, Daniel J; Smith, Phillip N

2004-06-01

The ABC model underlying Ellis's Rational-Emotive Behavior Therapy predicts that people who think more irrationally should display greater trait anger than do people who think less irrationally. This study tested this prediction regarding the ABC model. 186 college students were administered the Survey of Personal Beliefs and the State-Trait Anger Expression Inventory-Second Edition to measure irrational thinking and trait anger, respectively. Students who scored higher on Overall Irrational Thinking and Low Frustration Tolerance scored significantly higher on Trait Anger than did those who scored lower on Overall Irrational Thinking and Low Frustration Tolerance. This indicates support for the ABC model, especially Ellis's construct of irrational beliefs which is central to the model.

The receptive-expressive gap in the vocabulary of young second-language learners: Robustness and possible mechanisms.

PubMed

Gibson, Todd A; Oller, D Kimbrough; Jarmulowicz, Linda; Ethington, Corinna A

2012-01-01

Adults and children learning a second language show difficulty accessing expressive vocabulary that appears accessible receptively in their first language (L1). We call this discrepancy the receptive-expressive gap. Kindergarten Spanish (L1) - English (L2) sequential bilinguals were given standardized tests of receptive and expressive vocabulary in both Spanish and English. We found a small receptive-expressive gap in English but a large receptive-expressive gap in Spanish. We categorized children as having had high or low levels of English exposure based on demographic variables and found that the receptive-expressive gap persisted across both levels of English exposure. Regression analyses revealed that variables predicting both receptive and expressive vocabulary scores failed to predict the receptive-expressive gap. The results suggest that the onset of the receptive-expressive gap in L1 must have been abrupt. We discuss possible mechanisms underlying the phenomenon.

The receptive-expressive gap in the vocabulary of young second-language learners: Robustness and possible mechanisms

PubMed Central

Gibson, Todd A.; Oller, D. Kimbrough; Jarmulowicz, Linda; Ethington, Corinna A.

2010-01-01

Adults and children learning a second language show difficulty accessing expressive vocabulary that appears accessible receptively in their first language (L1). We call this discrepancy the receptive-expressive gap. Kindergarten Spanish (L1) - English (L2) sequential bilinguals were given standardized tests of receptive and expressive vocabulary in both Spanish and English. We found a small receptive-expressive gap in English but a large receptive-expressive gap in Spanish. We categorized children as having had high or low levels of English exposure based on demographic variables and found that the receptive-expressive gap persisted across both levels of English exposure. Regression analyses revealed that variables predicting both receptive and expressive vocabulary scores failed to predict the receptive-expressive gap. The results suggest that the onset of the receptive-expressive gap in L1 must have been abrupt. We discuss possible mechanisms underlying the phenomenon. PMID:22247648

Length of stay of stroke rehabilitation inpatients: prediction through the functional independence measure.

PubMed

Franchignoni, F; Tesio, L; Martino, M T; Benevolo, E; Castagna, M

1998-01-01

A model for prediction of length of stay (LOS, in days) of stroke rehabilitation inpatients was developed, based on patients' age (years) and function at admission (scored on the Functional Independence Measure, FIMSM). One hundred and twenty-nine cases, consecutively admitted to three free-standing rehabilitation centres in Italy, were analyzed. A multiple linear regression using forward stepwise selection procedure was adopted. Median admission and discharge scores were: 57 and 75 for the total FIM score, 29 and 48 for the 13-item motor FIM subscore, 29 and 30 for the 5-item cognitive FIM subscore (potential range: 18-126, 13-91, 5-35, respectively). Median LOS was 44 days (interquartile range 30-62). The logLOS predictive model included three FIM items ("toilet transfer", TTr; "social interaction"; "expression") and patient's age (R2 = 0.48). TTr alone explained 31.3% of the variance of logLOS. These results are consistent with previous American studies, showing that FIM scores at admission are strong predictors of patients' LOS, with the transfer items having the greatest predictive power.

Cognitive, Environmental, and Linguistic Predictors of Syntax in Fragile X Syndrome and Down Syndrome

ERIC Educational Resources Information Center

Estigarribia, Bruno; Martin, Gary E.; Roberts, Joanne E.

2012-01-01

Purpose: To examine which cognitive, environmental, and speech-language variables predict expressive syntax in boys with fragile X syndrome (FXS), boys with Down syndrome (DS), and typically developing (TD) boys, and whether predictive relationships differed by group. Method: We obtained Index of Productive Syntax ( Scarborough, 1990) scores for…

Making Online Learning Personal: Evolution, Evidentiary Reasoning, and Self-Regulation in an Online Curriculum

NASA Astrophysics Data System (ADS)

Marsteller, Robert B.

An online curriculum about biological evolution was designed according to the Promoting Evidentiary Reasoning and Self-regulation Online (PERSON) theoretical framework. PERSON is an attempt to develop online science instruction focused on supporting evidentiary reasoning and self-regulation. An efficacy study was conducted with 80 suburban high school biology students using a design-based research approach to develop a curriculum to promote biological evolution understandings, evidentiary reasoning, and self-regulation. Data sources and instruments included (1) the Biological Evolution Assessment Measurement (BEAM); (2) the modified Motivated Strategies for Learning Questionnaire (MSLQ); (3) discussion forum posts; (4) formative assessments of evidence based reasoning; (5) Prediction, Monitoring, and Reflection forms (PMR); (6) the Online Instruction Questionnaire; and (7) field notes. Findings revealed that BEAM posttest scores were significantly greater than pretest scores for items designed to measure biological evolution content knowledge and evidentiary reasoning. Students tracked in a lower level biology course showed improvement in biological evolution understandings and evidentiary reasoning. It was found that performance on daily evidentiary reasoning tasks strongly predicted BEAM posttest scores. However, findings revealed that students did not meet local standards for performance on items designed to measure evidentiary reasoning. Students expressed a variety of opinions about their learning experiences with the online curriculum. Some students expressed a definite preference for traditional learning environments, while others expressed a definite preference for online learning. Self-regulatory ability did not significantly predict BEAM gain scores. Further, self-regulatory ability was not demonstrably improved as a result of this intervention. Implications for designing science instruction in asynchronous online learning environments to support evidentiary reasoning and self-regulation are discussed.

Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders.

PubMed

Coleman, Jonathan R I; Lester, Kathryn J; Roberts, Susanna; Keers, Robert; Lee, Sang Hyuck; De Jong, Simone; Gaspar, Héléna; Teismann, Tobias; Wannemüller, André; Schneider, Silvia; Jöhren, Peter; Margraf, Jürgen; Breen, Gerome; Eley, Thalia C

2017-04-01

Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

PubMed

Giridhar, Karthik V; Sosa, Carlos P; Hillman, David W; Sanhueza, Cristobal; Dalpiaz, Candace L; Costello, Brian A; Quevedo, Fernando J; Pitot, Henry C; Dronca, Roxana S; Ertz, Donna; Cheville, John C; Donkena, Krishna Vanaja; Kohli, Manish

2017-11-03

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04-0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05-0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only ( p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma

PubMed Central

Sosa, Carlos P.; Hillman, David W.; Sanhueza, Cristobal; Dalpiaz, Candace L.; Costello, Brian A.; Quevedo, Fernando J.; Pitot, Henry C.; Dronca, Roxana S.; Ertz, Donna; Cheville, John C.; Donkena, Krishna Vanaja; Kohli, Manish

2017-01-01

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04–0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05–0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies. PMID:29099775

Classification of Airflow Limitation Based on z-Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Tejero, Elena; Prats, Eva; Casitas, Raquel; Galera, Raúl; Pardo, Paloma; Gavilán, Adelaida; Martínez-Cerón, Elisabet; Cubillos-Zapata, Carolina; Del Peso, Luis; García-Río, Francisco

2017-08-01

Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted of FEV 1 in patients with chronic obstructive pulmonary disease (COPD). A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow-up, totaling 10,322 person-years. All-cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z-score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z-score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5-year survival was slightly higher for FEV 1 expressed as percentage of predicted than as z-score (area under the curve: 0.714-0.760 vs. 0.649-0.708, respectively). A severity-dependent relationship between AL grades by z-score and mortality was only detected in patients younger than age 60 years. In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.

Combining Evidence of Preferential Gene-Tissue Relationships from Multiple Sources

PubMed Central

Guo, Jing; Hammar, Mårten; Öberg, Lisa; Padmanabhuni, Shanmukha S.; Bjäreland, Marcus; Dalevi, Daniel

2013-01-01

An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity. PMID:23950964

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction.

PubMed

Schmidt, Florian; Gasparoni, Nina; Gasparoni, Gilles; Gianmoena, Kathrin; Cadenas, Cristina; Polansky, Julia K; Ebert, Peter; Nordström, Karl; Barann, Matthias; Sinha, Anupam; Fröhler, Sebastian; Xiong, Jieyi; Dehghani Amirabad, Azim; Behjati Ardakani, Fatemeh; Hutter, Barbara; Zipprich, Gideon; Felder, Bärbel; Eils, Jürgen; Brors, Benedikt; Chen, Wei; Hengstler, Jan G; Hamann, Alf; Lengauer, Thomas; Rosenstiel, Philip; Walter, Jörn; Schulz, Marcel H

2017-01-09

The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid costly TF ChIP-seq assays. Thus, it is important to develop computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices. TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq. Additionally, Histone-Marks (HMs) can be used to identify candidate TF binding sites. TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength. Using machine learning, we find low affinity binding sites to improve our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites. Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance. In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq data sets. Finally, these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Ion Channel Gene Expression in Lung Adenocarcinoma: Potential Role in Prognosis and Diagnosis

PubMed Central

Ko, Jae-Hong; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Eun A.; Zhou, Tong

2014-01-01

Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts. PMID:24466154

Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.

PubMed

Gianni, Luca; Zambetti, Milvia; Clark, Kim; Baker, Joffre; Cronin, Maureen; Wu, Jenny; Mariani, Gabriella; Rodriguez, Jaime; Carcangiu, Marialuisa; Watson, Drew; Valagussa, Pinuccia; Rouzier, Roman; Symmans, W Fraser; Ross, Jeffrey S; Hortobagyi, Gabriel N; Pusztai, Lajos; Shak, Steven

2005-10-10

We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher malignancy of prostate lesions. Using multivariate analysis, we also found that SERPING1 expression was independent prognostic marker of poor disease-free survival and biochemical recurrence-free survival. SERPING1 may play an important role in PCa and can be serve as a novel marker in diagnosis and prognostic prediction in PCa. In addition, levels of SERPING1 can help identify low-risk prostate to provide reference for patients with PCa to accept active surveillance and reduce overtreatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Predicting reading ability in teenagers who are deaf or hard of hearing: A longitudinal analysis of language and reading.

PubMed

Worsfold, Sarah; Mahon, Merle; Pimperton, Hannah; Stevenson, Jim; Kennedy, Colin

2018-06-01

Deaf and hard of hearing (D/HH) children and young people are known to show group-level deficits in spoken language and reading abilities relative to their hearing peers. However, there is little evidence on the longitudinal predictive relationships between language and reading in this population. To determine the extent to which differences in spoken language ability in childhood predict reading ability in D/HH adolescents. and procedures: Participants were drawn from a population-based cohort study and comprised 53 D/HH teenagers, who used spoken language, and a comparison group of 38 normally hearing teenagers. All had completed standardised measures of spoken language (expression and comprehension) and reading (accuracy and comprehension) at 6-10 and 13-19 years of age. and results: Forced entry stepwise regression showed that, after taking reading ability at age 8 years into account, language scores at age 8 years did not add significantly to the prediction of Reading Accuracy z-scores at age 17 years (change in R 2  = 0.01, p = .459) but did make a significant contribution to the prediction of Reading Comprehension z-scores at age 17 years (change in R 2  = 0.17, p < .001). and implications: In D/HH individuals who are spoken language users, expressive and receptive language skills in middle childhood predict reading comprehension ability in adolescence. Continued intervention to support language development beyond primary school has the potential to benefit reading comprehension and hence educational access for D/HH adolescents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Integrated multigene expression panel to prognosticate patients with gastric cancer.

PubMed

Kanda, Mitsuro; Murotani, Kenta; Tanaka, Haruyoshi; Miwa, Takashi; Umeda, Shinichi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Hattori, Norifumi; Suenaga, Masaya; Yamada, Suguru; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-04-10

Most of the proposed individual markers had limited clinical utility due to the inherent biological and genetic heterogeneity of gastric cancer. We aimed to build a new molecular-based model to predict prognosis in patients with gastric cancer. A total of 200 patients who underwent gastric resection for gastric cancer were divided into learning and validation cohorts using a table of random numbers in a 1:1 ratio. In the learning cohort, mRNA expression levels of 15 molecular markers in gastric tissues were analyzed and concordance index (C-index) values of all single and combinations of the 15 candidate markers for overall survival were calculated. The multigene expression panel was designed according to C-index values and the subpopulation index. Expression scores were determined with weighting according to the coefficient of each constituent. The reproducibility of the panel was evaluated in the validation cohort. C-index values of the 15 single candidate markers ranged from 0.506-0.653. Among 32,767 combinations, the optimal and balanced expression panel comprised four constituents ( MAGED2, SYT8, BTG1 , and FAM46 ) and the C-index value was 0.793. Using this panel, patients were provisionally categorized with scores of 1-3, and clearly stratified into favorable, intermediate, and poor overall survival groups. In the validation cohort, both overall and disease-free survival rates decreased incrementally with increasing expression scores. Multivariate analysis revealed that the expression score was an independent prognostic factor for overall survival after curative gastrectomy. We developed an integrated multigene expression panel that simply and accurately stratified risk of patients with gastric cancer.

MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, M; Craft, D

Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchicalmore » clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve cancer classification using biological pathways. Patients are classified with greater specificity and physiological relevance as compared to current gene-specific approaches. Focus now moves to utilizing PICS for pan-cancer patient-specific treatment response prediction.« less

Prediction of cardioembolic, arterial and lacunar causes of cryptogenic stroke by gene expression and infarct location

PubMed Central

Jickling, Glen C; Stamova, Boryana; Ander, Bradley P; Zhan, Xinhua; Liu, Dazhi; Sison, Shara-Mae; Verro, Piero; Sharp, Frank R

2012-01-01

Background and Purpose The cause of ischemic stroke remains unclear, or cryptogenic, in as many as 35% of stroke patients. Not knowing the cause of stroke restricts optimal implementation of prevention therapy and limits stroke research. We demonstrate how gene expression profiles in blood can be used in conjunction with a measure of infarct location on neuroimaging to predict a probable cause in cryptogenic stroke. Methods The cause of cryptogenic stroke was predicted using previously described profiles of differentially expressed genes characteristic of patients with cardioembolic, arterial and lacunar stroke. RNA was isolated from peripheral blood of 131 cryptogenic strokes and compared to profiles derived from 149 strokes of known cause. Each sample was run on Affymetrix U133 Plus2.0 microarrays. Cause of cryptogenic stroke was predicted using gene expression in blood and infarct location. Results Cryptogenic strokes were predicted to be 58% cardioembolic, 18% arterial, 12% lacunar and 12% unclear etiology. Cryptogenic stroke of predicted cardioembolic etiology had more prior myocardial infarction and higher CHA2DS2-VASc scores compared to stroke of predicted arterial etiology. Predicted lacunar strokes had higher systolic and diastolic blood pressures and lower NIHSS compared to predicted arterial and cardioembolic strokes. Cryptogenic strokes of unclear predicted etiology were less likely to have a prior TIA or ischemic stroke. Conclusions Gene expression in conjunction with a measure of infarct location can predict a probable cause in cryptogenic strokes. Predicted groups require further evaluation to determine whether relevant clinical, imaging, or therapeutic differences exist for each group. PMID:22627989

A predictive scoring system for insufficient liver hypertrophy after preoperative portal vein embolization.

PubMed

Watanabe, Nobuyuki; Yamamoto, Yusuke; Sugiura, Teiichi; Okamura, Yukiyasu; Ito, Takaaki; Ashida, Ryo; Aramaki, Takeshi; Uesaka, Katsuhiko

2018-05-01

The factors which affect hypertrophy of the future liver remnant after portal vein embolization remain unclear. The aim of this study was to clarify the clinical factors affecting the hypertrophy rate after portal vein embolization and to develop a scoring system predicting insufficient liver hypertrophy. The cases of a total of 152 patients who underwent portal vein embolization of the right portal branch between 2006 and 2016 were reviewed retrospectively. The score to predict insufficient (<25%) hypertrophy was established based on logistic regression analyses of the clinical parameters before portal vein embolization. After portal vein embolization, the future liver remnant volume, expressed as the median (range), significantly increased from 364 (151-801) mL, 33% (18%-54%), to 451 (242-866) mL, 42% (26%-65%). The median hypertrophy rate was 24% (-5% to 96%). A preoperative predictive scoring system for insufficient liver hypertrophy was constructed using the following 3 factors: an initial future liver remnant volume ≥35% (2 points), alkaline phosphatase ≥450 IU/dL (1 point), and cholinesterase <220 mg/dL (1 point). The constructed scoring system indicated the proportion of patients with insufficient liver hypertrophy (<25%) to be 6 out of 42 (14%) in the low-score group (0 points), 44 out of 77 (57%) in the medium-score group (1-2 points), and 30 out of 33 (91%) in the high-score group (3-4 points). The hypertrophy rate of future liver remnant was different among the 3 groups (low-score group, 38.9% [-2.4% to 81.4%]; medium-score group, 22.7% [-5.1% to 95.5%]; high-score group, 18.2% [2.4%-30.7%]) (P < .001). The constructed scoring system was able to stratify patients before portal vein embolization according to the possibility of developing insufficient liver hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of the breast milk expression experience measure.

PubMed

Flaherman, Valerie J; Gay, Barbara; Scott, Cheryl; Aby, Janelle; Stewart, Anita L; Lee, Kathryn A

2013-07-01

Exclusive breastfeeding provides optimal nutrition through 6 months. Recent research has shown that milk expression may affect breastfeeding duration. A woman's experience with milk expression might mediate the effect of milk expression on breastfeeding duration. The objective of this study was to develop a measure to evaluate women's experiences of expressing milk. Based on the available literature, we developed a brief measure of the Breast Milk Expression Experience (BMEE) assessing three dimensions: (1) social support for milk expression; (2) ease of learning how to express milk; and (3) personal experiences of milk expression. All items used 1-5 Likert scales, with higher scores indicating better experiences. We administered the items immediately after expression to 68 mothers who expressed milk post-partum. We evaluated this measure for reliability using Cronbach's alpha. Mothers completing the BMEE were 57% primiparous with 75% vaginal births. The BMEE demonstrated appropriate reliability with a Cronbach's alpha of 0.703 for the summary index and 0.719-0.763 for social support, learning experience and personal experience subscales. The BMEE also indicated good predictive validity; of the six mothers who had a mean score <3 on the 11-item scale post-partum, two (33.3%) were expressing breast milk at 1 month, compared with 37 (80.4%) of the 46 mothers who had a mean score ≥3 on the 11-item scale post-partum (P = 0.012). The BMEE is a promising measure of milk expression experience in this population. Use of this measure may allow improved understanding of women's experiences expressing milk. © 2012 John Wiley & Sons Ltd.

[Circulating miR-152 helps early prediction of postoperative biochemical recurrence of prostate cancer].

PubMed

Chen, Jun-Feng; Liao, Yu-Feng; Ma, Jian-Bo; Mao, Qi-Feng; Jia, Guang-Cheng; Dong, Xue-Jun

2017-07-01

To investigate the value of circulating miR-152 in the early prediction of postoperative biochemical recurrence of prostate cancer. Sixty-six cases of prostate cancer were included in this study, 35 with and 31 without biochemical recurrence within two years postoperatively, and another 31 healthy individuals were enrolled as normal controls. The relative expression levels of circulating miR-152 in the serum of the subjects were detected by qRT-PCR, its value in the early diagnosis of postoperative biochemical recurrence of prostate cancer was assessed by ROC curve analysis, and the correlation of its expression level with the clinicopathological parameters of the patients were analyzed. The expression of circulating miR-152 was significantly lower in the serum of the prostate cancer patients than in the normal controls (t = －5.212, P = 0.001), and so was it in the patients with than in those without postoperative biochemical recurrence (t = －5.727, P = 0.001). The ROC curve for the value of miR-152 in the early prediction of postoperative biochemical recurrence of prostate cancer showed the area under the curve (AUC) to be 0.906 (95% CI: 0.809－0.964), with a sensitivity of 91.4% and a specificity of 80.6%. The expression level of miR-152 was correlated with the Gleason score, clinical stage of prostate cancer, biochemical recurrence, and bone metastasis (P <0.05), decreasing with increased Gleason scores and elevated clinical stage of the malignancy. No correlation, however, was found between the miR-152 expression and the patients' age or preoperative PSA level (P >0.05). The expression level of circulating miR-152 is significantly reduced in prostate cancer patients with biochemical recurrence after prostatectomy and could be a biomarker in the early prediction of postoperative biochemical recurrence of the malignancy.

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia.

PubMed

Yan, Han; Wen, Lu; Tan, Dan; Xie, Pan; Pang, Feng-Mei; Zhou, Hong-Hao; Zhang, Wei; Liu, Zhao-Qian; Tang, Jie; Li, Xi; Chen, Xiao-Ping

2017-01-03

The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10-4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

PubMed Central

Yan, Han; Wen, Lu; Tan, Dan; Xie, Pan; Pang, Feng-mei; Zhou, Hong-hao; Zhang, Wei; Liu, Zhao-qian; Tang, Jie; Li, Xi; Chen, Xiao-ping

2017-01-01

The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10−4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis. PMID:27903973

Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial.

PubMed

Siano, Marco; Espeli, Vittoria; Mach, Nicolas; Bossi, Paolo; Licitra, Lisa; Ghielmini, Michele; Frattini, Milo; Canevari, Silvana; De Cecco, Loris

2018-07-01

Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy. Whole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy. Cluster3 expression levels had a profile with a significant bimodal separation of samples (P =  3.08 E-13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877). Despite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting. Copyright © 2018 Elsevier Ltd. All rights reserved.

Crowdsourcing scoring of immunohistochemistry images: Evaluating Performance of the Crowd and an Automated Computational Method

NASA Astrophysics Data System (ADS)

Irshad, Humayun; Oh, Eun-Yeong; Schmolze, Daniel; Quintana, Liza M.; Collins, Laura; Tamimi, Rulla M.; Beck, Andrew H.

2017-02-01

The assessment of protein expression in immunohistochemistry (IHC) images provides important diagnostic, prognostic and predictive information for guiding cancer diagnosis and therapy. Manual scoring of IHC images represents a logistical challenge, as the process is labor intensive and time consuming. Since the last decade, computational methods have been developed to enable the application of quantitative methods for the analysis and interpretation of protein expression in IHC images. These methods have not yet replaced manual scoring for the assessment of IHC in the majority of diagnostic laboratories and in many large-scale research studies. An alternative approach is crowdsourcing the quantification of IHC images to an undefined crowd. The aim of this study is to quantify IHC images for labeling of ER status with two different crowdsourcing approaches, image-labeling and nuclei-labeling, and compare their performance with automated methods. Crowdsourcing- derived scores obtained greater concordance with the pathologist interpretations for both image-labeling and nuclei-labeling tasks (83% and 87%), as compared to the pathologist concordance achieved by the automated method (81%) on 5,338 TMA images from 1,853 breast cancer patients. This analysis shows that crowdsourcing the scoring of protein expression in IHC images is a promising new approach for large scale cancer molecular pathology studies.

Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

PubMed

Tchetina, Elena V; Demidova, Natalia V; Markova, Galina A; Taskina, Elena A; Glukhova, Svetlana I; Karateev, Dmitry E

2017-10-01

To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Automated Assessment of Child Vocalization Development Using LENA.

PubMed

Richards, Jeffrey A; Xu, Dongxin; Gilkerson, Jill; Yapanel, Umit; Gray, Sharmistha; Paul, Terrance

2017-07-12

To produce a novel, efficient measure of children's expressive vocal development on the basis of automatic vocalization assessment (AVA), child vocalizations were automatically identified and extracted from audio recordings using Language Environment Analysis (LENA) System technology. Assessment was based on full-day audio recordings collected in a child's unrestricted, natural language environment. AVA estimates were derived using automatic speech recognition modeling techniques to categorize and quantify the sounds in child vocalizations (e.g., protophones and phonemes). These were expressed as phone and biphone frequencies, reduced to principal components, and inputted to age-based multiple linear regression models to predict independently collected criterion-expressive language scores. From these models, we generated vocal development AVA estimates as age-standardized scores and development age estimates. AVA estimates demonstrated strong statistical reliability and validity when compared with standard criterion expressive language assessments. Automated analysis of child vocalizations extracted from full-day recordings in natural settings offers a novel and efficient means to assess children's expressive vocal development. More research remains to identify specific mechanisms of operation.

Cross-Language Associations in the Development of Preschoolers’ Receptive and Expressive Vocabulary

PubMed Central

Maier, Michelle F.; Bohlmann, Natalie L.; Palacios, Natalia A.

2016-01-01

The increasing population of dual language learners (DLLs) entering preschool classrooms highlights a continued need for research on the development of dual language acquisition, and specifically vocabulary skills, in this age group. This study describes young DLL children's (N = 177) vocabulary development in both English and Spanish simultaneously, and how vocabulary skills in each language relate to one another, during a contextual shift that places greater emphasis on the acquisition of academic English language skills. Findings demonstrated that DLL preschoolers made gains in vocabulary in both languages with more change evidenced in receptive, in comparison to expressive, vocabulary as well as in English in comparison to Spanish. When examining whether children's vocabulary scores in one language at the beginning of preschool interact with their vocabulary scores in the other language to predict vocabulary growth, no significant associations were found for receptive vocabulary. In contrast, the interaction between initial English and Spanish expressive vocabulary scores was negatively related to growth in English expressive vocabulary. This cross-language association suggests that children who have low expressive vocabulary skills in both languages tend to grow faster in their English expressive vocabulary. The study extends previous work on dual language development by examining growth in expressive and receptive vocabulary in both English and Spanish. It also provides suggestions for future work to inform a more comprehensive understanding of DLL children's development in both languages. PMID:26807002

Cross-Language Associations in the Development of Preschoolers' Receptive and Expressive Vocabulary.

PubMed

Maier, Michelle F; Bohlmann, Natalie L; Palacios, Natalia A

The increasing population of dual language learners (DLLs) entering preschool classrooms highlights a continued need for research on the development of dual language acquisition, and specifically vocabulary skills, in this age group. This study describes young DLL children's ( N = 177) vocabulary development in both English and Spanish simultaneously, and how vocabulary skills in each language relate to one another, during a contextual shift that places greater emphasis on the acquisition of academic English language skills. Findings demonstrated that DLL preschoolers made gains in vocabulary in both languages with more change evidenced in receptive, in comparison to expressive, vocabulary as well as in English in comparison to Spanish. When examining whether children's vocabulary scores in one language at the beginning of preschool interact with their vocabulary scores in the other language to predict vocabulary growth, no significant associations were found for receptive vocabulary. In contrast, the interaction between initial English and Spanish expressive vocabulary scores was negatively related to growth in English expressive vocabulary. This cross-language association suggests that children who have low expressive vocabulary skills in both languages tend to grow faster in their English expressive vocabulary. The study extends previous work on dual language development by examining growth in expressive and receptive vocabulary in both English and Spanish. It also provides suggestions for future work to inform a more comprehensive understanding of DLL children's development in both languages.

A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis: a retrospective, multicenter observational study.

PubMed

Nakagawa, Jin; Koyama, Yoshinobu; Kawakami, Atsushi; Ueki, Yukitaka; Tsukamoto, Hiroshi; Horiuchi, Takahiko; Nagano, Shuji; Uchino, Ayumi; Ota, Toshiyuki; Akahoshi, Mitsuteru; Akashi, Koichi

2017-08-11

Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i. The expression of IL-6 and TNF-α mRNA in peripheral blood from 45 newly diagnosed RA patients was measured by DNA microarrays to evaluate cytokine activation. Next, laboratory indices immediately before commencing treatment and disease activity score improvement ratio after 6 months in 98 patients treated with TCZ or TNF-i were retrospectively analyzed. Some indices correlated with TCZ efficacy were selected and their cutoff values were defined by receiver operating characteristic (ROC) analysis to develop a scoring system to discriminate between individuals more likely to respond to TCZ or TNF-i. The validity of the scoring system was verified in these 98 patients and an additional 228 patients. There was significant inverse correlation between the expression of IL-6 and TNF-α mRNA in newly diagnosed RA patients. The analysis of 98 patients revealed significant correlation between TCZ efficacy and platelet counts, hemoglobin, aspartate aminotransferase, and alanine aminotransferase; in contrast, there was no similar correlation in the TNF-i group. The cutoff values were defined by ROC analysis to develop a scoring system (1 point/item, maximum of 4 points). A good TCZ response was predicted if the score was ≥2; in contrast, TNF-i seemed to be preferable if the score was ≤1. Similar results were obtained in a validation study of an additional 228 patients. If the case scored ≥3, the good responder rates of TCZ/TNF-i were 75.0%/37.9% (p < 0.01) and the non-responder rates were 3.1%/27.6% (p < 0.01), respectively. The score is easily calculated from common laboratory results. It appears useful for identifying a better treatment at the time of selecting either an IL-6 or a TNF inhibitor.

Cultural and Gender Differences in Experiences and Expression of Test Anxiety among Chinese, Finnish, and Swedish Grade 3 Pupils

ERIC Educational Resources Information Center

Nyroos, Mikaela; Korhonen, Johan; Peng, Aihui; Linnanmäki, Karin; Svens-Liavåg, Camilla; Bagger, Anette; Sjöberg, Gunnar

2015-01-01

While test anxiety has been studied extensively, little consideration has been given to the cultural impacts of children's experiences and expressions of test anxiety. The aim of this work was to examine whether variance in test anxiety scores can be predicted based on gender and cultural setting. Three hundred and ninety-eight pupils in Grade 3…

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

PubMed

Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

2017-09-01

To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number of dutch-early-nurse-worry-indicator-score indicators showed higher positive predictive values. Dutch-early-nurse-worry-indicator-score indicators alert in an early stage of deterioration, before reaching the trigger threshold to call a rapid response team and can improve interdisciplinary communication on surgical wards during regular rounds, and when calling for assistance. Dutch-early-nurse-worry-indicator-score structures communication and recording of signs known to be associated with a decline in a patient's condition and can empower nurses to call assistance on the 'worry' criterion in an early stage of deterioration. © 2016 John Wiley & Sons Ltd.

Novel Modeling of Combinatorial miRNA Targeting Identifies SNP with Potential Role in Bone Density

PubMed Central

Coronnello, Claudia; Hartmaier, Ryan; Arora, Arshi; Huleihel, Luai; Pandit, Kusum V.; Bais, Abha S.; Butterworth, Michael; Kaminski, Naftali; Stormo, Gary D.; Oesterreich, Steffi; Benos, Panayiotis V.

2012-01-01

MicroRNAs (miRNAs) are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting), a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD) in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential tool for miRNA-related studies. PMID:23284279

A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.

PubMed

Voyle, Nicola; Keohane, Aoife; Newhouse, Stephen; Lunnon, Katie; Johnston, Caroline; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Hodges, Angela; Kiddle, Steven; Dobson, Richard Jb

2016-01-01

Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. Gene and pathway level models performed similarly to each other and to a model based on demographic information only. Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach.

Cognitive performance predicts treatment decisional abilities in mild to moderate dementia.

PubMed

Gurrera, R J; Moye, J; Karel, M J; Azar, A R; Armesto, J C

2006-05-09

To examine the contribution of neuropsychological test performance to treatment decision-making capacity in community volunteers with mild to moderate dementia. The authors recruited volunteers (44 men, 44 women) with mild to moderate dementia from the community. Subjects completed a battery of 11 neuropsychological tests that assessed auditory and visual attention, logical memory, language, and executive function. To measure decision making capacity, the authors administered the Capacity to Consent to Treatment Interview, the Hopemont Capacity Assessment Interview, and the MacCarthur Competence Assessment Tool--Treatment. Each of these instruments individually scores four decisional abilities serving capacity: understanding, appreciation, reasoning, and expression of choice. The authors used principal components analysis to generate component scores for each ability across instruments, and to extract principal components for neuropsychological performance. Multiple linear regression analyses demonstrated that neuropsychological performance significantly predicted all four abilities. Specifically, it predicted 77.8% of the common variance for understanding, 39.4% for reasoning, 24.6% for appreciation, and 10.2% for expression of choice. Except for reasoning and appreciation, neuropsychological predictor (beta) profiles were unique for each ability. Neuropsychological performance substantially and differentially predicted capacity for treatment decisions in individuals with mild to moderate dementia. Relationships between elemental cognitive function and decisional capacity may differ in individuals whose decisional capacity is impaired by other disorders, such as mental illness.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

PubMed

Beyene, Desta A; Naab, Tammey J; Kanarek, Norma F; Apprey, Victor; Esnakula, Ashwini; Khan, Farahan A; Blackman, Marc R; Brown, Collis A; Hudson, Tamaro S

2018-08-01

Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5). AA men aged 41-90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2-6 and HSP60 differed between GS 7 and GS 2-6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men. © 2018 Wiley Periodicals, Inc.

ERβ Expression and Breast Cancer Risk Prediction for Women with Atypias

PubMed Central

Hieken, Tina J; Carter, Jodi M; Hawse, John R; Hoskin, Tanya L; Bois, Melanie; Frost, Marlene; Hartmann, Lynn C; Radisky, Derek C; Visscher, Daniel W; Degnim, Amy C

2015-01-01

Estrogen receptor beta (ERβ) is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171 women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15 years median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules than normal lobules, by percent staining and intensity (both p<0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2 (p=0.04) and 2.5-fold (p=0.006). High normal lobule ERβ expression conferred the strongest protective effect in pre-menopausal women: the 20-year cumulative incidence of breast cancer was 0% for women

Spoken language development in children following cochlear implantation.

PubMed

Niparko, John K; Tobey, Emily A; Thal, Donna J; Eisenberg, Laurie S; Wang, Nae-Yuh; Quittner, Alexandra L; Fink, Nancy E

2010-04-21

Cochlear implantation is a surgical alternative to traditional amplification (hearing aids) that can facilitate spoken language development in young children with severe to profound sensorineural hearing loss (SNHL). To prospectively assess spoken language acquisition following cochlear implantation in young children. Prospective, longitudinal, and multidimensional assessment of spoken language development over a 3-year period in children who underwent cochlear implantation before 5 years of age (n = 188) from 6 US centers and hearing children of similar ages (n = 97) from 2 preschools recruited between November 2002 and December 2004. Follow-up completed between November 2005 and May 2008. Performance on measures of spoken language comprehension and expression (Reynell Developmental Language Scales). Children undergoing cochlear implantation showed greater improvement in spoken language performance (10.4; 95% confidence interval [CI], 9.6-11.2 points per year in comprehension; 8.4; 95% CI, 7.8-9.0 in expression) than would be predicted by their preimplantation baseline scores (5.4; 95% CI, 4.1-6.7, comprehension; 5.8; 95% CI, 4.6-7.0, expression), although mean scores were not restored to age-appropriate levels after 3 years. Younger age at cochlear implantation was associated with significantly steeper rate increases in comprehension (1.1; 95% CI, 0.5-1.7 points per year younger) and expression (1.0; 95% CI, 0.6-1.5 points per year younger). Similarly, each 1-year shorter history of hearing deficit was associated with steeper rate increases in comprehension (0.8; 95% CI, 0.2-1.2 points per year shorter) and expression (0.6; 95% CI, 0.2-1.0 points per year shorter). In multivariable analyses, greater residual hearing prior to cochlear implantation, higher ratings of parent-child interactions, and higher socioeconomic status were associated with greater rates of improvement in comprehension and expression. The use of cochlear implants in young children was associated with better spoken language learning than would be predicted from their preimplantation scores.

Docking and scoring protein complexes: CAPRI 3rd Edition.

PubMed

Lensink, Marc F; Méndez, Raúl; Wodak, Shoshana J

2007-12-01

The performance of methods for predicting protein-protein interactions at the atomic scale is assessed by evaluating blind predictions performed during 2005-2007 as part of Rounds 6-12 of the community-wide experiment on Critical Assessment of PRedicted Interactions (CAPRI). These Rounds also included a new scoring experiment, where a larger set of models contributed by the predictors was made available to groups developing scoring functions. These groups scored the uploaded set and submitted their own best models for assessment. The structures of nine protein complexes including one homodimer were used as targets. These targets represent biologically relevant interactions involved in gene expression, signal transduction, RNA, or protein processing and membrane maintenance. For all the targets except one, predictions started from the experimentally determined structures of the free (unbound) components or from models derived by homology, making it mandatory for docking methods to model the conformational changes that often accompany association. In total, 63 groups and eight automatic servers, a substantial increase from previous years, submitted docking predictions, of which 1994 were evaluated here. Fifteen groups submitted 305 models for five targets in the scoring experiment. Assessment of the predictions reveals that 31 different groups produced models of acceptable and medium accuracy-but only one high accuracy submission-for all the targets, except the homodimer. In the latter, none of the docking procedures reproduced the large conformational adjustment required for correct assembly, underscoring yet again that handling protein flexibility remains a major challenge. In the scoring experiment, a large fraction of the groups attained the set goal of singling out the correct association modes from incorrect solutions in the limited ensembles of contributed models. But in general they seemed unable to identify the best models, indicating that current scoring methods are probably not sensitive enough. With the increased focus on protein assemblies, in particular by structural genomics efforts, the growing community of CAPRI predictors is engaged more actively than ever in the development of better scoring functions and means of modeling conformational flexibility, which hold promise for much progress in the future. (c) 2007 Wiley-Liss, Inc.

Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis

PubMed Central

Hitchon, Carol

2017-01-01

Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies. PMID:28572711

Whole blood gene expression testing for coronary artery disease in nondiabetic patients: major adverse cardiovascular events and interventions in the PREDICT trial.

PubMed

Rosenberg, Steven; Elashoff, Michael R; Lieu, Hsiao D; Brown, Bradley O; Kraus, William E; Schwartz, Robert S; Voros, Szilard; Ellis, Stephen G; Waksman, Ron; McPherson, John A; Lansky, Alexandra J; Topol, Eric J

2012-06-01

The majority of first-time angiography patients are without obstructive coronary artery disease (CAD). A blood gene expression score (GES) for obstructive CAD likelihood was validated in the PREDICT study, but its relation to major adverse cardiovascular events (MACE) and revascularization was not assessed. Patients (N = 1,160) were followed up for MACE and revascularization 1 year post-index angiography and GES, with 1,116 completing follow-up. The 30-day event rate was 23% and a further 2.2% at 12 months. The GES was associated with MACE/revascularizations (p < 0.001) and added to clinical risk scores. Patients with GES >15 trended towards increased >30 days MACE/revascularization likelihood (odds ratio = 2.59, 95% confidence interval = 0.89-9.14, p = 0.082). MACE incidence overall was 1.5% (17 of 1,116) and 3 of 17 patients had GES ≤ 15. For the total low GES group (N = 396), negative predictive value was 90% for MACE/revascularization and >99% for MACE alone, identifying a group of patients without obstructive CAD and highly unlikely to suffer MACE within 12 months.

Establishment of a 12-gene expression signature to predict colon cancer prognosis

PubMed Central

Zhao, Guangxi; Dong, Pingping; Wu, Bingrui

2018-01-01

A robust and accurate gene expression signature is essential to assist oncologists to determine which subset of patients at similar Tumor-Lymph Node-Metastasis (TNM) stage has high recurrence risk and could benefit from adjuvant therapies. Here we applied a two-step supervised machine-learning method and established a 12-gene expression signature to precisely predict colon adenocarcinoma (COAD) prognosis by using COAD RNA-seq transcriptome data from The Cancer Genome Atlas (TCGA). The predictive performance of the 12-gene signature was validated with two independent gene expression microarray datasets: GSE39582 includes 566 COAD cases for the development of six molecular subtypes with distinct clinical, molecular and survival characteristics; GSE17538 is a dataset containing 232 colon cancer patients for the generation of a metastasis gene expression profile to predict recurrence and death in COAD patients. The signature could effectively separate the poor prognosis patients from good prognosis group (disease specific survival (DSS): Kaplan Meier (KM) Log Rank p = 0.0034; overall survival (OS): KM Log Rank p = 0.0336) in GSE17538. For patients with proficient mismatch repair system (pMMR) in GSE39582, the signature could also effectively distinguish high risk group from low risk group (OS: KM Log Rank p = 0.005; Relapse free survival (RFS): KM Log Rank p = 0.022). Interestingly, advanced stage patients were significantly enriched in high 12-gene score group (Fisher’s exact test p = 0.0003). After stage stratification, the signature could still distinguish poor prognosis patients in GSE17538 from good prognosis within stage II (Log Rank p = 0.01) and stage II & III (Log Rank p = 0.017) in the outcome of DFS. Within stage III or II/III pMMR patients treated with Adjuvant Chemotherapies (ACT) and patients with higher 12-gene score showed poorer prognosis (III, OS: KM Log Rank p = 0.046; III & II, OS: KM Log Rank p = 0.041). Among stage II/III pMMR patients with lower 12-gene scores in GSE39582, the subgroup receiving ACT showed significantly longer OS time compared with those who received no ACT (Log Rank p = 0.021), while there is no obvious difference between counterparts among patients with higher 12-gene scores (Log Rank p = 0.12). Besides COAD, our 12-gene signature is multifunctional in several other cancer types including kidney cancer, lung cancer, uveal and skin melanoma, brain cancer, and pancreatic cancer. Functional classification showed that seven of the twelve genes are involved in immune system function and regulation, so our 12-gene signature could potentially be used to guide decisions about adjuvant therapy for patients with stage II/III and pMMR COAD.

The relationship between insight and the level of expressed emotion in patients with obsessive-compulsive disorder.

PubMed

Ozkiris, Ayse; Essizoglu, Altan; Gulec, Gulcan; Aksaray, Gokay

2015-04-01

The aim of this study is firstly to compare the obsessive-compulsive disorder (OCD) patients with good insight and OCD patients with poor insight in terms of socio-demographic and clinical features; to investigate the relation between insight and the level of the expressed emotion (EE) in the patients; and lastly to specify the factors that predict level of insight. OCD patients with good insight and patients with poor insight were compared in terms of clinical features and the perceived EE level of the patients and the individuals that they live with in order to specify the factors that predict the insight level, and to investigate the relationship between insight level and EE. It was found that the total Expressed Emotion Scale, total Level of Expressed Emotion (LEE), LEE-Emotional Response and LEE-Tolerance/Expectation subscale scores of the group comprised of patients with poor insight are higher than the other group. The results also show that the duration of illness and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score predict insight level. This study shows that the level of EE perceived by the patients with poor insight and the person that he/she lives with, is higher than the group with good insight. The studies that investigate the relationship between the factors of insight level and EE level, which are indicated to determine the level of the illness severity and its chronicity, will enable the researchers to understand the importance of the role of the family on the treatment processes of OCD.

Expression profiles of loneliness-associated genes for survival prediction in cancer patients.

PubMed

You, Liang-Fu; Yeh, Jia-Rong; Su, Mu-Chun

2014-01-01

Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high- lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness- associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.

A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes.

PubMed

Mehdi, Ahmed M; Hamilton-Williams, Emma E; Cristino, Alexandre; Ziegler, Anette; Bonifacio, Ezio; Le Cao, Kim-Anh; Harris, Mark; Thomas, Ranjeny

2018-03-08

Autoimmune-mediated destruction of pancreatic islet β cells results in type 1 diabetes (T1D). Serum islet autoantibodies usually develop in genetically susceptible individuals in early childhood before T1D onset, with multiple islet autoantibodies predicting diabetes development. However, most at-risk children remain islet-antibody negative, and no test currently identifies those likely to seroconvert. We sought a genomic signature predicting seroconversion risk by integrating longitudinal peripheral blood gene expression profiles collected in high-risk children included in the BABYDIET and DIPP cohorts, of whom 50 seroconverted. Subjects were followed for 10 years to determine time of seroconversion. Any cohort effect and the time of seroconversion were corrected to uncover genes differentially expressed (DE) in seroconverting children. Gene expression signatures associated with seroconversion were evident during the first year of life, with 67 DE genes identified in seroconverting children relative to those remaining antibody negative. These genes contribute to T cell-, DC-, and B cell-related immune responses. Near-birth expression of ADCY9, PTCH1, MEX3B, IL15RA, ZNF714, TENM1, and PLEKHA5, along with HLA risk score predicted seroconversion (AUC 0.85). The ubiquitin-proteasome pathway linked DE genes and T1D susceptibility genes. Therefore, a gene expression signature in infancy predicts risk of seroconversion. Ubiquitination may play a mechanistic role in diabetes progression.

A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes

PubMed Central

Mehdi, Ahmed M.; Hamilton-Williams, Emma E.; Cristino, Alexandre; Ziegler, Anette; Harris, Mark

2018-01-01

Autoimmune-mediated destruction of pancreatic islet β cells results in type 1 diabetes (T1D). Serum islet autoantibodies usually develop in genetically susceptible individuals in early childhood before T1D onset, with multiple islet autoantibodies predicting diabetes development. However, most at-risk children remain islet-antibody negative, and no test currently identifies those likely to seroconvert. We sought a genomic signature predicting seroconversion risk by integrating longitudinal peripheral blood gene expression profiles collected in high-risk children included in the BABYDIET and DIPP cohorts, of whom 50 seroconverted. Subjects were followed for 10 years to determine time of seroconversion. Any cohort effect and the time of seroconversion were corrected to uncover genes differentially expressed (DE) in seroconverting children. Gene expression signatures associated with seroconversion were evident during the first year of life, with 67 DE genes identified in seroconverting children relative to those remaining antibody negative. These genes contribute to T cell–, DC-, and B cell–related immune responses. Near-birth expression of ADCY9, PTCH1, MEX3B, IL15RA, ZNF714, TENM1, and PLEKHA5, along with HLA risk score predicted seroconversion (AUC 0.85). The ubiquitin-proteasome pathway linked DE genes and T1D susceptibility genes. Therefore, a gene expression signature in infancy predicts risk of seroconversion. Ubiquitination may play a mechanistic role in diabetes progression. PMID:29515040

Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.

PubMed

Marigorta, Urko M; Denson, Lee A; Hyams, Jeffrey S; Mondal, Kajari; Prince, Jarod; Walters, Thomas D; Griffiths, Anne; Noe, Joshua D; Crandall, Wallace V; Rosh, Joel R; Mack, David R; Kellermayer, Richard; Heyman, Melvin B; Baker, Susan S; Stephens, Michael C; Baldassano, Robert N; Markowitz, James F; Kim, Mi-Ok; Dubinsky, Marla C; Cho, Judy; Aronow, Bruce J; Kugathasan, Subra; Gibson, Greg

2017-10-01

Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus protection, thereby linking statistical association to biological mechanism. The TRS approach constitutes a potential strategy for personalized medicine that enhances inference from static genotypic risk assessment.

Prediction With Dimension Reduction of Multiple Molecular Data Sources for Patient Survival.

PubMed

Kaplan, Adam; Lock, Eric F

2017-01-01

Predictive modeling from high-dimensional genomic data is often preceded by a dimension reduction step, such as principal component analysis (PCA). However, the application of PCA is not straightforward for multisource data, wherein multiple sources of 'omics data measure different but related biological components. In this article, we use recent advances in the dimension reduction of multisource data for predictive modeling. In particular, we apply exploratory results from Joint and Individual Variation Explained (JIVE), an extension of PCA for multisource data, for prediction of differing response types. We conduct illustrative simulations to illustrate the practical advantages and interpretability of our approach. As an application example, we consider predicting survival for patients with glioblastoma multiforme from 3 data sources measuring messenger RNA expression, microRNA expression, and DNA methylation. We also introduce a method to estimate JIVE scores for new samples that were not used in the initial dimension reduction and study its theoretical properties; this method is implemented in the R package R.JIVE on CRAN, in the function jive.predict.

Abdominal pain and the neurotrophic system in ulcerative colitis.

PubMed

Deberry, Jennifer J; Bielefeldt, Klaus; Davis, Brian M; Szigethy, Eva M; Hartman, Douglas J; Coates, Matthew D

2014-12-01

We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC). Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, IL-17). A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5). We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation.

Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: A Multi-Site, Blinded Validation Study

PubMed Central

Shedden, Kerby; Taylor, Jeremy M.G.; Enkemann, Steve A.; Tsao, Ming S.; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steve; Jurisica, Igor; Venkatraman, Seshan E.; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang Qi; Strumpf, Dan; Hanash, Samir; Shepherd, Francis A.; Ding, Kuyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan; Weir, Barbara; Verhaak, Roel; Ladd-Acosta, Christine; Golub, Todd; Gruidl, Mike; Szoke, Janos; Zakowski, Maureen; Rusch, Valerie; Kris, Mark; Viale, Agnes; Motoi, Noriko; Travis, William; Sharma, Anupama

2009-01-01

Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. PMID:18641660

Digital image analysis improves precision of programmed death ligand 1 (PD-L1) scoring in cutaneous melanoma.

PubMed

Koelzer, Viktor H; Gisler, Aline; Hanhart, Jonathan C; Griss, Johannes; Wagner, Stephan N; Willi, Niels; Cathomas, Gieri; Sachs, Melanie; Kempf, Werner; Thommen, Daniela S; Mertz, Kirsten D

2018-04-16

Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD-L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD-L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardized digital protocol for the assessment of PD-L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists. In two cohorts with a total of 69 cutaneous melanomas, a highly significant correlation was found between pathologist-based consensus reading and automated PD-L1 analysis (R=0.97, p<0.0001). Digital scoring captured the full diagnostic spectrum of PD-L1 expression at single cell resolution. An average of 150.472 melanoma cells (median 38.668 cells; range 733-1.078.965) were scored per lesion. Machine learning was used to control for heterogeneity introduced by PD-L1 positive inflammatory cells in the tumour microenvironment. The PD-L1 image analysis protocol showed excellent reproducibility (R=1.0, p<0.0001) when carried out on independent workstations and reduced variability in PD-L1 scoring of human observers. When melanomas were grouped by PD-L1 expression status, we found a clear correlation of PD-L1 positivity with CD8 positive T-cell infiltration, but not with tumour stage, metastasis or driver mutation status. Digital evaluation of PD-L1 reduces scoring variability and may facilitate patient stratification in clinical practice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Plasma concentration of diamine oxidase (DAO) predicts 1-month mortality of acute-on-chronic hepatitis B liver failure.

PubMed

Li, Feng-Cai; Li, Yue-Kai; Fan, Yu-Chen; Wang, Kai

2018-05-26

Acute-on-chronic hepatitis B liver failure (ACHBLF) has high 1-month mortality but it is difficult to predict. This present study was aimed to determine the diagnostic value of plasma diamine oxidase (DAO) in predicting the 1-month mortality of ACHBLF. A total of 106 consecutive newly diagnosed ACHBLF patients were retrospectively collected. The plasma expression of DAO was determined using enzyme-linked immunosorbent assay (ELISA). The plasma DAO level of survivals [14.0 (7.1; 26.5) ng/mL] was significantly lower than the nonsurvivals [58.6 (32.5; 121.3) ng/mL, P < .001]. The plasma DAO level, hepatic encephalopathy, spontaneous bacterial peritonitis and model for end-stage liver disease (MELD) score were independent factors associated with the 1-month mortality for ACHBLF. The cut-off point of 15.2 ng/mL for plasma DAO level with sensitivity of 95.45%, specificity of 62.5%, 22.6 for MELD score with sensitivity of 90.91%, specificity of 67.5%, 0.07 for DAO plus MELD with sensitivity of 87.88%, specificity of 80% were selected to discriminate 1-month morality of ACHBLF. Furthermore, DAO plus MELD score showed high AUROC than MELD score for predicting 1-month (0.916 vs. 0.843, P < .01). The plasma DAO level plus MELD > 0.07 predicts poor 1-month mortality of ACHBLF. Copyright © 2018 Elsevier B.V. All rights reserved.

Performance of polygenic scores for predicting phobic anxiety.

PubMed

Walter, Stefan; Glymour, M Maria; Koenen, Karestan; Liang, Liming; Tchetgen Tchetgen, Eric J; Cornelis, Marilyn; Chang, Shun-Chiao; Rimm, Eric; Kawachi, Ichiro; Kubzansky, Laura D

2013-01-01

Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20-40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.

Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

PubMed Central

Mazloom, Amin R.; Dannenfelser, Ruth; Clark, Neil R.; Grigoryan, Arsen V.; Linder, Kathryn M.; Cardozo, Timothy J.; Bond, Julia C.; Boran, Aislyn D. W.; Iyengar, Ravi; Malovannaya, Anna; Lanz, Rainer B.; Ma'ayan, Avi

2011-01-01

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/. PMID:22219718

Karolinska Interpersonal Violence Scale predicts suicide in suicide attempters.

PubMed

Jokinen, Jussi; Forslund, Kaj; Ahnemark, Ewa; Gustavsson, J Petter; Nordström, Peter; Asberg, Marie

2010-08-01

Both childhood trauma and violent behavior are important risk factors for suicidal behavior. The aim of the present study was to construct and validate a clinical rating scale that could measure both the exposure to and the expression of violence in childhood and during adult life and to study the ability of the Karolinska Interpersonal Violence Scale (KIVS) to predict ultimate suicide in suicide attempters. A total of 161 suicide attempters and 95 healthy volunteers were assessed with the KIVS measuring exposure to violence and expressed violent behavior in childhood (between 6-14 years of age) and during adult life (15 years or older). The Buss-Durkee Hostility Inventory (BDHI), "Urge to act out hostility" subscale from the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Early Experience Questionnaire (EEQ) were used for validation. All patients were followed up for cause of death and a minimum of 4 years from entering in the study. Five patients who committed suicide within 4 years had significantly higher scores in exposure to violence as a child, in expressed violent behavior as an adult, and in KIVS total score compared to survivors. Suicide attempters scored significantly higher compared to healthy volunteers in 3 of the 4 KIVS subscales. There were significant correlations between the subscales measuring exposure to and expression of violent behavior during the life cycle. BDHI, Urge to act out hostility, and EEQ validated the KIVS. Exposure to violence in childhood and violent behavior in adulthood are risk factors for completed suicide in suicide attempters. Behavioral dysregulation of aggression is important to assess in clinical work. The KIVS is a valuable new tool for case detection and long-term clinical suicide prevention. Copyright 2010 Physicians Postgraduate Press, Inc.

Linking melodic expectation to expressive performance timing and perceived musical tension.

PubMed

Gingras, Bruno; Pearce, Marcus T; Goodchild, Meghan; Dean, Roger T; Wiggins, Geraint; McAdams, Stephen

2016-04-01

This research explored the relations between the predictability of musical structure, expressive timing in performance, and listeners' perceived musical tension. Studies analyzing the influence of expressive timing on listeners' affective responses have been constrained by the fact that, in most pieces, the notated durations limit performers' interpretive freedom. To circumvent this issue, we focused on the unmeasured prelude, a semi-improvisatory genre without notated durations. In Experiment 1, 12 professional harpsichordists recorded an unmeasured prelude on a harpsichord equipped with a MIDI console. Melodic expectation was assessed using a probabilistic model (IDyOM [Information Dynamics of Music]) whose expectations have been previously shown to match closely those of human listeners. Performance timing information was extracted from the MIDI data using a score-performance matching algorithm. Time-series analyses showed that, in a piece with unspecified note durations, the predictability of melodic structure measurably influenced tempo fluctuations in performance. In Experiment 2, another 10 harpsichordists, 20 nonharpsichordist musicians, and 20 nonmusicians listened to the recordings from Experiment 1 and rated the perceived tension continuously. Granger causality analyses were conducted to investigate predictive relations among melodic expectation, expressive timing, and perceived tension. Although melodic expectation, as modeled by IDyOM, modestly predicted perceived tension for all participant groups, neither of its components, information content or entropy, was Granger causal. In contrast, expressive timing was a strong predictor and was Granger causal. However, because melodic expectation was also predictive of expressive timing, our results outline a complete chain of influence from predictability of melodic structure via expressive performance timing to perceived musical tension. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Integrated CLL Scoring System, a New and Simple Index to Predict Time to Treatment and Overall Survival in Patients With Chronic Lymphocytic Leukemia.

PubMed

Visentin, Andrea; Facco, Monica; Frezzato, Federica; Castelli, Monica; Trimarco, Valentina; Martini, Veronica; Gattazzo, Cristina; Severin, Filippo; Chiodin, Giorgia; Martines, Annalisa; Bonaldi, Laura; Gianesello, Ilaria; Pagnin, Elisa; Boscaro, Elisa; Piazza, Francesco; Zambello, Renato; Semenzato, Gianpietro; Trentin, Livio

2015-10-01

Several prognostic factors have been identified to predict the outcome of patients with chronic lymphocytic leukemia (CLL), but only a few studies analyzed more markers together. Taking advantage of a population of 608 patients, we identified the strongest prognostic markers of survival and, subsequently, in a cohort of 212 patients we integrated data of cytogenetic lesions, IGHV mutational status, and CD38 expression in a new and easy scoring system we called the integrated CLL scoring system (ICSS). ICSS defines 3 groups of risk: (1) low risk (patients with 13q(-) or normal fluorescence in-situ hybridization analysis results, mutated IGHV, and CD38) (2) high risk (all 11q(-) or 17p(-) patients and/or all unmutated IGHV and CD38(+) patients); and (3) intermediate risk (all remaining patients). Using only these 3 already available prognostic factors, we were able to properly redefine patients and better predict the clinical course of the disease. ICSS could become a useful tool for CLL patients' management. Copyright © 2015 Elsevier Inc. All rights reserved.

High Anger Expression is Associated with Reduced Cortisol Awakening Response and Health Complaints in Healthy Young Adults.

PubMed

Romero-Martínez, Ángel; Moya-Albiol, Luis

2016-04-29

The extant evidence suggests a robust positive association between expression (anger expression-out) and suppression (anger expression-in) of anger and compromised health. Nevertheless, the underlying psychobiological mechanisms which explain these relationships are not well understood. This study examined whether anger expression would predict general health, cortisol awakening response (CAR) and evening cortisol levels in a community sample of 156 healthy young adults of both genders. Participants were distributed into two groups according to their anger expression scores: high and low anger expression (HAE and LAE, respectively). Findings indicated that those with HAE had worse self-reported health (p = .02) and higher CAR than the LAE group (p = .04). Moreover, high levels of anger expression-out (p < .01) and -in (p < .01, for all) predicted a worse self-reported health in both groups. On the other hand, high anger expression-out was associated with flattened CAR but only in the HAE group (p < .01). This study reinforces the need to develop effective strategies to provide mechanisms to regulate anger expression by promoting personal growth and positive skills that enhance individuals' well-being and quality of life and, in turn, their own health.

ESR1 Promoter Hypermethylation Does Not Predict Atypia in RPFNA nor Persistent Atypia after 12 Months Tamoxifen Chemoprevention

PubMed Central

Baker, Joseph C.; Ostrander, Julie H.; Lem, Siya; Broadwater, Gloria; Bean, Gregory R.; D'Amato, Nicholas C.; Goldenberg, Vanessa K.; Rowell, Craig; Ibarra-Drendall, Catherine; Grant, Tracey; Pilie, Patrick G.; Vasilatos, Shauna N.; Troch, Michelle M.; Scott, Victoria; Wilke, Lee G.; Paisie, Carolyn; Rabiner, Sarah M.; Torres-Hernandez, Alejandro; Zalles, Carola M.; Seewaldt, Victoria L.

2009-01-01

Purpose Currently, we lack biomarkers to predict whether high-risk women with mammary atypia will respond to tamoxifen chemoprevention. Experimental Design Thirty-four women with cytologic mammary atypia from the Duke University High-Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1 promoter hypermethylation and/or estrogen receptor (ER) protein expression by immunohistochemistry predicted persistent atypia in 18 women who were treated with tamoxifen for 12 months and in 16 untreated controls. Results We observed a statistically significant decrease in the Masood score of women on tamoxifen chemoprevention for 12 months compared with control women. This was a significant interaction effect of time (0, 6, and 12 months) and treatment group (tamoxifen versus control) P = 0.0007. However, neither ESR1 promoter hypermethylation nor low ER expression predicted persistent atypia in Random Periareolar Fine Needle Aspiration after 12 months tamoxifen prevention. Conclusions Results from this single institution pilot study provide evidence that, unlike for invasive breast cancer, ESR1 promoter hypermethylation and/or low ER expression is not a reliable marker of tamoxifen-resistant atypia. PMID:18708376

Predicting Intentional Communication in Preverbal Preschoolers with Autism Spectrum Disorder.

PubMed

Sandbank, Micheal; Woynaroski, Tiffany; Watson, Linda R; Gardner, Elizabeth; Keçeli Kaysili, Bahar; Yoder, Paul

2017-06-01

Intentional communication has previously been identified as a value-added predictor of expressive language in preverbal preschoolers with autism spectrum disorder. In the present study, we sought to identify value-added predictors of intentional communication. Of five theoretically-motivated putative predictors of intentional communication measured early in the study (at study entry and 4 months after), three had significant zero-order correlations with later intentional communication (12 months after study entry) and were thus added to a linear model that predicted later intentional communication scores controlling for initial intentional communication scores at study entry. After controlling for initial intentional communication, early motor imitation was the only predictor that accounted for a significant amount of variance in children's later intentional communication.

Interpersonal ambivalence, perceived relationship adjustment, and conjugal loss.

PubMed

Bonanno, G A; Notarius, C I; Gunzerath, L; Keltner, D; Horowitz, M J

1998-12-01

Ambivalence is widely assumed to prolong grief. To examine this hypothesis, the authors developed a measure of ambivalence based on an algorithmic combination of separate positive and negative evaluations of one's spouse. Preliminary construct validity was evidenced in relation to emotional difficulties and to facial expressions of emotion. Bereaved participants, relative to a nonbereaved comparison sample, recollected their relationships as better adjusted but were more ambivalent. Ambivalence about spouses was generally associated with increased distress and poorer perceived health but did not predict long-term grief outcome once initial outcome was controlled. In contrast, initial grief and distress predicted increased ambivalence and decreased Dyadic Adjustment Scale scores at 14 months postloss, regardless of initial scores on these measures. Limitations and implications of the findings are discussed.

Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche

PubMed Central

Tan, Xiaojie; Ding, Yibo; Luo, Yanxin; Cai, Hui; Liu, Yan; Gao, Xianhua; Liu, Qizhi; Yu, Yongwei; Du, Yan; Wang, Hao; Ma, Liye; Wang, Jianping; Chen, Kun; Ding, Yanqing; Fu, Chuangang; Cao, Guangwen

2016-01-01

Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC. PMID:26556874

AUC-based biomarker ensemble with an application on gene scores predicting low bone mineral density.

PubMed

Zhao, X G; Dai, W; Li, Y; Tian, L

2011-11-01

The area under the receiver operating characteristic (ROC) curve (AUC), long regarded as a 'golden' measure for the predictiveness of a continuous score, has propelled the need to develop AUC-based predictors. However, the AUC-based ensemble methods are rather scant, largely due to the fact that the associated objective function is neither continuous nor concave. Indeed, there is no reliable numerical algorithm identifying optimal combination of a set of biomarkers to maximize the AUC, especially when the number of biomarkers is large. We have proposed a novel AUC-based statistical ensemble methods for combining multiple biomarkers to differentiate a binary response of interest. Specifically, we propose to replace the non-continuous and non-convex AUC objective function by a convex surrogate loss function, whose minimizer can be efficiently identified. With the established framework, the lasso and other regularization techniques enable feature selections. Extensive simulations have demonstrated the superiority of the new methods to the existing methods. The proposal has been applied to a gene expression dataset to construct gene expression scores to differentiate elderly women with low bone mineral density (BMD) and those with normal BMD. The AUCs of the resulting scores in the independent test dataset has been satisfactory. Aiming for directly maximizing AUC, the proposed AUC-based ensemble method provides an efficient means of generating a stable combination of multiple biomarkers, which is especially useful under the high-dimensional settings. lutian@stanford.edu. Supplementary data are available at Bioinformatics online.

Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

PubMed

Christenson, Stephanie A; Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S; Postma, Dirkje S; Lenburg, Marc E; Spira, Avrum; Woodruff, Prescott G

2015-04-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease

PubMed Central

Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S.; Postma, Dirkje S.; Lenburg, Marc E.; Spira, Avrum; Woodruff, Prescott G.

2015-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma. PMID:25611785

Cognitive performance predicts treatment decisional abilities in mild to moderate dementia

PubMed Central

Gurrera, R.J.; Moye, J.; Karel, M.J.; Azar, A.R.; Armesto, J.C.

2016-01-01

Objective To examine the contribution of neuropsychological test performance to treatment decision-making capacity in community volunteers with mild to moderate dementia. Methods The authors recruited volunteers (44 men, 44 women) with mild to moderate dementia from the community. Subjects completed a battery of 11 neuropsychological tests that assessed auditory and visual attention, logical memory, language, and executive function. To measure decision making capacity, the authors administered the Capacity to Consent to Treatment Interview, the Hopemont Capacity Assessment Interview, and the MacCarthur Competence Assessment Tool—Treatment. Each of these instruments individually scores four decisional abilities serving capacity: understanding, appreciation, reasoning, and expression of choice. The authors used principal components analysis to generate component scores for each ability across instruments, and to extract principal components for neuropsychological performance. Results Multiple linear regression analyses demonstrated that neuropsychological performance significantly predicted all four abilities. Specifically, it predicted 77.8% of the common variance for understanding, 39.4% for reasoning, 24.6% for appreciation, and 10.2% for expression of choice. Except for reasoning and appreciation, neuropsychological predictor (β) profiles were unique for each ability. Conclusions Neuropsychological performance substantially and differentially predicted capacity for treatment decisions in individuals with mild to moderate dementia. Relationships between elemental cognitive function and decisional capacity may differ in individuals whose decisional capacity is impaired by other disorders, such as mental illness. PMID:16682669

Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.

PubMed

Mannan, Rahul; Bhasin, Tejinder Singh; Manjari, Mridu; Singh, Gagandeep; Bhatia, Puneet Kaur; Sharma, Sonam

2016-01-01

Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product) is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion. Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100) of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. Majority of patients included in the study were in the age group of 61-80 (84% of the total). When ERG expression was studied with age-specific rates, it was not found to be statistically significant. The most common pattern noted in the present study was 4 + 3, constituting 36% of total, followed by 3 + 4 constituting 32%. Calculating the score, the majority of patients had a Gleason score of 5-8, constituting 76% of total. Out of the total fifty cases of prostate carcinoma, ERG was positive in 29 cases (58%) and negative in 21 cases (42%). Fourteen out of 21 (48%) of the ERG positive cases had an intensity score of 3. When the ERG intensity was correlated with the Gleason score group, it was seen that patients having Gleason score 7-8 showed ERG positivity in 19 out of 38 cases (50%), with 11/19 (57%) cases showing an ERG intensity score of 3. The Gleason score group 9-10 showed ERG positivity in 83% (10/12) cases, 20% (2/10) cases showing intensity score of 3. This correlation was found to be statistically significant. ERG immunostaining was performed in a small Indian cohort of prostate cancer patients, diagnosed in trucut biopsy specimens and prostatic chips. ERG expression was found in 58% patients. An increase in the ERG expression was observed with an increase in Gleason score. The intensity of ERG expression, however, decreased with an increasing Gleason score.

Psychometric challenges and proposed solutions when scoring facial emotion expression codes.

PubMed

Olderbak, Sally; Hildebrandt, Andrea; Pinkpank, Thomas; Sommer, Werner; Wilhelm, Oliver

2014-12-01

Coding of facial emotion expressions is increasingly performed by automated emotion expression scoring software; however, there is limited discussion on how best to score the resulting codes. We present a discussion of facial emotion expression theories and a review of contemporary emotion expression coding methodology. We highlight methodological challenges pertinent to scoring software-coded facial emotion expression codes and present important psychometric research questions centered on comparing competing scoring procedures of these codes. Then, on the basis of a time series data set collected to assess individual differences in facial emotion expression ability, we derive, apply, and evaluate several statistical procedures, including four scoring methods and four data treatments, to score software-coded emotion expression data. These scoring procedures are illustrated to inform analysis decisions pertaining to the scoring and data treatment of other emotion expression questions and under different experimental circumstances. Overall, we found applying loess smoothing and controlling for baseline facial emotion expression and facial plasticity are recommended methods of data treatment. When scoring facial emotion expression ability, maximum score is preferred. Finally, we discuss the scoring methods and data treatments in the larger context of emotion expression research.

Influence of tumor microenvironment on prognosis in colorectal cancer: Tissue architecture-dependent signature of endosialin (TEM-1) and associated proteins

PubMed Central

O'Shannessy, Daniel J.; Somers, Elizabeth B.; Chandrasekaran, Lakshmi K.; Nicolaides, Nicholas C.; Bordeaux, Jennifer; Gustavson, Mark D.

2014-01-01

Tumor survival is influenced by interactions between tumor cells and the stromal microenvironment. One example is Endosialin (Tumor Endothelial Marker-1 (TEM-1) or CD248), which is expressed primarily by cells of mesenchymal origin and some tumor cells. The expression, as a function of architectural masking, of TEM-1 and its pathway-associated proteins was quantified and examined for association with five-year disease-specific survival on a colorectal cancer (CRC) cohort divided into training (n=330) and validation (n=164) sets. Although stromal expression of TEM-1 had prognostic value, a more significant prognostic signature was obtained through linear combination of five compartment-specific expression scores (TEM-1 Stroma, TEM-1 Tumor Vessel, HIF2α Stromal Vessel, Collagen IV Tumor, and Fibronectin Stroma). This resulted in a single continuous risk score (TAPPS: TEM-1 Associated Pathway Prognostic Signature) which was significantly associated with decreased survival on both the training set [HR=1.76 (95%CI: 1.44-2.15); p<0.001] and validation set [HR=1.38 (95%CI: 1.02-1.88); p=0.04]. Importantly, since prognosis is a critical clinical question in Stage II patients, the TAPPS score also significantly predicted survival in the Stage II patient (n=126) cohort [HR=1.75 (95%CI: 1.22-2.52); p=0.002] suggesting the potential of using the TAPPS score to assess overall risk in CRC patients, and specifically in Stage II patients. PMID:24980818

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

PubMed

Baquero, Maria T; Lostritto, Karen; Gustavson, Mark D; Bassi, Kimberly A; Appia, Franck; Camp, Robert L; Molinaro, Annette M; Harris, Lyndsay N; Rimm, David L

2011-11-02

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients.

PubMed

Chang, Jenny C; Makris, Andreas; Gutierrez, M Carolina; Hilsenbeck, Susan G; Hackett, James R; Jeong, Jennie; Liu, Mei-Lan; Baker, Joffre; Clark-Langone, Kim; Baehner, Frederick L; Sexton, Krsytal; Mohsin, Syed; Gray, Tara; Alvarez, Laura; Chamness, Gary C; Osborne, C Kent; Shak, Steven

2008-03-01

Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Three 10-microm FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P<0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P=0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.

The 90-day prognostic value of serum cyclophilin A in traumatic brain injury.

PubMed

Jin, Hang-Huang; Mao, Tian-Ming; Bai, Zhi-Qiang; Chen, Yuan; Ji, Hai-Long; Jin, Yong

2018-06-07

Cyclophilin A is involved in many inflammatory diseases and its expression is up-regulated after brain injury. We determined if serum cyclophilin A could be used as a marker for severity and 90-day outcome in patients with traumatic brain injury (TBI). Serum cyclophilin A concentrations were quantified in 105 severe TBI patients and 105 healthy individuals. Its association with Glasgow Coma Scale (GCS) score, 90-day mortality and 90-day poor outcome (Glasgow Outcome Scale score of 1-3) were investigated. Serum cyclophilin A concentrations were significantly higher in TBI patients than in healthy individuals. Cyclophilin A concentrations had a close relation to GCS scores and showed a high discriminatory ability for 90-day mortality and poor outcome according to area under receiver operating characteristic curve (AUC). Its AUC was in the range of GCS scores. Moreover, its combination with GCS scores significantly improved the predictive performance of GCS scores alone. In addition, serum cyclophilin A emerged as an independent predictor for 90-day mortality, overall survival and poor outcome. Increased serum cyclophilin A concentrations could reflect trauma severity and unfavorable outcome after head trauma, substantializing cyclophilin A as a potential biomarker for prognostic prediction of TBI. Copyright © 2018 Elsevier B.V. All rights reserved.

Predicting the Onset of PTSD: An Analysis of Facial Expression of Emotion in Reaction to Aggressive Displays

DTIC Science & Technology

2011-04-01

amnesia and diminished responsiveness to the outside world (Henline). The RAND Corporation, a nonprofit research organization, conducted a study beginning...negative relationship between performance scores and NPY levels in that the less NPY a Soldier produced, the more likely the Soldier dissociated and

Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence

PubMed Central

Migliaccio, Ilenia; Chaubal, Vaishali; Wu, Meng-Fen; Pace, Margaret C.; Hartmaier, Ryan; Jiang, Shiming; Edwards, Dean P.; Gutiérrez, M. Carolina; Hilsenbeck, Susan G.; Oesterreich, Steffi

2012-01-01

Silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), also known as nuclear corepressor 2 (NCOR2) is a transcriptional corepressor for multiple members of the nuclear receptor superfamily of transcription factors, including estrogen receptor-α (ERα). In the classical model of corepressor action, SMRT binds to antiestrogen-bound ERα at target promoters and represses ERα transcriptional activity and gene expression. Herein SMRT mRNA and protein expression was examined in a panel of 30 breast cancer cell lines. Expression of both parameters was found to vary considerably amongst lines and the correlation between protein and mRNA expression was very poor (R2 = 0.0775). Therefore, SMRT protein levels were examined by immunohistochemical staining of a tissue microarray of 866 patients with stage I–II breast cancer. Nuclear and cytoplasmic SMRT were scored separately according to the Allred score. The majority of tumors (67 %) were negative for cytoplasmic SMRT, which when detected was found at very low levels. In contrast, nuclear SMRT was broadly detected. There was no significant difference in time to recurrence (TTR) according to SMRT expression levels in the ERα-positive tamoxifen-treated patients (P = 0.297) but the difference was significant in the untreated patients (P = 0.01). In multivariate analysis, ERα-positive tamoxifen-untreated patients with high nuclear SMRT expression (SMRT 5-8, i.e., 2nd to 4th quartile) had a shorter TTR (HR = 1.94, 95 % CI, 1.24–3.04; P = 0.004) while there was no association with SMRT expression for ERα-positive tamoxifen-treated patients. There was no association between SMRT expression and overall survival for patients, regardless of whether they received tamoxifen. Thus while SMRT protein expression was not predictive of outcome after antiestrogen therapy, it may have value in predicting tumor recurrence in patients not receiving adjuvant tamoxifen therapy. PMID:23015261

PRESCHOOL SPEECH ARTICULATION AND NONWORD REPETITION ABILITIES MAY HELP PREDICT EVENTUAL RECOVERY OR PERSISTENCE OF STUTTERING

PubMed Central

Spencer, Caroline; Weber-Fox, Christine

2014-01-01

Purpose In preschool children, we investigated whether expressive and receptive language, phonological, articulatory, and/or verbal working memory proficiencies aid in predicting eventual recovery or persistence of stuttering. Methods Participants included 65 children, including 25 children who do not stutter (CWNS) and 40 who stutter (CWS) recruited at age 3;9–5;8. At initial testing, participants were administered the Test of Auditory Comprehension of Language, 3rd edition (TACL-3), Structured Photographic Expressive Language Test, 3rd edition (SPELT-3), Bankson-Bernthal Test of Phonology-Consonant Inventory subtest (BBTOP-CI), Nonword Repetition Test (NRT; Dollaghan & Campbell, 1998), and Test of Auditory Perceptual Skills-Revised (TAPS-R) auditory number memory and auditory word memory subtests. Stuttering behaviors of CWS were assessed in subsequent years, forming groups whose stuttering eventually persisted (CWS-Per; n=19) or recovered (CWS-Rec; n=21). Proficiency scores in morphosyntactic skills, consonant production, verbal working memory for known words, and phonological working memory and speech production for novel nonwords obtained at the initial testing were analyzed for each group. Results CWS-Per were less proficient than CWNS and CWS-Rec in measures of consonant production (BBTOP-CI) and repetition of novel phonological sequences (NRT). In contrast, receptive language, expressive language, and verbal working memory abilities did not distinguish CWS-Rec from CWS-Per. Binary logistic regression analysis indicated that preschool BBTOP-CI scores and overall NRT proficiency significantly predicted future recovery status. Conclusion Results suggest that phonological and speech articulation abilities in the preschool years should be considered with other predictive factors as part of a comprehensive risk assessment for the development of chronic stuttering. PMID:25173455

The Discovery of Novel Biomarkers Improves Breast Cancer Intrinsic Subtype Prediction and Reconciles the Labels in the METABRIC Data Set

PubMed Central

Milioli, Heloisa Helena; Vimieiro, Renato; Riveros, Carlos; Tishchenko, Inna; Berretta, Regina; Moscato, Pablo

2015-01-01

Background The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, and therapy response. The PAM50 method, based on the expression levels of 50 genes, uses a single sample predictor model to assign subtype labels to samples. Intrinsic errors reported within this assay demonstrate the challenge of identifying and understanding the breast cancer groups. In this study, we aim to: a) identify novel biomarkers for subtype individuation by exploring the competence of a newly proposed method named CM1 score, and b) apply an ensemble learning, as opposed to the use of a single classifier, for sample subtype assignment. The overarching objective is to improve class prediction. Methods and Findings The microarray transcriptome data sets used in this study are: the METABRIC breast cancer data recorded for over 2000 patients, and the public integrated source from ROCK database with 1570 samples. We first computed the CM1 score to identify the probes with highly discriminative patterns of expression across samples of each intrinsic subtype. We further assessed the ability of 42 selected probes on assigning correct subtype labels using 24 different classifiers from the Weka software suite. For comparison, the same method was applied on the list of 50 genes from the PAM50 method. Conclusions The CM1 score portrayed 30 novel biomarkers for predicting breast cancer subtypes, with the confirmation of the role of 12 well-established genes. Intrinsic subtypes assigned using the CM1 list and the ensemble of classifiers are more consistent and homogeneous than the original PAM50 labels. The new subtypes show accurate distributions of current clinical markers ER, PR and HER2, and survival curves in the METABRIC and ROCK data sets. Remarkably, the paradoxical attribution of the original labels reinforces the limitations of employing a single sample classifiers to predict breast cancer intrinsic subtypes. PMID:26132585

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

PubMed

Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

2013-01-01

We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

[Correlation of Rab coupling protein expression with clinicopathological characteristics and prognosis in laryngeal squamous cell carcinoma].

PubMed

Dai, Yaozhang; Liu, Yong; Tian, Xiufen; Zhang, Xin

2015-02-01

To explore the RCP protein expression and its clinicopathological significance in laryngeal squamous cell carcinoma (LSCC). RCP protein expression in human head and neck squamous cell carcinoma cell lines (NP-69, Tu686, Tu212, M2 and M4) was analyzed by Western blotting. Besides, its expression in 87 cases of LSCC, 18 cases of adjacent epithelial mucosa and 16 cases of vocal cord leukoplakia was detected by immunohistochemistry, and their correlation with clinicopathological parameters and patients' outcome was analyzed. The NP-69, Tu212 Tu686, M2 and M4 cells showed a gradual increase in the expression of RCP protein. The average relative expression levels of RCP protein in the NP-69, Tu212, Tu686, M2 and M4 cells were 0.05±0.01, 0.38±0.05, 0.63±0.02, 0.84±0.06 and 0.96±0.04, respectively. The same situation occurred in the adjacent mucosa, vocal cord leukoplakia and LSCC. Specifically, only 3 of 18 adjacent mucosa showed a low RCP expression (scored 0-2). Although the 16 cases of vocal cord leukoplakia had a low RCP expression, all their scores ranged from 0 to 3. While in the LSCC specimens, 59 (67.8%) cases demonstrated a high RCP expression (scored 8-15), 18 cases showed a lower RCP expression (scored 4-7), and only 10 cases were scored 2-3. Among the 87 LSCC cases, there were 28 cases (32.2%) of low RCP expression and 59 cases of high RCP expression. All the 18 cases of cancer-adjacent tissues and 16 cases of vocal cord leukoplakia were of low RCP expression. RCP overexpression was significantly associated with T classification, clinical staging, lymph node metastasis and recurrence (P<0.05 for all). Survival analysis revealed that the 5-year survival rate was 40.0% in the patients with high RCP expression and 75.0% in the patients with low RCP expression, the tumor-free 5-year survival rate was 30.7% and 64.0%, respectively, both showing a significant difference between the two subgroups (P<0.05). Univariate analysis revealed that alcohol history; smoking, T classification, clinical staging, lymph node metastasis and RCP expression were significantly associated with a poor prognosis (P<0.05 for all). The multivariate analysis showed that only recurrence and RCP expression were independent prognostic factors affecting the prognosis for patients with LSCC (P<0.05 for both). Expression of RCP protein may contribute to the malignant progression of LSCC, and may become a novel marker predicting tumor recurrence, cervical lymph node metastasis and prognosis for patients with laryngeal squamous cell carcinoma.

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

PubMed

Eminaga, Okyaz; Wei, Wei; Hawley, Sarah J; Auman, Heidi; Newcomb, Lisa F; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin E; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; McKenney, Jesse K; Feng, Ziding; Fazli, Ladan; Brooks, James D

2016-01-01

The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters. MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test. The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03-1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS). In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

PubMed

van Kessel, Kim E M; van de Werken, Harmen J G; Lurkin, Irene; Ziel-van der Made, Angelique C J; Zwarthoff, Ellen C; Boormans, Joost L

2017-01-01

Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy. We studied diagnostic transurethral resection of bladder tumors (dTURBT) of 150 MIBC patients (urothelial carcinoma) who were subsequently treated by radical cystectomy and pelvic lymph node dissection. RNA was isolated and the expression level of the 20 genes was determined on a qRT-PCR platform. Normalized Ct values were used to calculate a risk score to predict the presence of node-positive disease. The Cancer Genome Atlas (TCGA) RNA expression data was analyzed to subsequently validate the results. In a univariate regression analysis, none of the 20 genes significantly correlated with node-positive disease. The area under the curve of the risk score calculated by the 20-gene expression signature was 0.54 (95% Confidence Interval: 0.44-0.65) versus 0.67 for the model published by Smith et al. Node-negative patients had a significantly lower tumor grade at TURBT (p = 0.03), a lower pT stage (p<0.01) and less frequent lymphovascular invasion (13% versus 38%, p<0.01) at radical cystectomy than node-positive patients. In addition, in the TCGA data, none of the 20 genes was differentially expressed in node-negative versus node-positive patients. We conclude that a 20-gene expression signature developed for nodal staging of MIBC at radical cystectomy could not be validated on a qRT-PCR platform in a large cohort of dTURBT specimens.

Evaluation of pre-implantation kidney biopsies: comparison of Banff criteria to a morphometric approach.

PubMed

Lopes, José António; Moreso, Francesc; Riera, Luis; Carrera, Marta; Ibernon, Meritxell; Fulladosa, Xavier; Grinyó, Josep Maria; Serón, Daniel

2005-04-01

Donor glomerulosclerosis, interstitial fibrosis, and fibrous intimal thickening correlate with graft outcome. We evaluate chronic lesions in donor biopsies according to Banff criteria and with a morphometric technique to ascertain their predictive value on graft outcome. We evaluated 77 cadaveric donor biopsies according to Banff criteria. Glomerulosclerosis was expressed as the percentage of global sclerotic glomeruli. The following morphometric parameters were obtained: cortical interstitial volume fraction (Vvint/c), cortical glomerular volume fraction (Vvglom/c), mean glomerular volume (Vg), mean and maximal intimal arterial volume fraction (Vvintima/art), and Vvintima/art of the largest artery. We evaluated the correlation of histologic lesions with delayed graft function, 3 months' glomerular filtration rate (GFR), and death-censored graft survival. Multivariate logistic regression showed that delayed graft function was associated with cv score [relative risk (RR) 4.2 and 95% CI 1.1 to 16.0) and glomerulosclerosis (RR 1.06 and 95% CI 1.01 to 1.13). Stepwise regression showed that Vvint/c and glomerulosclerosis were independent predictors of 3 months' GFR (R= 0.62, P= 0.0001). Repeated analysis not considering morphometric parameters showed that glomerulosclerosis, cv score and ci score were independent predictors of 3 months' GFR (R= 0.64, P= 0.0001). A donor chronic damage score was generated considering glomerulosclerosis, cv score and ci score. This score after adjusting for clinical variables was associated with 3 months' GFR (R= 0.71, P < 0.0001) and death-censored graft survival (RR 2.2 and 95% CI 1.3 to 3.7). Combined evaluation of donor glomerulosclerosis, chronic vascular and interstitial damage according to Banff criteria allows a precise prediction of graft outcome. Morphometric evaluation of donor biopsies does not improve the predictive value of semiquantitative grading.

Spoken Language Development in Children Following Cochlear Implantation

PubMed Central

Niparko, John K.; Tobey, Emily A.; Thal, Donna J.; Eisenberg, Laurie S.; Wang, Nae-Yuh; Quittner, Alexandra L.; Fink, Nancy E.

2010-01-01

Context Cochlear implantation (CI) is a surgical alternative to traditional amplification (hearing aids) that can facilitate spoken language development in young children with severe-to-profound sensorineural hearing loss (SNHL). Objective To prospectively assess spoken language acquisition following CI in young children with adjustment of co-variates. Design, Setting, and Participants Prospective, longitudinal, and multidimensional assessment of spoken language growth over a 3-year period following CI. Prospective cohort study of children who underwent CI before 5 years of age (n=188) from 6 US centers and hearing children of similar ages (n=97) from 2 preschools recruited between November, 2002 and December, 2004. Follow-up completed between November, 2005 and May, 2008. Main Outcome Measures Performance on measures of spoken language comprehension and expression. Results Children undergoing CI showed greater growth in spoken language performance (10.4;[95% confidence interval: 9.6–11.2] points/year in comprehension; 8.4;[7.8–9.0] in expression) than would be predicted by their pre-CI baseline scores (5.4;[4.1–6.7] comprehension; 5.8;[4.6–7.0] expression). Although mean scores were not restored to age-appropriate levels after 3 years, significantly greater annual rates of language acquisition were observed in children who were younger at CI (1.1;[0.5–1.7] points in comprehension per year younger; 1.0;[0.6–1.5] in expression), and in children with shorter histories of hearing deficit (0.8;[0.2,1.2] points in comprehension per year shorter; 0.6;[0.2–1.0] for expression). In multivariable analyses, greater residual hearing prior to CI, higher ratings of parent-child interactions, and higher SES associated with greater rates of growth in comprehension and expression. Conclusions The use of cochlear implants in young children was associated with better spoken language learning than would be predicted from their pre-implantation scores. However, discrepancies between participants’ chronologic and language age persisted after CI, underscoring the importance of early CI in appropriately selected candidates. PMID:20407059

The effect of differential listening experience on the development of expressive and receptive language in children with bilateral cochlear implants.

PubMed

Hess, Christi; Zettler-Greeley, Cynthia; Godar, Shelly P; Ellis-Weismer, Susan; Litovsky, Ruth Y

2014-01-01

Growing evidence suggests that children who are deaf and use cochlear implants (CIs) can communicate effectively using spoken language. Research has reported that age of implantation and length of experience with the CI play an important role in a predicting a child's linguistic development. In recent years, the increase in the number of children receiving bilateral CIs (BiCIs) has led to interest in new variables that may also influence the development of hearing, speech, and language abilities, such as length of bilateral listening experience and the length of time between the implantation of the two CIs. One goal of the present study was to determine how a cohort of children with BiCIs performed on standardized measures of language and nonverbal cognition. This study examined the relationship between performance on language and nonverbal intelligence quotient (IQ) tests and the ages at implantation of the first CI and second CI. This study also examined whether early bilateral activation is related to better language scores. Children with BiCIs (n = 39; ages 4 to 9 years) were tested on two standardized measures, the Test of Language Development and the Leiter International Performance Scale-Revised, to evaluate their expressive/receptive language skills and nonverbal IQ/memory. Hierarchical regression analyses were used to evaluate whether BiCI hearing experience predicts language performance. While large intersubject variability existed, on average, almost all the children with BiCIs scored within or above normal limits on measures of nonverbal cognition. Expressive and receptive language scores were highly variable, less likely to be above the normative mean, and did not correlate with Length of first CI Use, defined as length of auditory experience with one cochlear implant, or Length of second CI Use, defined as length of auditory experience with two cochlear implants. All children in the present study had BiCIs. Most IQ scores were either at or above that found in the general population of typically hearing children. However, there was greater variability in their performance on a standardized test of expressive and receptive language. This cohort of children, who are mainstreamed in schools at age-appropriate grades, whose mothers' education is high, and whose families' socioecononomic status is high, had, as a group, on average, language scores within the same range as the normative sample of hearing children. Further research identifying the predictors that contribute to the high variability in both expressive and receptive language scores in children with BiCIs will provide useful information that can aid in clinical management and decision making.

Identification of a 5‑lncRNA signature‑based risk scoring system for survival prediction in colorectal cancer.

PubMed

Gu, Liqiang; Yu, Jun; Wang, Qing; Xu, Bin; Ji, Liechen; Yu, Lin; Zhang, Xipeng; Cai, Hui

2018-05-03

The present study aimed to investigate potential prognostic long noncoding RNAs (lncRNAs) associated with colorectal cancer (CRC). An mRNA‑seq dataset obtained from The Cancer Genome Atlas was employed to identify the differentially expressed lncRNAs (DELs) between CRC patients with good and poor prognoses. Subsequently, univariate and multivariate Cox regression analyses were conducted to analyze the prognosis‑associated lncRNAs among all DELs. In addition, a risk scoring system was developed according to the expression levels of the prognostic lncRNAs, which was then applied to a training set and an independent testing set. Furthermore, the co‑expressed genes of prognostic lncRNAs were screened using a Multi‑Experiment Matrix online tool for construction of lncRNA‑gene networks. Finally, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology (GO) function enrichment analyses were performed on genes in the lncRNA‑gene networks using KOBAS, GOATOOLS and ClusterProfiler. The present study identified 82 DELs, of which long intergenic nonprotein coding RNA 2159, RP11‑452L6.6, RP11‑894P9.1 and RP11‑69M1.6, and whey acidic protein four‑disulfide core domain 21 (WFDC21P) were reported to be independently associated with the prognosis of patients with CRC. A 5‑lncRNA signature‑based risk scoring system was developed, which may be used to classify patients into low‑ and high‑risk groups with significantly different recurrence‑free survival times in the training and testing sets (P<0.05). Co‑expressed genes of WFDC21P or RP11‑69M1.6 were utilized to construct the lncRNA‑gene networks. Genes in the networks were significantly enriched in 'tight junction', 'focal adhesion' and 'regulation of actin cytoskeleton' pathways, and numerous GO terms associated with 'reactive oxygen species metabolism' and 'nitric oxide metabolism'. The present study proposed a 5‑lncRNA signature‑based risk scoring system for predicting the prognosis of patients with CRC, and revealed the associated signaling pathways and biological processes. The results of the present study may help improve prognostic evaluation in clinical practice.

Verbal short-term memory development and spoken language outcomes in deaf children with cochlear implants.

PubMed

Harris, Michael S; Kronenberger, William G; Gao, Sujuan; Hoen, Helena M; Miyamoto, Richard T; Pisoni, David B

2013-01-01

Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children. Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF). Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables. Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.

DiRE: identifying distant regulatory elements of co-expressed genes

PubMed Central

Gotea, Valer; Ovcharenko, Ivan

2008-01-01

Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, comparative genomics and profiles of transcription factor binding sites (TFBSs) to determine TFBS-association signatures that can be used for discriminating specific regulatory functions. DiRE's unique feature is its ability to detect REs outside of proximal promoter regions, as it takes advantage of the full gene locus to conduct the search. DiRE can predict common REs for any set of input genes for which the user has prior knowledge of co-expression, co-function or other biologically meaningful grouping. The server predicts function-specific REs consisting of clusters of specifically-associated TFBSs and it also scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes. Its integration with the Array2BIO server allows users to start their analysis with raw microarray expression data. The DiRE web server is freely available at http://dire.dcode.org. PMID:18487623

Association of predeployment gaze bias for emotion stimuli with later symptoms of PTSD and depression in soldiers deployed in Iraq.

PubMed

Beevers, Christopher G; Lee, Han-Joo; Wells, Tony T; Ellis, Alissa J; Telch, Michael J

2011-07-01

Biased processing of emotion stimuli is thought to confer vulnerability to psychopathology, but few longitudinal studies of this link have been conducted. The authors examined the relationship between predeployment gaze bias for emotion stimuli and later symptoms of posttraumatic stress disorder (PTSD) and depression in soldiers deployed to Iraq. An eye-tracking paradigm was used to assess line of gaze in 139 soldiers while they viewed a two-by-two matrix of fearful, sad, happy, and neutral facial expressions before they were deployed to Iraq. Once they were deployed, the soldiers periodically reported on their levels of war zone stress exposure and symptoms of PTSD and depression. War zone stress exposure predicted higher scores on PTSD and depression symptom measures; however, eye gaze bias moderated this relationship. In soldiers with war zone stress exposure, shorter mean fixation time when viewing fearful faces predicted higher PTSD symptom scores, and greater total fixation time and longer mean fixation time for sad faces predicted higher depressive symptom scores. Biased processing of emotion stimuli, as measured by gaze bias, appears to confer vulnerability to symptoms of PTSD and depression in soldiers who experience war zone stress.

A VEGF-dependent gene signature enriched in mesenchymal ovarian cancer predicts patient prognosis.

PubMed

Yin, Xia; Wang, Xiaojie; Shen, Boqiang; Jing, Ying; Li, Qing; Cai, Mei-Chun; Gu, Zhuowei; Yang, Qi; Zhang, Zhenfeng; Liu, Jin; Li, Hongxia; Di, Wen; Zhuang, Guanglei

2016-08-08

We have previously reported surrogate biomarkers of VEGF pathway activities with the potential to provide predictive information for anti-VEGF therapies. The aim of this study was to systematically evaluate a new VEGF-dependent gene signature (VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis. Using microarray profiling and cross-species analysis, we identified 140-gene mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of vasculature and basement membrane genes. In patients who received bevacizumab therapy and showed partial response, the expressions of VDGs (summarized to yield VDGs scores) were markedly decreased in post-treatment biopsies compared with pre-treatment baselines. In contrast, VDGs scores were not significantly altered following bevacizumab treatment in patients with stable or progressive disease. Analysis of VDGs in ovarian cancer showed that VDGs as a prognostic signature was able to predict patient outcome. Correlation estimation of VDGs scores and molecular features revealed that VDGs was overrepresented in mesenchymal subtype and BRCA mutation carriers. These findings highlighted the prognostic role of VEGF-mediated angiogenesis in ovarian cancer, and proposed a VEGF-dependent gene signature as a molecular basis for developing novel diagnostic strategies to aid patient selection for VEGF-targeted agents.

A Computer-Assisted Instruction Phonological Sensitivity Program for Preschool Children At-Risk for Reading Problems.

ERIC Educational Resources Information Center

Lonigan, Christopher J.; Driscoll, Kimberly; Phillips, Beth M.; Cantor, Brenlee G.; Anthony, Jason L.; Goldstein, Howard

2003-01-01

A study evaluated the use of computer-assisted instruction (CAI) to provide training in phonological sensitivity skills to 45 preschool children at-risk for reading problems. Children exposed to CAI made significantly greater gains on rhyming and elision skills compared to controls. Expressive vocabulary scores were predictive of pre- to posttest…

Tumor Cell-Free DNA Copy Number Instability Predicts Therapeutic Response to Immunotherapy.

PubMed

Weiss, Glen J; Beck, Julia; Braun, Donald P; Bornemann-Kolatzki, Kristen; Barilla, Heather; Cubello, Rhiannon; Quan, Walter; Sangal, Ashish; Khemka, Vivek; Waypa, Jordan; Mitchell, William M; Urnovitz, Howard; Schütz, Ekkehard

2017-09-01

Purpose: Chromosomal instability is a fundamental property of cancer, which can be quantified by next-generation sequencing (NGS) from plasma/serum-derived cell-free DNA (cfDNA). We hypothesized that cfDNA could be used as a real-time surrogate for imaging analysis of disease status as a function of response to immunotherapy and as a more reliable tool than tumor biomarkers. Experimental Design: Plasma cfDNA sequences from 56 patients with diverse advanced cancers were prospectively collected and analyzed in a single-blind study for copy number variations, expressed as a quantitative chromosomal number instability (CNI) score versus 126 noncancer controls in a training set of 23 and a blinded validation set of 33. Tumor biomarker concentrations and a surrogate marker for T regulatory cells (Tregs) were comparatively analyzed. Results: Elevated CNI scores were observed in 51 of 56 patients prior to therapy. The blinded validation cohort provided an overall prediction accuracy of 83% (25/30) and a positive predictive value of CNI score for progression of 92% (11/12). The combination of CNI score before cycle (Cy) 2 and 3 yielded a correct prediction for progression in all 13 patients. The CNI score also correctly identified cases of pseudo-tumor progression from hyperprogression. Before Cy2 and Cy3, there was no significant correlation for protein tumor markers, total cfDNA, or surrogate Tregs. Conclusions: Chromosomal instability quantification in plasma cfDNA can serve as an early indicator of response to immunotherapy. The method has the potential to reduce health care costs and disease burden for cancer patients following further validation. Clin Cancer Res; 23(17); 5074-81. ©2017 AACR . ©2017 American Association for Cancer Research.

Pooling score: an endoscopic model for evaluating severity of dysphagia

PubMed Central

Farneti, D

2008-01-01

Summary The finding of secretions and bolus pooling is of great diagnostic interest in the evaluation of subjects with swallowing disorders. Bedside evaluation alone, in subjects at risk for aspiration, can underestimate this parameter. The usefulness of endoscopic investigation for the evaluation of subjects with swallowing disorders is stressed, in order to plan treatment and follow-up. Based on endoscopic evaluation of material pooling we devised a score expressing the severity of dysphagia. This value takes into account endoscopic landmarks and other parameters of bedside evaluation. Endoscopic and bedside data were collected from a heterogeneous population of 520 consecutive patients seen in our Service over a 6-year period. By means of the test of equality of group means and logistic regression, parameters able to significantly predict aspiration in the series were identified. An ordinal number was attributed to each parameter in order to obtain scores expressing three degrees of severity of dysphagia: mild, moderate, severe. The scores can be used to guide the management of patients in a simple way, providing indications for targeted referral to the speech pathologist and for tracking the disorder over time. This investigation represents the basis for future research aimed at validating the scores in a larger case series. PMID:18646575

Performance of Polygenic Scores for Predicting Phobic Anxiety

PubMed Central

Walter, Stefan; Glymour, M. Maria; Koenen, Karestan; Liang, Liming; Tchetgen Tchetgen, Eric J.; Cornelis, Marilyn; Chang, Shun-Chiao; Rimm, Eric; Kawachi, Ichiro; Kubzansky, Laura D.

2013-01-01

Context Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. Objective To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Design Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Setting and Participants Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Main Outcome Measure Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. Results We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. Conclusion There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20–40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety. PMID:24278274

Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake.

PubMed

Karatayev, Olga; Barson, Jessica R; Carr, Ambrose J; Baylan, Jessica; Chen, Yu-Wei; Leibowitz, Sarah F

2010-06-01

To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity. 2010 Elsevier Inc. All rights reserved.

Examining Maternal Psychopathology, Family Functioning and Coping Skills in Childhood Obesity: A Case-Control Study.

PubMed

Blanco, Miriam; Sepulveda, Ana R; Lacruz, Tatiana; Parks, Melissa; Real, Beatriz; Martin-Peinador, Yolanda; Román, Francisco J

2017-09-01

The shared family environment is an important risk factor in the development of childhood obesity. This study aims to examine differences in maternal psychopathology, family functioning, expressed emotion and coping skills between families of a child with obesity and those with a normal-weight child. This case-control study consisted of 50 mothers with a child (age 8-12 years) with obesity (p ≥ 97) and a control group of 50 mothers of a child with normal weight (p < 85), matched for age, sex and socio-economic status. Compared with families with normal-weight children, those with children with obesity showed significant differences in levels of trait anxiety, criticism and over-protectiveness, and maladaptive coping skills. Structural equation modelling revealed that the mothers' psychopathology predicted children's body mass index (BMI) z-scores through expressed emotion and maladaptive coping scores. There were significant direct and indirect relations among maternal BMI, psychopathology, expressed emotion and coping, which all together explained 26.5% of variance of children's BMI z-scores. Considering this relation between maternal variables and child weight status, childhood obesity intervention programs may benefit from targeting maternal BMI, psychopathology, expressed emotion and coping skills. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Does the ability to express different emotions predict different indices of physical health? A skill-based study of physical symptoms and heart rate variability.

PubMed

Tuck, Natalie L; Adams, Kathryn S; Consedine, Nathan S

2017-09-01

The outward expression of emotion has been frequently associated with better health outcomes, whereas suppressing emotion is thought to contribute to worse physical health. However, work has typically focused on trait expressive tendencies and the possibility that individual differences in the ability to express specific emotions may also be associated with health has not been widely tested. A cross-sectional study of community dwelling adults. One hundred and twenty-eight participants aged 18-88 years completed questionnaires assessing demographics and health status, before attending a testing session in which resting heart rate variability (HRV) was assessed. Participants then completed a performance-based test of expressive regulatory skill in which they were instructed to enhance and suppress their emotional expressions while they watched film clips validated to elicit amusement, sadness, and anger. Participants rated subjective emotional experience before and after each clip, and their degree of expressivity was scored using FACS-based Noldus FaceReader. Missing data resulted in a final sample size of 117. Linear regressions controlling for age, sex, diagnoses, and trait emotion revealed that greater ability to enhance sad expressions was associated with higher HRV while the ability to enhance expressions of joy was associated with lower symptom interference. In parallel models, the ability to flexibly regulate (both enhance and suppress) expressions of joy and sadness was also associated with lower symptom interference. Findings suggest that the ability to regulate expressions of both sadness and joy is associated with health indices even when controlling for trait affect and potential confounds. The present findings offer early evidence that individual differences in the ability to regulate the outward expression of emotion may be relevant to health and suggest that expressive regulatory skills offer a novel avenue for research and intervention. Statement of contribution What is already known on this subject The tendency to outwardly express felt emotion generally predicts better health, whereas expressive suppression typically predicts worse health outcomes. Most work has been based on trait assessments; however, the ability to regulate the expression of felt emotion can be objectively assessed using performance-based tests. Prior work in mental health suggests that the ability to flexibly up- and downregulate the expression of emotion predicts better outcomes. What does this study add The first evidence that the ability to flexibly regulate expressions predicts indices of health. Skill in both expressing and suppressing facial expressions predicts better reported health. Skills with different emotions differentially predict symptom interference and cardiac vagal tone. © 2017 The British Psychological Society.

Comparative prognostic value of epidermal growth factor quantitative protein expression compared with FISH for head and neck squamous cell carcinoma.

PubMed

Pectasides, Eirini; Rampias, Theodore; Kountourakis, Panteleimon; Sasaki, Clarence; Kowalski, Diane; Fountzilas, George; Zaramboukas, Thomas; Rimm, David; Burtness, Barbara; Psyrri, Amanda

2011-05-01

Epidermal growth factor receptor (EGFR) overexpression correlates with recurrence and with treatment resistance in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the relationship of EGFR gene copy number utilizing FISH and protein expression with automated quantitative analysis (AQUA) and to correlate those with patient outcome. A tissue microarray composed of 102 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis; Abbott Laboratories) and EGFR protein expression using AQUA analysis of EGFR staining scored on a scale of 0 to 255. We evaluated associations of EGFR FISH status and AQUA score with clinicopathologic parameters and survival prognosis. Eleven (17.2%) of 64 tumors with FISH results showed EGFR high polysomy and/or gene amplification (FISH positive). Protein levels assessed by AQUA in FISH-positive cases were significantly higher (P = 0.04) than in FISH-negative cases. Using the continuous AQUA scores for EGFR expression, AQUA and FISH showed significant agreement (Pearson's ρ = 0.353, P = 0.04). Patients with high tumor EGFR protein expression had inferior 5-year overall survival (27.7%) compared with those with low tumor EGFR expression (54%; P = 0.029). There was no significant association between EGFR FISH status and overall survival (P = 0.201). In the multivariate model, high tumor EGFR protein expression status remained an independent prognostic factor for overall survival (P = 0.047). EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. EGFR protein levels assessed by AQUA strongly predict for patient outcome in HNSCC, whereas EGFR FISH status does not provide prognostic information. ©2011 AACR.

Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients.

PubMed

Rosenberg, Steven; Elashoff, Michael R; Beineke, Philip; Daniels, Susan E; Wingrove, James A; Tingley, Whittemore G; Sager, Philip T; Sehnert, Amy J; Yau, May; Kraus, William E; Newby, L Kristin; Schwartz, Robert S; Voros, Szilard; Ellis, Stephen G; Tahirkheli, Naeem; Waksman, Ron; McPherson, John; Lansky, Alexandra; Winn, Mary E; Schork, Nicholas J; Topol, Eric J

2010-10-05

Diagnosing obstructive coronary artery disease (CAD) in at-risk patients can be challenging and typically requires both noninvasive imaging methods and coronary angiography, the gold standard. Previous studies have suggested that peripheral blood gene expression can indicate the presence of CAD. To validate a previously developed 23-gene, expression-based classification test for diagnosis of obstructive CAD in nondiabetic patients. Multicenter prospective trial with blood samples obtained before coronary angiography. (ClinicalTrials.gov registration number: NCT00500617) SETTING: 39 centers in the United States. An independent validation cohort of 526 nondiabetic patients with a clinical indication for coronary angiography. Receiver-operating characteristic (ROC) analysis of classifier score measured by real-time polymerase chain reaction, additivity to clinical factors, and reclassification of patient disease likelihood versus disease status defined by quantitative coronary angiography. Obstructive CAD was defined as 50% or greater stenosis in 1 or more major coronary arteries by quantitative coronary angiography. The area under the ROC curve (AUC) was 0.70 ± 0.02 (P < 0.001); the test added to clinical variables (Diamond-Forrester method) (AUC, 0.72 with the test vs. 0.66 without; P = 0.003) and added somewhat to an expanded clinical model (AUC, 0.745 with the test vs. 0.732 without; P = 0.089). The test improved net reclassification over both the Diamond-Forrester method and the expanded clinical model (P < 0.001). At a score threshold that corresponded to a 20% likelihood of obstructive CAD (14.75), the sensitivity and specificity were 85% and 43% (yielding a negative predictive value of 83% and a positive predictive value of 46%), with 33% of patient scores below this threshold. Patients with chronic inflammatory disorders, elevated levels of leukocytes or cardiac protein markers, or diabetes were excluded. A noninvasive whole-blood test based on gene expression and demographic characteristics may be useful for assessing obstructive CAD in nondiabetic patients without known CAD. CardioDx.

Concurrent validity of the Wheeler signs of homosexuality in the Rorschach: P (Ci/Rj).

PubMed

Stone, N M; Schneider, R E

1975-12-01

The Rorschach protocols of 43 males consecutively admitted to a university outpatient clinic were scored for frequency of the 20 Wheeler signs of homosexuality. Based on case history data, patients were assigned to homosexual, sex-role disturbed, or normal-control groups. In addition to the traditional group comparison the results were analyzed to yield P (Ci/Rj); that is, the probability of criterion group membership given test indicator. Both the homosexual and sex-role disturbed group displayed significantly more Wheeler signs than normals. Furthermore, given a Wheeler sign score of 15%, .75 of the predicted-homosexual group would be correctly classified compared to a .21 baserate prediction. It was suggested that expressing results as P (Ci/Rj) provides information more relevant to the clinician than is provided by the traditional practice of reporting significant differences between groups.

Limited improvement of incorporating primary circulating prostate cells with the CAPRA score to predict biochemical failure-free outcome of radical prostatectomy for prostate cancer.

PubMed

Murray, Nigel P; Aedo, Socrates; Fuentealba, Cynthia; Jacob, Omar; Reyes, Eduardo; Novoa, Camilo; Orellana, Sebastian; Orellana, Nelson

2016-10-01

To establish a prediction model for early biochemical failure based on the Cancer of the Prostate Risk Assessment (CAPRA) score, the presence or absence of primary circulating prostate cells (CPC) and the number of primary CPC (nCPC)/8ml blood sample is detected before surgery. A prospective single-center study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinical-pathological findings were used to calculate the CAPRA score. Before surgery blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen and P504S, and the presence or absence of CPCs and the number of cells detected/8ml blood sample was registered. Patients were followed up for up to 5 years; biochemical failure was defined as a prostate-specific antigen>0.2ng/ml. The validity of the CAPRA score was calibrated using partial validation, and the fractional polynomial Cox proportional hazard regression was used to build 3 models, which underwent a decision analysis curve to determine the predictive value of the 3 models with respect to biochemical failure. A total of 267 men participated, mean age 65.80 years, and after 5 years of follow-up the biochemical-free survival was 67.42%. The model using CAPRA score showed a hazards ratio (HR) of 5.76 between low and high-risk groups, that of CPC with a HR of 26.84 between positive and negative groups, and the combined model showed a HR of 4.16 for CAPRA score and 19.93 for CPC. Using the continuous variable nCPC, there was no improvement in the predictive value of the model compared with the model using a positive-negative result of CPC detection. The combined CAPRA-nCPC model showed an improvement of the predictive performance for biochemical failure using the Harrell׳s C concordance test and a net benefit on DCA in comparison with either model used separately. The use of primary CPC as a predictive factor based on their presence or absence did not predict aggressive disease or biochemical failure. Although the use of a combined CAPRA-nCPC model improves the prediction of biochemical failure in patients undergoing radical prostatectomy for prostate cancer, this is minimal. The use of the presence or absence of primary CPCs alone did not predict aggressive disease or biochemical failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients.

PubMed

Jennings, C J; Murer, B; O'Grady, A; Hearn, L M; Harvey, B J; Kay, E W; Thomas, W

2015-06-30

Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence. The expression of cyclin-dependent kinase inhibitor p16/INK4A was evaluated by immunohistochemistry using tumour biopsy specimens from 88 MPM cases and a semi-quantitative score for p16/INK4A expression was obtained. Post-diagnosis survival and the survival benefit of chemotherapeutic intervention was correlated with p16/INK4A expression. A low, intermediate and high score for p16/INK4A expression was observed for 45 (51.1%), 28 (31.8%) and 15 (17.1%) of the MPM cases, respectively. Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression (log-rank P<0.001). Those patients with sustained p16/INK4A expression who received chemotherapy also had a better survival than those treated patients whose tumours had lost p16/INK4A expression (log-rank P<0.001). Sustained p16/INK4A expression predicts better post-diagnosis survival in MPM and also better survival following chemotherapeutic intervention.

Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients

PubMed Central

Jennings, C J; Murer, B; O'Grady, A; Hearn, L M; Harvey, B J; Kay, E W; Thomas, W

2015-01-01

Background: Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence. Methods: The expression of cyclin-dependent kinase inhibitor p16/INK4A was evaluated by immunohistochemistry using tumour biopsy specimens from 88 MPM cases and a semi-quantitative score for p16/INK4A expression was obtained. Post-diagnosis survival and the survival benefit of chemotherapeutic intervention was correlated with p16/INK4A expression. Results: A low, intermediate and high score for p16/INK4A expression was observed for 45 (51.1%), 28 (31.8%) and 15 (17.1%) of the MPM cases, respectively. Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression (log-rank P<0.001). Those patients with sustained p16/INK4A expression who received chemotherapy also had a better survival than those treated patients whose tumours had lost p16/INK4A expression (log-rank P<0.001). Conclusions: Sustained p16/INK4A expression predicts better post-diagnosis survival in MPM and also better survival following chemotherapeutic intervention. PMID:26057448

Association between circulating microRNA-208a and severity of coronary heart disease.

PubMed

Zhang, Yao; Li, Hai-Hong; Yang, Rui; Yang, Bai-Jing; Gao, Zhao-Yu

2017-09-01

Circulating microRNA (miR)-208a is specifically expressed in the heart muscle, which is involved in the regulation of myosin during cardiac development. Previous studies reported that cardiac-specific miR-208a level is significantly higher in plasma of coronary heart disease (CHD) patients. However, whether it correlates with severity of CHD, has never been elucidated before. The aim of this study was to explore the association between miR-208a and the presence and severity of CHD. Samples were collected from 290 CHD patients and 110 subjects with angiographic exclusion of CHD. Circulating miRNA-208a expression was detected using quantitative real-time PCR. The Gensini score was used to evaluate the severity of coronary stenotic lesions. Expression of miRNA-208a was identified on the basis of the quartiles of the Gensini score, and association between the miRNA-208a levels and CHD was analyzed. Diagnostic potential of miR-208a of CHD was performed by ROC analysis. CHD patients had higher miRNA-208a expression (1.61, 0.45-3.86 vs. 0.66, 0.11-1.42, p < .001), and the biomarker level significantly increased following an increasing the Gensini score (p < .001). Gensini score was significantly associated with miRNA-208a expression (r = 0.8525, p < .001). The optimal cut-off value of the relative level of miR-208a was with a specificity of 93.6% and a sensitivity of 75.5%. The AUC of miR-208a was 0.919 (95% CI, 0.893-0.945; p < .001). These preliminary results suggest that the expression of miR-208a may be associated with atherogenesis. The level of circulating miR-208a in predicting the severity of coronary atherosclerosis may have a relatively certain value.

A comparison of machine learning techniques for survival prediction in breast cancer

PubMed Central

2011-01-01

Background The ability to accurately classify cancer patients into risk classes, i.e. to predict the outcome of the pathology on an individual basis, is a key ingredient in making therapeutic decisions. In recent years gene expression data have been successfully used to complement the clinical and histological criteria traditionally used in such prediction. Many "gene expression signatures" have been developed, i.e. sets of genes whose expression values in a tumor can be used to predict the outcome of the pathology. Here we investigate the use of several machine learning techniques to classify breast cancer patients using one of such signatures, the well established 70-gene signature. Results We show that Genetic Programming performs significantly better than Support Vector Machines, Multilayered Perceptrons and Random Forests in classifying patients from the NKI breast cancer dataset, and comparably to the scoring-based method originally proposed by the authors of the 70-gene signature. Furthermore, Genetic Programming is able to perform an automatic feature selection. Conclusions Since the performance of Genetic Programming is likely to be improvable compared to the out-of-the-box approach used here, and given the biological insight potentially provided by the Genetic Programming solutions, we conclude that Genetic Programming methods are worth further investigation as a tool for cancer patient classification based on gene expression data. PMID:21569330

GSEH: A Novel Approach to Select Prostate Cancer-Associated Genes Using Gene Expression Heterogeneity.

PubMed

Kim, Hyunjin; Choi, Sang-Min; Park, Sanghyun

2018-01-01

When a gene shows varying levels of expression among normal people but similar levels in disease patients or shows similar levels of expression among normal people but different levels in disease patients, we can assume that the gene is associated with the disease. By utilizing this gene expression heterogeneity, we can obtain additional information that abets discovery of disease-associated genes. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes on the basis of the degree of gene expression heterogeneity to find "differentially predicted" genes. Through the proposed method, we discovered more prostate cancer-associated genes than 10 comparable methods. The genes prioritized by the proposed method are potentially significant to biological processes of a disease and can provide insight into them.

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.

PubMed

Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D

2012-09-13

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

Early Gray-Matter and White-Matter Concentration in Infancy Predict Later Language Skills: A Whole Brain Voxel-Based Morphometry Study

ERIC Educational Resources Information Center

Can, Dilara Deniz; Richards, Todd; Kuhl, Patricia K.

2013-01-01

Magnetic Resonance Imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months.…

Development and Transfer of Vocabulary Knowledge in Spanish-Speaking Language Minority Preschool Children

ERIC Educational Resources Information Center

Goodrich, J. Marc; Lonigan, Christopher J.; Kleuver, Cherie G.; Farver, Joann M.

2016-01-01

In this study we evaluated the predictive validity of conceptual scoring. Two independent samples of Spanish-speaking language minority preschoolers (Sample 1: N = 96, mean age = 54.51 months, 54.3% male; Sample 2: N = 116, mean age = 60·70 months, 56.0% male) completed measures of receptive, expressive, and definitional vocabulary in their first…

Exploring Regulatory Mechanisms of Atrial Myocyte Hypertrophy of Mitral Regurgitation through Gene Expression Profiling Analysis: Role of NFAT in Cardiac Hypertrophy

PubMed Central

Chang, Tzu-Hao; Chen, Mien-Cheng; Chang, Jen-Ping; Huang, Hsien-Da; Ho, Wan-Chun; Lin, Yu-Sheng; Pan, Kuo-Li; Huang, Yao-Kuang; Liu, Wen-Hao; Wu, Chia-Chen

2016-01-01

Background Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. Methods and Results This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that “NFAT in cardiac hypertrophy” pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated) through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1) were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC. Conclusions Differentially expressed genes in the “NFAT in cardiac hypertrophy” pathway may play a critical role in the atrial myocyte hypertrophy of MR patients. PMID:27907007

Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities

PubMed Central

2011-01-01

Background Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element. Results This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called Gene expression and Transcription factor activity based Relevance Network (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to E. coli data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of E. coli during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by using our reconstructed network. Conclusions The GTRNetwork algorithm introduces the hidden layer TFA into classic relevance score-based gene regulatory network reconstruction processes. Integrating the TFA biological information with regulatory network reconstruction algorithms significantly improves both detection of new links and reduces that rate of false positives. The application of GTRNetwork on E. coli gene transcriptome data gives a set of potential regulatory links with promising biological significance for isobutanol stress and other conditions. PMID:21668997

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

PubMed Central

2011-01-01

Introduction Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. Methods MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Results Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Conclusions Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy. PMID:21888627

Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

PubMed

Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

2017-12-01

The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

Cardiovascular risk scores for coronary atherosclerosis.

PubMed

Yalcin, Murat; Kardesoglu, Ejder; Aparci, Mustafa; Isilak, Zafer; Uz, Omer; Yiginer, Omer; Ozmen, Namik; Cingozbay, Bekir Yilmaz; Uzun, Mehmet; Cebeci, Bekir Sitki

2012-10-01

The objective of this study was to compare frequently used cardiovascular risk scores in predicting the presence of coronary artery disease (CAD) and 3-vessel disease. In 350 consecutive patients (218 men and 132 women) who underwent coronary angiography, the cardiovascular risk level was determined using the Framingham Risk Score (FRS), the Modified Framingham Risk Score (MFRS), the Prospective Cardiovascular Münster (PROCAM) score, and the Systematic Coronary Risk Evaluation (SCORE). The area under the curve for receiver operating characteristic curves showed that FRS had more predictive value than the other scores for CAD (area under curve, 0.76, P < or = 0.001), but all scores had good specificity and positive predictive value. For 3-vessel disease, the FRS had better predictive value than the other scores (area under curve, 0.74, P < or = 0.001), but all scores had good specificity and negative predictive value. The risk scores (FRS, MFRS, PROCAM, and SCORE) may predict the presence and severity of coronary atherosclerosis.The FRS had better predictive value than the other scores.

Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications.

PubMed

Barth, Isabella; Schneider, Ursula; Grimm, Tobias; Karl, Alexander; Horst, David; Gaisa, Nadine T; Knüchel, Ruth; Garczyk, Stefan

2018-05-01

The stratification of bladder cancer into luminal and basal tumors has recently been introduced as a novel prognostic system in patient cohorts of muscle-invasive bladder cancer or high-grade papillary carcinomas. Using a representative immunohistochemistry panel, we analyzed luminal and basal marker expression in a large case series (n = 156) of urothelial carcinoma in situ (CIS), a precancerous lesion that frequently progresses to muscle-invasive disease. The majority of CIS cases was characterized by a positivity for luminal markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score (score of staining intensity (0-3) multiplied with percentage of positive cells (0-4)): 12, estrogen receptor (ER) β Remmele score > 2: 88% (138/156), human epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2% (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during disease progression, we compared 48 pairs of CIS and invasive tumors from the same biopsy. A highly significant loss of luminal marker expression (p < 0.001) was observed in the course of progression whereas an increase of basal marker expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of CIS cases demonstrated a positivity for at least one of the two predictive markers Her2 and ERβ, indicating that the analysis of Her2 and ERβ may help to identify CIS-patient subgroups prone to more efficient targeted treatment strategies. Larger prospective and biomarker-embedded clinical trials are needed to confirm and validate our preliminary findings.

The HIV hide and seek game: an immunogenomic analysis of the HIV epitope repertoire.

PubMed

Vider-Shalit, Tal; Almani, Michal; Sarid, Ronit; Louzoun, Yoram

2009-07-17

Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8 cytotoxic T-lymphocyte (CTL) epitopes. Here, we use bioinformatic tools to compute the HIV CTL epitope repertoire presented by over 8000 HIV sequences in multiple Human Leukocyte Antigen alleles. We define the 'Size of Immune Repertoire' (SIR) score, which represents the ratio between the number of the predicted epitopes within a protein and their expected number within a scrambled version of the same protein. We show that HIV proteins present less epitopes than expected and that the number of epitopes gradually decreases from SIV to recent HIV sequences. The decrease of the SIR score of HIV is accompanied by a high frequency of replacement mutations within epitopes. The SIR score of the different HIV proteins is not uniform. The regulatory proteins, Tat and Rev, expressed early during cellular infection have a low SIR score, whereas virion-associated genes that are expressed later, such as Env, Pol and Gag, have a higher SIR score. Actually, the SIR score of Gag keeps increasing over time. We hypothesize that our results reflect an HIV immune evasion strategy. This involves the targeting of the CTL immune response to viral structural and enzyme proteins, allowing the virus a time interval to propagate before its host cells are destroyed by CTLs. An efficient anti-HIV CTL response against HIV should thus also target the regulatory genes that HIV seeks to hide from the immune system.

The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity

PubMed Central

Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H.; Allen, Andrew S.; Goldstein, David B.

2015-01-01

Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene’s proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS), termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene’s regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1) genes that are known to cause disease through haploinsufficiency, 2) genes curated as dosage sensitive in ClinGen’s Genome Dosage Map, 3) genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4) genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding importance, ncCADD and ncGWAVA, and find both scores are significantly predictive of human dosage sensitive genes and appear to carry information beyond conservation, as assessed by ncGERP. These results highlight that the intolerance of noncoding sequence stretches in the human genome can provide a critical complementary tool to other genome annotation approaches to help identify the parts of the human genome increasingly likely to harbor mutations that influence risk of disease. PMID:26332131

High-Throughput Gene Expression Profiles to Define Drug Similarity and Predict Compound Activity.

PubMed

De Wolf, Hans; Cougnaud, Laure; Van Hoorde, Kirsten; De Bondt, An; Wegner, Joerg K; Ceulemans, Hugo; Göhlmann, Hinrich

2018-04-01

By adding biological information, beyond the chemical properties and desired effect of a compound, uncharted compound areas and connections can be explored. In this study, we add transcriptional information for 31K compounds of Janssen's primary screening deck, using the HT L1000 platform and assess (a) the transcriptional connection score for generating compound similarities, (b) machine learning algorithms for generating target activity predictions, and (c) the scaffold hopping potential of the resulting hits. We demonstrate that the transcriptional connection score is best computed from the significant genes only and should be interpreted within its confidence interval for which we provide the stats. These guidelines help to reduce noise, increase reproducibility, and enable the separation of specific and promiscuous compounds. The added value of machine learning is demonstrated for the NR3C1 and HSP90 targets. Support Vector Machine models yielded balanced accuracy values ≥80% when the expression values from DDIT4 & SERPINE1 and TMEM97 & SPR were used to predict the NR3C1 and HSP90 activity, respectively. Combining both models resulted in 22 new and confirmed HSP90-independent NR3C1 inhibitors, providing two scaffolds (i.e., pyrimidine and pyrazolo-pyrimidine), which could potentially be of interest in the treatment of depression (i.e., inhibiting the glucocorticoid receptor (i.e., NR3C1), while leaving its chaperone, HSP90, unaffected). As such, the initial hit rate increased by a factor 300, as less, but more specific chemistry could be screened, based on the upfront computed activity predictions.

Evaluation of probabilistic forecasts with the scoringRules package

NASA Astrophysics Data System (ADS)

Jordan, Alexander; Krüger, Fabian; Lerch, Sebastian

2017-04-01

Over the last decades probabilistic forecasts in the form of predictive distributions have become popular in many scientific disciplines. With the proliferation of probabilistic models arises the need for decision-theoretically principled tools to evaluate the appropriateness of models and forecasts in a generalized way in order to better understand sources of prediction errors and to improve the models. Proper scoring rules are functions S(F,y) which evaluate the accuracy of a forecast distribution F , given that an outcome y was observed. In coherence with decision-theoretical principles they allow to compare alternative models, a crucial ability given the variety of theories, data sources and statistical specifications that is available in many situations. This contribution presents the software package scoringRules for the statistical programming language R, which provides functions to compute popular scoring rules such as the continuous ranked probability score for a variety of distributions F that come up in applied work. For univariate variables, two main classes are parametric distributions like normal, t, or gamma distributions, and distributions that are not known analytically, but are indirectly described through a sample of simulation draws. For example, ensemble weather forecasts take this form. The scoringRules package aims to be a convenient dictionary-like reference for computing scoring rules. We offer state of the art implementations of several known (but not routinely applied) formulas, and implement closed-form expressions that were previously unavailable. Whenever more than one implementation variant exists, we offer statistically principled default choices. Recent developments include the addition of scoring rules to evaluate multivariate forecast distributions. The use of the scoringRules package is illustrated in an example on post-processing ensemble forecasts of temperature.

MUC1 Predicts Colorectal Cancer Metastasis: A Systematic Review and Meta-Analysis of Case Controlled Studies

PubMed Central

Lu, Minxun; Liu, Yang; Zheng, Tianying; Feng, Shijian; Hao, Meiqin; Shi, Huashan

2015-01-01

Objective To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC). Methods Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis. Results A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63–3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23–4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke’s stage (OR = 3.02, 95% CI = 2.11–4.33). No publication bias was found in the mate-analysis by Begg’s test or Egger’s test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg’s test p = 0.729, Egger’s test p = 0.000). Conclusions Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis. PMID:26367866

Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium

PubMed Central

Howat, William J; Blows, Fiona M; Provenzano, Elena; Brook, Mark N; Morris, Lorna; Gazinska, Patrycja; Johnson, Nicola; McDuffus, Leigh‐Anne; Miller, Jodi; Sawyer, Elinor J; Pinder, Sarah; van Deurzen, Carolien H M; Jones, Louise; Sironen, Reijo; Visscher, Daniel; Caldas, Carlos; Daley, Frances; Coulson, Penny; Broeks, Annegien; Sanders, Joyce; Wesseling, Jelle; Nevanlinna, Heli; Fagerholm, Rainer; Blomqvist, Carl; Heikkilä, Päivi; Ali, H Raza; Dawson, Sarah‐Jane; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli‐Matti; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W; Couch, Fergus J; Olson, Janet E; Devillee, Peter; Mesker, Wilma E; Seyaneve, Caroline M; Hollestelle, Antoinette; Benitez, Javier; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Bolla, Manjeet K; Easton, Douglas F; Schmidt, Marjanka K; Pharoah, Paul D; Sherman, Mark E

2014-01-01

Abstract Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, and large‐scale analyses are limited by the need for high throughput, standardized scoring methods. To address these limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, standardized scoring of tumour markers from multiple studies. Tissue microarray sections prepared in nine studies containing 20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen receptor, progesterone receptor), two membranous (human epidermal growth factor receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin 5/6) marker were scanned as digital images. Automated algorithms were used to score markers in tumour cells using the Ariol system. We compared automated scores against visual reads, and their associations with breast cancer survival. Approximately 65–70% of tissue microarray cores were satisfactory for scoring. Among satisfactory cores, agreement between dichotomous automated and visual scores was highest for oestrogen receptor (Kappa = 0.76), followed by human epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor (Kappa = 0.67). Automated quantitative scores for these markers were associated with hazard ratios for breast cancer mortality in a dose‐response manner. Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6 as the reference, automated scoring achieved excellent negative predictive value (96–98%), but yielded many false positives (positive predictive value = 30–32%). For all markers, we observed substantial heterogeneity in automated scoring performance across tissue microarrays. Automated analysis is a potentially useful tool for large‐scale, quantitative scoring of immunohistochemically stained tissue microarrays available in consortia. However, continued optimization, rigorous marker‐specific quality control measures and standardization of tissue microarray designs, staining and scoring protocols is needed to enhance results. PMID:27499890

Is USMLE Step 1 score a valid predictor of success in surgical residency?

PubMed

Sutton, Erica; Richardson, James David; Ziegler, Craig; Bond, Jordan; Burke-Poole, Molly; McMasters, Kelly M

2014-12-01

Many programs rely extensively on United States Medical Licensing Examination (USMLE) scores for interviews/selection of surgical residents. However, their predictive ability remains controversial. We examined the association between USMLE scores and success in surgical residency. We compared USMLE scores for 123 general surgical residents who trained in the past 20 years and their performance evaluation. Scores were normalized to the mean for the testing year and expressed as a ratio (1 = mean). Performances were evaluated by (1) rotation evaluations; (2) "dropouts;" (3) overall American Board of Surgery pass rate; (4) first-time American Board of Surgery pass rate; and (5) a retrospective comprehensive faculty evaluation. For the latter, 16 surgeons (average faculty tenure 22 years) rated residents on a 1 to 4 score (1 = fair; 4 = excellent). Rotation evaluations by faculty and "drop out" rates were not associated with USMLE score differences (dropouts had average above the mean). One hundred percent of general surgery practitioners achieved board certification regardless of USMLE score but trainees with an average above the mean had a higher first-time pass rate (P = .04). Data from the comprehensive faculty evaluations were conflicting: there was a moderate degree of correlation between board scores and faculty evaluations (r = .287, P = .001). However, a score above the mean was associated with a faculty ranking of 3 to 4 in only 51.7% of trainees. Higher USMLE scores were associated with higher faculty evaluations and first-time board pass rates. However, their positive predictive value was only 50% for higher faculty evaluations and a high overall board pass rate can be achieved regardless of USMLE scores. USMLE Step 1 score is a valid tool for selecting residents but caution might be indicated in using it as a single selection factor. Copyright © 2014 Elsevier Inc. All rights reserved.

Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia.

PubMed

Mohty, Mohamad; Szydlo, Richard M; Yong, Agnes S M; Apperley, Jane F; Goldman, John M; Melo, Junia V

2008-09-01

Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a "high" level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.

Codon usage and amino acid usage influence genes expression level.

PubMed

Paul, Prosenjit; Malakar, Arup Kumar; Chakraborty, Supriyo

2018-02-01

Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism

PubMed Central

Karagiannis, George S.; Pastoriza, Jessica M.; Wang, Yarong; Harney, Allison S.; Entenberg, David; Pignatelli, Jeanine; Sharma, Ved P.; Xue, Emily A.; Cheng, Esther; D’Alfonso, Timothy M.; Jones, Joan G.; Anampa, Jesus; Rohan, Thomas E.; Sparano, Joseph A.; Condeelis, John S.; Oktay, Maja H.

2017-01-01

Breast cancer cells disseminate through TIE2/MENACalc/MENAINV-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENAINV isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination. Chemotherapy-induced TMEM activity and cancer cell dissemination were reversed by either administration of the TIE2 inhibitor rebastinib or knockdown of the MENA gene. Our results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy. Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease. PMID:28679654

Perception of face and body expressions using electromyography, pupillometry and gaze measures.

PubMed

Kret, Mariska E; Stekelenburg, Jeroen J; Roelofs, Karin; de Gelder, Beatrice

2013-01-01

Traditional emotion theories stress the importance of the face in the expression of emotions but bodily expressions are becoming increasingly important as well. In these experiments we tested the hypothesis that similar physiological responses can be evoked by observing emotional face and body signals and that the reaction to angry signals is amplified in anxious individuals. We designed three experiments in which participants categorized emotional expressions from isolated facial and bodily expressions and emotionally congruent and incongruent face-body compounds. Participants' fixations were measured and their pupil size recorded with eye-tracking equipment and their facial reactions measured with electromyography. The results support our prediction that the recognition of a facial expression is improved in the context of a matching posture and importantly, vice versa as well. From their facial expressions, it appeared that observers acted with signs of negative emotionality (increased corrugator activity) to angry and fearful facial expressions and with positive emotionality (increased zygomaticus) to happy facial expressions. What we predicted and found, was that angry and fearful cues from the face or the body, attracted more attention than happy cues. We further observed that responses evoked by angry cues were amplified in individuals with high anxiety scores. In sum, we show that people process bodily expressions of emotion in a similar fashion as facial expressions and that the congruency between the emotional signals from the face and body facilitates the recognition of the emotion.

Perception of Face and Body Expressions Using Electromyography, Pupillometry and Gaze Measures

PubMed Central

Kret, Mariska E.; Stekelenburg, Jeroen J.; Roelofs, Karin; de Gelder, Beatrice

2013-01-01

Traditional emotion theories stress the importance of the face in the expression of emotions but bodily expressions are becoming increasingly important as well. In these experiments we tested the hypothesis that similar physiological responses can be evoked by observing emotional face and body signals and that the reaction to angry signals is amplified in anxious individuals. We designed three experiments in which participants categorized emotional expressions from isolated facial and bodily expressions and emotionally congruent and incongruent face-body compounds. Participants’ fixations were measured and their pupil size recorded with eye-tracking equipment and their facial reactions measured with electromyography. The results support our prediction that the recognition of a facial expression is improved in the context of a matching posture and importantly, vice versa as well. From their facial expressions, it appeared that observers acted with signs of negative emotionality (increased corrugator activity) to angry and fearful facial expressions and with positive emotionality (increased zygomaticus) to happy facial expressions. What we predicted and found, was that angry and fearful cues from the face or the body, attracted more attention than happy cues. We further observed that responses evoked by angry cues were amplified in individuals with high anxiety scores. In sum, we show that people process bodily expressions of emotion in a similar fashion as facial expressions and that the congruency between the emotional signals from the face and body facilitates the recognition of the emotion. PMID:23403886

Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results.

PubMed

Castelblanco, Esmeralda; Gallel, Pilar; Ros, Susana; Gatius, Sonia; Valls, Joan; De-Cubas, Aguirre A; Maliszewska, Agnieszka; Yebra-Pimentel, M Teresa; Menarguez, Javier; Gamallo, Carlos; Opocher, Giuseppe; Robledo, Mercedes; Matias-Guiu, Xavier

2012-07-01

Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies

PubMed Central

Dong, Chengliang; Wei, Peng; Jian, Xueqiu; Gibbs, Richard; Boerwinkle, Eric; Wang, Kai; Liu, Xiaoming

2015-01-01

Accurate deleteriousness prediction for nonsynonymous variants is crucial for distinguishing pathogenic mutations from background polymorphisms in whole exome sequencing (WES) studies. Although many deleteriousness prediction methods have been developed, their prediction results are sometimes inconsistent with each other and their relative merits are still unclear in practical applications. To address these issues, we comprehensively evaluated the predictive performance of 18 current deleteriousness-scoring methods, including 11 function prediction scores (PolyPhen-2, SIFT, MutationTaster, Mutation Assessor, FATHMM, LRT, PANTHER, PhD-SNP, SNAP, SNPs&GO and MutPred), 3 conservation scores (GERP++, SiPhy and PhyloP) and 4 ensemble scores (CADD, PON-P, KGGSeq and CONDEL). We found that FATHMM and KGGSeq had the highest discriminative power among independent scores and ensemble scores, respectively. Moreover, to ensure unbiased performance evaluation of these prediction scores, we manually collected three distinct testing datasets, on which no current prediction scores were tuned. In addition, we developed two new ensemble scores that integrate nine independent scores and allele frequency. Our scores achieved the highest discriminative power compared with all the deleteriousness prediction scores tested and showed low false-positive prediction rate for benign yet rare nonsynonymous variants, which demonstrated the value of combining information from multiple orthologous approaches. Finally, to facilitate variant prioritization in WES studies, we have pre-computed our ensemble scores for 87 347 044 possible variants in the whole-exome and made them publicly available through the ANNOVAR software and the dbNSFP database. PMID:25552646

Preschool speech articulation and nonword repetition abilities may help predict eventual recovery or persistence of stuttering.

PubMed

Spencer, Caroline; Weber-Fox, Christine

2014-09-01

In preschool children, we investigated whether expressive and receptive language, phonological, articulatory, and/or verbal working memory proficiencies aid in predicting eventual recovery or persistence of stuttering. Participants included 65 children, including 25 children who do not stutter (CWNS) and 40 who stutter (CWS) recruited at age 3;9-5;8. At initial testing, participants were administered the Test of Auditory Comprehension of Language, 3rd edition (TACL-3), Structured Photographic Expressive Language Test, 3rd edition (SPELT-3), Bankson-Bernthal Test of Phonology-Consonant Inventory subtest (BBTOP-CI), Nonword Repetition Test (NRT; Dollaghan & Campbell, 1998), and Test of Auditory Perceptual Skills-Revised (TAPS-R) auditory number memory and auditory word memory subtests. Stuttering behaviors of CWS were assessed in subsequent years, forming groups whose stuttering eventually persisted (CWS-Per; n=19) or recovered (CWS-Rec; n=21). Proficiency scores in morphosyntactic skills, consonant production, verbal working memory for known words, and phonological working memory and speech production for novel nonwords obtained at the initial testing were analyzed for each group. CWS-Per were less proficient than CWNS and CWS-Rec in measures of consonant production (BBTOP-CI) and repetition of novel phonological sequences (NRT). In contrast, receptive language, expressive language, and verbal working memory abilities did not distinguish CWS-Rec from CWS-Per. Binary logistic regression analysis indicated that preschool BBTOP-CI scores and overall NRT proficiency significantly predicted future recovery status. Results suggest that phonological and speech articulation abilities in the preschool years should be considered with other predictive factors as part of a comprehensive risk assessment for the development of chronic stuttering. At the end of this activity the reader will be able to: (1) describe the current status of nonlinguistic and linguistic predictors for recovery and persistence of stuttering; (2) summarize current evidence regarding the potential value of consonant cluster articulation and nonword repetition abilities in helping to predict stuttering outcome in preschool children; (3) discuss the current findings in relation to potential implications for theories of developmental stuttering; (4) discuss the current findings in relation to potential considerations for the evaluation and treatment of developmental stuttering. Copyright © 2014 Elsevier Inc. All rights reserved.

Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.

PubMed

Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun

2018-03-01

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p<0·0001), disease-free survival (HR 3·51, 2·43-5·07; p<0·0001), and overall survival (HR 3·22, 2·18-4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status. The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis. The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities. Copyright © 2018 Elsevier Ltd. All rights reserved.

A whole blood gene expression-based signature for smoking status

PubMed Central

2012-01-01

Background Smoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status. Methods Microarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite. Results Microarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53). Conclusion We have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression. PMID:23210427

MAGI2 is an independent predictor of biochemical recurrence in prostate cancer.

PubMed

David, Stephanie N; Arnold Egloff, Shanna A; Goyal, Rajen; Clark, Peter E; Phillips, Sharon; Gellert, Lan L; Hameed, Omar; Giannico, Giovanna A

2018-06-01

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology. MAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, -0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880-0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%). These results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post-operative surveillance intervals. © 2018 Wiley Periodicals, Inc.

Technical analysis of the Slosson Written Expression Test.

PubMed

Erford, Bradley T; Hofler, Donald B

2004-06-01

The Slosson Written Expression Test was designed to assess students ages 8-17 years at risk for difficulties in written expression. Scores from three independent samples were used to evaluate the test's reliability and validity for measuring students' written expression. Test-retest reliability of the SWET subscales ranged from .80 to .94 (n = 151), and .95 for the Written Expression Total Standard Scores. The median alternate-form reliability for students' Written Expression Total Standard Scores was .81 across the three forms. Scores on the Slosson test yielded concurrent validity coefficients (n = 143) of .60 with scores from the Woodcock-Johnson: Tests of Achievement-Third Edition Broad Written Language Domain and .49 with scores on the Test of Written Language-Third Edition Spontaneous Writing Quotient. Exploratory factor analytic procedures suggested the Slosson test is comprised of two dimensions, Writing Mechanics and Writing Maturity (47.1% and 20.1% variance accounted for, respectively). In general, the Slosson Written Expression Test presents with sufficient technical characteristics to be considered a useful written expression screening test.

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

PubMed Central

Bueno, Raphael; Hughes, Elisha; Wagner, Susanne; Gutin, Alexander S.; Lanchbury, Jerry S.; Zheng, Yifan; Archer, Michael A.; Gustafson, Corinne; Jones, Joshua T.; Rushton, Kristen; Saam, Jennifer; Kim, Edward; Barberis, Massimo; Wistuba, Ignacio; Wenstrup, Richard J.; Wallace, William A.; Harrison, David J.

2015-01-01

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. PMID:25396679

Using the American Board of Surgery In-Training Examination to predict board certification: a cautionary study.

PubMed

Jones, Andrew T; Biester, Thomas W; Buyske, Jo; Lewis, Frank R; Malangoni, Mark A

2014-01-01

Although designed as a low-stakes formative examination, the American Board of Surgery In-Training Examination (ABSITE) is often used in high-stakes decisions such as promotion, remediation, and retention owing to its perceived ability to predict the outcome of board certification. Because of the discrepancy between intent and use, the ability of ABSITE scores to predict passing the American Board of Surgery certification examinations was analyzed. All first-time American Board of Surgery qualifying examination (QE) examinees between 2006 and 2012 were reviewed. Examinees' postgraduate year (PGY) 1 and PGY5 ABSITE standard scores were linked to QE scores and pass/fail outcomes (n = 6912 and 6846, respectively) as well as first-time certifying examination (CE) pass/fail results (n = 1329). Linear and logistic regression analyses were performed to evaluate the utility of ABSITE scores to predict board certification scores and pass/fail outcomes. PGY1 ABSITE scores accounted for 22% of the variance in QE scores (p < 0.001). PGY5 scores were a slightly better predictor, accounting for 30% of QE score variance (p < 0.001). Analyses showed that selecting a PGY5 ABSITE score that maximized overall decision accuracy for predicting QE pass/fail outcomes (86% accuracy) resulted in 98% sensitivity, 13% specificity, a positive predictive value of 87%, and a negative predictive value of 57%. ABSITE scores were not predictive of success on the CE. ABSITE scores are a useful predictor of QE scores and outcomes but do not predict passing the CE. Although scoring well on the ABSITE is highly predictive of QE success, using low ABSITE scores to predict QE failure results in frequent decision errors. Program directors and other evaluators should use additional sources of information when making high-stakes decisions about resident performance. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

The Significance of the PD-L1 Expression in Non-Small-Cell Lung Cancer: Trenchant Double Swords as Predictive and Prognostic Markers.

PubMed

Takada, Kazuki; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Tatsuro; Maehara, Yoshihiko

2018-03-01

Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC. The PD-L1 expression on the surface of tumor cells has emerged as a potential biomarker for predicting responses to immunotherapy and prognosis after surgery in NSCLC. However, the utility of PD-L1 expression as a predictive and prognostic biomarker remains controversial because of the existence of various PD-L1 antibodies, scoring systems, and positivity cutoffs. In this review, we summarize the data from representative clinical trials of PD-1/PD-L1 immune checkpoint inhibitors in NSCLC and previous reports on the association between PD-L1 expression and clinical outcomes in patients with NSCLC. Furthermore, we discuss the future perspectives of immunotherapy and immune checkpoint factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression Analysis of p16, c-Myc, and mSin3A in Non-small Cell Lung Cancer by Computer Aided Scoring and Analysis (CASA).

PubMed

Salmaninejad, Arash; Estiar, Mehrdad Asghari; Gill, Rajbir K; Shih, Joanna H; Hewitt, Stephen; Jeon, Hyo-Sung; Fukuoka, Junya; Shilo, Konstantin; Shakoori, Abbas; Jen, Jin

2015-01-01

Immunohistochemical analysis (IHC) of tissue microarray (TMA) slides enables large sets of tissue samples to be analyzed simultaneously on a single slide. However, manual evaluation of small cores on a TMA slide is time consuming and error prone. We describe a computer aided scoring and analysis (CASA) method to allow facile and reliable scoring of IHC staining using TMA containing 300 non-small cell lung cancer (NSCLC) cases. In the two previous published papers utilizing our TMA slides of lung cancer we examined 18 proteins involved in the chromatin machinery. We developed our study using more proteins of the chromatin complex and several transcription factors that facilitate the chromatin machinery. Then, a total of 78 antibodies were evaluated by CASA to derive a normalized intensity value that correlated with the overall staining status of the targeting protein. The intensity values for TMA cores were then examined for association to clinical variables and predictive significance individually and with other factors. RESULTs: Using our TMA, the intensity of several protein pairs were significantly correlated with an increased risk of death in NSCLC. These included c-Myc with p16, mSin3A with p16 and c-Myc with mSinA. Predictive values of these pairs remained significant when evaluated based on standard IHC scores. Our results demonstrate the usefulness of CASA as a valuable tool for systematic assessment of TMA slides to identify potential predictive biomarkers using a large set of primary human tissues.

Combining Spot Sign and Intracerebral Hemorrhage Score to Estimate Functional Outcome: Analysis From the PREDICT Cohort.

PubMed

Schneider, Hauke; Huynh, Thien J; Demchuk, Andrew M; Dowlatshahi, Dar; Rodriguez-Luna, David; Silva, Yolanda; Aviv, Richard; Dzialowski, Imanuel

2018-06-01

The intracerebral hemorrhage (ICH) score is the most commonly used grading scale for stratifying functional outcome in patients with acute ICH. We sought to determine whether a combination of the ICH score and the computed tomographic angiography spot sign may improve outcome prediction in the cohort of a prospective multicenter hemorrhage trial. Prospectively collected data from 241 patients from the observational PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) were analyzed. Functional outcome at 3 months was dichotomized using the modified Rankin Scale (0-3 versus 4-6). Performance of (1) the ICH score and (2) the spot sign ICH score-a scoring scale combining ICH score and spot sign number-was tested. Multivariable analysis demonstrated that ICH score (odds ratio, 3.2; 95% confidence interval, 2.2-4.8) and spot sign number (n=1: odds ratio, 2.7; 95% confidence interval, 1.1-7.4; n>1: odds ratio, 3.8; 95% confidence interval, 1.2-17.1) were independently predictive of functional outcome at 3 months with similar odds ratios. Prediction of functional outcome was not significantly different using the spot sign ICH score compared with the ICH score alone (spot sign ICH score area under curve versus ICH score area under curve: P =0.14). In the PREDICT cohort, a prognostic score adding the computed tomographic angiography-based spot sign to the established ICH score did not improve functional outcome prediction compared with the ICH score. © 2018 American Heart Association, Inc.

Integrated Cox's model for predicting survival time of glioblastoma multiforme.

PubMed

Ai, Zhibing; Li, Longti; Fu, Rui; Lu, Jing-Min; He, Jing-Dong; Li, Sen

2017-04-01

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox's model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox's model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27 Kip1 protein, which implied the important role of p27 Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.

CLIC, a tool for expanding biological pathways based on co-expression across thousands of datasets

PubMed Central

Li, Yang; Liu, Jun S.; Mootha, Vamsi K.

2017-01-01

In recent years, there has been a huge rise in the number of publicly available transcriptional profiling datasets. These massive compendia comprise billions of measurements and provide a special opportunity to predict the function of unstudied genes based on co-expression to well-studied pathways. Such analyses can be very challenging, however, since biological pathways are modular and may exhibit co-expression only in specific contexts. To overcome these challenges we introduce CLIC, CLustering by Inferred Co-expression. CLIC accepts as input a pathway consisting of two or more genes. It then uses a Bayesian partition model to simultaneously partition the input gene set into coherent co-expressed modules (CEMs), while assigning the posterior probability for each dataset in support of each CEM. CLIC then expands each CEM by scanning the transcriptome for additional co-expressed genes, quantified by an integrated log-likelihood ratio (LLR) score weighted for each dataset. As a byproduct, CLIC automatically learns the conditions (datasets) within which a CEM is operative. We implemented CLIC using a compendium of 1774 mouse microarray datasets (28628 microarrays) or 1887 human microarray datasets (45158 microarrays). CLIC analysis reveals that of 910 canonical biological pathways, 30% consist of strongly co-expressed gene modules for which new members are predicted. For example, CLIC predicts a functional connection between protein C7orf55 (FMC1) and the mitochondrial ATP synthase complex that we have experimentally validated. CLIC is freely available at www.gene-clic.org. We anticipate that CLIC will be valuable both for revealing new components of biological pathways as well as the conditions in which they are active. PMID:28719601

[PD-L1 expression: An emerging biomarker in non-small cell lung cancer].

PubMed

Adam, Julien; Planchard, David; Marabelle, Aurélien; Soria, Jean-Charles; Scoazec, Jean-Yves; Lantuéjoul, Sylvie

2016-01-01

Therapies targeting immune checkpoints, in particular programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1), are major new strategies for the treatment of several malignancies including mestatatic non-small cell lung cancer (NSCLC). The identification of predictive biomarkers of response is required, considering efficacy, cost and potential adverse events. Expression of PD-L1 by immunohistochemistry has been associated with higher response rate and overall survival in several clinical trials evaluating anti-PD-1 and anti-PD-L1 monoclonal antibodies. Thus, PD-L1 immunohistochemical companion assays could be required for treatment with some of these therapies in NSCLC. However, heterogeneity in methodologies of PD-L1 assays in terms of primary antibodies and scoring algorithms, and tumor heterogenity for PD-L1 expression are important issues to be considered. More studies are required to compare the different assays, ensure their harmonization and standardization and identify the optimal conditions for testing. PD-L1 expression is likely an imperfect predictive biomarker for patient selection and association with other markers of the tumor immune microenvironment will be probably necessary in the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and Scoring in Lead Optimization.

PubMed

Crespo, Alejandro; Rodriguez-Granillo, Agustina; Lim, Victoria T

2017-01-01

The development and application of quantum mechanics (QM) methodologies in computer- aided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only a few examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed. In addition, we introduce and validate a simplified QM/MM expression to compute protein-ligand binding energies. Overall, QMbased scoring functions are generally better to predict ligand affinities than those based on classical mechanics. However, the agreement between experimental activities and calculated binding energies is highly dependent on the specific chemical series considered. The advantage of more accurate QM methods is evident in cases where charge transfer and polarization effects are important, for example when metals are involved in the binding process or when dispersion forces play a significant role as in the case of hydrophobic or stacking interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Limited potential of genetic predisposition scores to predict muscle mass and strength performance in Flemish Caucasians between 19 and 73 years of age.

PubMed

Charlier, Ruben; Caspers, Maarten; Knaeps, Sara; Mertens, Evelien; Lambrechts, Diether; Lefevre, Johan; Thomis, Martine

2017-03-01

Since both muscle mass and strength performance are polygenic in nature, the current study compared four genetic predisposition scores (GPS) in their ability to predict these phenotypes. Data were gathered within the framework of the first-generation Flemish Policy Research Centre "Sport, Physical Activity and Health" (2002-2004). Results are based on muscle characteristics data of 565 Flemish Caucasians (19-73 yr, 365 men). Skeletal muscle mass was determined from bioelectrical impedance. The Biodex dynamometer was used to measure isometric (PT static120° ) and isokinetic strength (PT dynamic60° and PT dynamic240° ), ballistic movement speed (S 20% ), and muscular endurance (Work) of the knee extensors. Genotyping was done for 153 gene variants, selected on the basis of a literature search and the expression quantitative trait loci of selected genes. Four GPS were designed: a total GPS (based on the sum of all 153 variants, each favorable allele = score 1), a data-driven and weighted GPS [respectively, the sum of favorable alleles of those variants with significant b-coefficients in stepwise regression (GPS dd ), and the sum of these variants weighted with their respective partial r 2 (GPS w )], and an elastic net GPS (based on the variants that were selected by an elastic net regularization; GPS en ). It was found that four different models for a GPS were able to significantly predict up to ~7% of the variance in strength performance. GPS en made the best prediction of SMM and Work. However, this was not the case for the remaining strength performance parameters, where best predictions were made by GPS dd and GPS w . Copyright © 2017 the American Physiological Society.

Antibody validation and scoring guidelines for ABCG2 immunohistochemical staining in formalin-fixed paraffin-embedded colon cancer tissue

PubMed Central

Cederbye, Camilla Natasha; Palshof, Jesper Andreas; Hansen, Tine Plato; Duun-Henriksen, Anne Katrine; Linnemann, Dorte; Stenvang, Jan; Nielsen, Dorte Lisbet; Brünner, Nils; Viuff, Birgitte Martine

2016-01-01

Overexpression of the ATP-dependent drug efflux pump ABCG2 is a major molecular mechanism of multidrug resistance in cancer and might be a predictive biomarker for drug response. Contradictory results have been reported for immunohistochemical studies of ABCG2 protein expression in colorectal cancer (CRC), probably because of the use of different antibodies and scoring approaches. In this study, we systematically studied six commercially available anti-ABCG2 antibodies, using cell lines with up-regulation of ABCG2, and selected one antibody for validation in CRC tissue. Furthermore, we established scoring guidelines for ABCG2 expression based on the clinically used guidelines for HER2 immunohistochemistry assessment in gastric cancer. The guidelines provide a semi-quantitative measure of the basolateral membrane staining of ABCG2 and disregard the apical membrane staining and the cytoplasmic signal. Intra-tumor heterogeneity in ABCG2 immunoreactivity was observed; however, statistical analyses of tissue microarrays (TMAs) and the corresponding whole sections from primary tumors of 57 metastatic CRC patients revealed a strong positive correlation between maximum TMA scores and whole sections, especially when more than one core was used. In conclusion, here, we provide validated results to guide future studies on the associations between ABCG2 immunoreactivity in tumor cells and the benefits of chemotherapeutic treatment in patients with CRC. PMID:27257141

Gene-Expression Signature Predicts Postoperative Recurrence in Stage I Non-Small Cell Lung Cancer Patients

PubMed Central

Lu, Yan; Wang, Liang; Liu, Pengyuan; Yang, Ping; You, Ming

2012-01-01

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset −142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = −0.83, P<1e-16) and this signature was validated in four independent datasets with AUC >85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients. PMID:22292069

A Filter Feature Selection Method Based on MFA Score and Redundancy Excluding and It's Application to Tumor Gene Expression Data Analysis.

PubMed

Li, Jiangeng; Su, Lei; Pang, Zenan

2015-12-01

Feature selection techniques have been widely applied to tumor gene expression data analysis in recent years. A filter feature selection method named marginal Fisher analysis score (MFA score) which is based on graph embedding has been proposed, and it has been widely used mainly because it is superior to Fisher score. Considering the heavy redundancy in gene expression data, we proposed a new filter feature selection technique in this paper. It is named MFA score+ and is based on MFA score and redundancy excluding. We applied it to an artificial dataset and eight tumor gene expression datasets to select important features and then used support vector machine as the classifier to classify the samples. Compared with MFA score, t test and Fisher score, it achieved higher classification accuracy.

Cross-cultural validity of the scale for interpersonal behavior.

PubMed

Nota, Laura; Arrindell, Willem A; Soresi, Salvatore; van der Ende, Jan; Sanavio, Ezio

2011-01-01

The Scale for Interpersonal Behavior (SIB) is a 50-item multidimensional measure of difficulty and distress in assertiveness. The SIB assesses negative assertion, expression of and dealing with personal limitations, initiating assertiveness and positive assertion. The SIB was originally developed in the Netherlands. The present study attempted to replicate the original factors with an Italian student sample (n = 995). The four distress and four performance factors were replicable across two methods of analysis (the multiple group method of confirmatory analysis and Tucker's coefficient of congruence (phi). The corresponding scales were internally consistent and showed predicted patterns of correlations with a measure of self-efficacy. Sex and age differences in assertiveness were generally negligible. Italian students had higher positive assertion-performance scores than the Dutch and comparable scores on other performance scales; by contrast, the Italian subjects had significantly higher scores on all SIB distress scales than their Dutch equivalents. This was ascribed to the stronger pressure on people in Italian society to behave assertively (Hofstede's National Masculinity score = 70) as opposed to the Dutch society (National Masculinity score = 14).

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding

PubMed Central

Camus, Marine; Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O.; Jutabha, Rome; Ghassemi, Kevin A.; Machicado, Gustavo A.; Dulai, Gareth S.; Jensen, Mary Ellen; Gornbein, Jeffrey A.

2014-01-01

Background & aims Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper GIB. The aim of our study was to compare the accuracies of 3 different prognostic scores (CURE Hemostasis prognosis score, Charlston index and ASA score) for the prediction of 30 day rebleeding, surgery and death in severe LGIB. Methods Data on consecutive patients hospitalized with severe GI bleeding from January 2006 to October 2011 in our two-tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies and area under the receiver operating characteristic (AUROC) were computed for three scores for predictions of rebleeding, surgery and mortality at 30 days. Results 235 consecutive patients with LGIB were included between 2006 and 2011. 23% of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%) whereas the CURE Hemostasis prognosis score and the Charlson index both had accuracies less than 75% for the prediction of death within 30 days. Conclusions ASA score could be useful to predict death within 30 days. However a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery and death) in LGIB. PMID:25599218

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

PubMed Central

2010-01-01

Background The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer. Trial Registration Current Controlled Trials: NCT00004205 PMID:20144231

Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

PubMed

Martyanov, Viktor; Whitfield, Michael L

2016-01-01

The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

Unmasking Upstream Gene Expression Regulators with miRNA-corrected mRNA Data

PubMed Central

Bollmann, Stephanie; Bu, Dengpan; Wang, Jiaqi; Bionaz, Massimo

2015-01-01

Expressed micro-RNA (miRNA) affects messenger RNA (mRNA) abundance, hindering the accuracy of upstream regulator analysis. Our objective was to provide an algorithm to correct such bias. Large mRNA and miRNA analyses were performed on RNA extracted from bovine liver and mammary tissue. Using four levels of target scores from TargetScan (all miRNA:mRNA target gene pairs or only the top 25%, 50%, or 75%). Using four levels of target scores from TargetScan (all miRNA:mRNA target gene pairs or only the top 25%, 50%, or 75%) and four levels of the magnitude of miRNA effect (ME) on mRNA expression (30%, 50%, 75%, and 83% mRNA reduction), we generated 17 different datasets (including the original dataset). For each dataset, we performed upstream regulator analysis using two bioinformatics tools. We detected an increased effect on the upstream regulator analysis with larger miRNA:mRNA pair bins and higher ME. The miRNA correction allowed identification of several upstream regulators not present in the analysis of the original dataset. Thus, the proposed algorithm improved the prediction of upstream regulators. PMID:27279737

ROCK I Has More Accurate Prognostic Value than MET in Predicting Patient Survival in Colorectal Cancer.

PubMed

Li, Jian; Bharadwaj, Shruthi S; Guzman, Grace; Vishnubhotla, Ramana; Glover, Sarah C

2015-06-01

Colorectal cancer remains the second leading cause of death in the United States despite improvements in incidence rates and advancements in screening. The present study evaluated the prognostic value of two tumor markers, MET and ROCK I, which have been noted in other cancers to provide more accurate prognoses of patient outcomes than tumor staging alone. We constructed a tissue microarray from surgical specimens of adenocarcinomas from 108 colorectal cancer patients. Using immunohistochemistry, we examined the expression levels of tumor markers MET and ROCK I, with a pathologist blinded to patient identities and clinical outcomes providing the scoring of MET and ROCK I expression. We then used retrospective analysis of patients' survival data to provide correlations with expression levels of MET and ROCK I. Both MET and ROCK I were significantly over-expressed in colorectal cancer tissues, relative to the unaffected adjacent mucosa. Kaplan-Meier survival analysis revealed that patients' 5-year survival was inversely correlated with levels of expression of ROCK I. In contrast, MET was less strongly correlated with five-year survival. ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression. As a result, ROCK I may provide a less invasive method of assessing patient prognoses and directing therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

AUCTSP: an improved biomarker gene pair class predictor.

PubMed

Kagaris, Dimitri; Khamesipour, Alireza; Yiannoutsos, Constantin T

2018-06-26

The Top Scoring Pair (TSP) classifier, based on the concept of relative ranking reversals in the expressions of pairs of genes, has been proposed as a simple, accurate, and easily interpretable decision rule for classification and class prediction of gene expression profiles. The idea that differences in gene expression ranking are associated with presence or absence of disease is compelling and has strong biological plausibility. Nevertheless, the TSP formulation ignores significant available information which can improve classification accuracy and is vulnerable to selecting genes which do not have differential expression in the two conditions ("pivot" genes). We introduce the AUCTSP classifier as an alternative rank-based estimator of the magnitude of the ranking reversals involved in the original TSP. The proposed estimator is based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) and as such, takes into account the separation of the entire distribution of gene expression levels in gene pairs under the conditions considered, as opposed to comparing gene rankings within individual subjects as in the original TSP formulation. Through extensive simulations and case studies involving classification in ovarian, leukemia, colon, breast and prostate cancers and diffuse large b-cell lymphoma, we show the superiority of the proposed approach in terms of improving classification accuracy, avoiding overfitting and being less prone to selecting non-informative (pivot) genes. The proposed AUCTSP is a simple yet reliable and robust rank-based classifier for gene expression classification. While the AUCTSP works by the same principle as TSP, its ability to determine the top scoring gene pair based on the relative rankings of two marker genes across all subjects as opposed to each individual subject results in significant performance gains in classification accuracy. In addition, the proposed method tends to avoid selection of non-informative (pivot) genes as members of the top-scoring pair.

Recognition of facial emotion and perceived parental bonding styles in healthy volunteers and personality disorder patients.

PubMed

Zheng, Leilei; Chai, Hao; Chen, Wanzhen; Yu, Rongrong; He, Wei; Jiang, Zhengyan; Yu, Shaohua; Li, Huichun; Wang, Wei

2011-12-01

Early parental bonding experiences play a role in emotion recognition and expression in later adulthood, and patients with personality disorder frequently experience inappropriate parental bonding styles, therefore the aim of the present study was to explore whether parental bonding style is correlated with recognition of facial emotion in personality disorder patients. The Parental Bonding Instrument (PBI) and the Matsumoto and Ekman Japanese and Caucasian Facial Expressions of Emotion (JACFEE) photo set tests were carried out in 289 participants. Patients scored lower on parental Care but higher on parental Freedom Control and Autonomy Denial subscales, and they displayed less accuracy when recognizing contempt, disgust and happiness than the healthy volunteers. In healthy volunteers, maternal Autonomy Denial significantly predicted accuracy when recognizing fear, and maternal Care predicted the accuracy of recognizing sadness. In patients, paternal Care negatively predicted the accuracy of recognizing anger, paternal Freedom Control predicted the perceived intensity of contempt, maternal Care predicted the accuracy of recognizing sadness, and the intensity of disgust. Parenting bonding styles have an impact on the decoding process and sensitivity when recognizing facial emotions, especially in personality disorder patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

New methods for analyzing semantic graph based assessments in science education

NASA Astrophysics Data System (ADS)

Vikaros, Lance Steven

This research investigated how the scoring of semantic graphs (known by many as concept maps) could be improved and automated in order to address issues of inter-rater reliability and scalability. As part of the NSF funded SENSE-IT project to introduce secondary school science students to sensor networks (NSF Grant No. 0833440), semantic graphs illustrating how temperature change affects water ecology were collected from 221 students across 16 schools. The graphing task did not constrain students' use of terms, as is often done with semantic graph based assessment due to coding and scoring concerns. The graphing software used provided real-time feedback to help students learn how to construct graphs, stay on topic and effectively communicate ideas. The collected graphs were scored by human raters using assessment methods expected to boost reliability, which included adaptations of traditional holistic and propositional scoring methods, use of expert raters, topical rubrics, and criterion graphs. High levels of inter-rater reliability were achieved, demonstrating that vocabulary constraints may not be necessary after all. To investigate a new approach to automating the scoring of graphs, thirty-two different graph features characterizing graphs' structure, semantics, configuration and process of construction were then used to predict human raters' scoring of graphs in order to identify feature patterns correlated to raters' evaluations of graphs' topical accuracy and complexity. Results led to the development of a regression model able to predict raters' scoring with 77% accuracy, with 46% accuracy expected when used to score new sets of graphs, as estimated via cross-validation tests. Although such performance is comparable to other graph and essay based scoring systems, cross-context testing of the model and methods used to develop it would be needed before it could be recommended for widespread use. Still, the findings suggest techniques for improving the reliability and scalability of semantic graph based assessments without requiring constraint of how ideas are expressed.

Effects of onboard insecticide use on airline flight attendants.

PubMed

Kilburn, Kaye H

2004-06-01

Flight attendants (FAs) exposed to insecticide spray in an aircraft were compared with unexposed subjects for neurobehavioral function, pulmonary function, mood states, and symptoms. The 33 symptomatic FAs were self-selected, and 5 had retired for disability. Testing procedures included balance, reaction time, color discrimination, visual fields, grip strength, verbal recall, problem solving, attention and discrimination functions, and long-term memory functions. Measurements were expressed as a percentage of their predicted values (derived from unexposed controls), and the author compared the means of the percentage predicted values by analysis of variance. Symptom frequencies and Profile of Mood States (POMS) scores were assessed. FAs were significantly more impaired than controls with respect to balance with eyes closed, grip strength, and color discrimination. Nearly half had 3 or more abnormal neurobehavioral functions, after adjustment was made for age, sex, and education level. Neither elevated POMS scores nor frequencies of average symptoms correlated with their numbers of abnormal measurements. Occupational exposure to synthetic pyrethrin insecticides on airliners was associated with neurobehavioral impairment and disability retirement.

Predicting Aggressive Tendencies by Visual Attention Bias Associated with Hostile Emotions

PubMed Central

Lin, Ping-I; Hsieh, Cheng-Da; Juan, Chi-Hung; Hossain, Md Monir; Erickson, Craig A.; Lee, Yang-Han; Su, Mu-Chun

2016-01-01

The goal of the current study is to clarify the relationship between social information processing (e.g., visual attention to cues of hostility, hostility attribution bias, and facial expression emotion labeling) and aggressive tendencies. Thirty adults were recruited in the eye-tracking study that measured various components in social information processing. Baseline aggressive tendencies were measured using the Buss-Perry Aggression Questionnaire (AQ). Visual attention towards hostile objects was measured as the proportion of eye gaze fixation duration on cues of hostility. Hostility attribution bias was measured with the rating results for emotions of characters in the images. The results show that the eye gaze duration on hostile characters was significantly inversely correlated with the AQ score and less eye contact with an angry face. The eye gaze duration on hostile object was not significantly associated with hostility attribution bias, although hostility attribution bias was significantly positively associated with the AQ score. Our findings suggest that eye gaze fixation time towards non-hostile cues may predict aggressive tendencies. PMID:26901770

Predicting Aggressive Tendencies by Visual Attention Bias Associated with Hostile Emotions.

PubMed

Lin, Ping-I; Hsieh, Cheng-Da; Juan, Chi-Hung; Hossain, Md Monir; Erickson, Craig A; Lee, Yang-Han; Su, Mu-Chun

2016-01-01

The goal of the current study is to clarify the relationship between social information processing (e.g., visual attention to cues of hostility, hostility attribution bias, and facial expression emotion labeling) and aggressive tendencies. Thirty adults were recruited in the eye-tracking study that measured various components in social information processing. Baseline aggressive tendencies were measured using the Buss-Perry Aggression Questionnaire (AQ). Visual attention towards hostile objects was measured as the proportion of eye gaze fixation duration on cues of hostility. Hostility attribution bias was measured with the rating results for emotions of characters in the images. The results show that the eye gaze duration on hostile characters was significantly inversely correlated with the AQ score and less eye contact with an angry face. The eye gaze duration on hostile object was not significantly associated with hostility attribution bias, although hostility attribution bias was significantly positively associated with the AQ score. Our findings suggest that eye gaze fixation time towards non-hostile cues may predict aggressive tendencies.

Predicting Internet risks: a longitudinal panel study of gratifications-sought, Internet addiction symptoms, and social media use among children and adolescents

PubMed Central

Leung, Louis

2014-01-01

This study used longitudinal panel survey data collected from 417 adolescents at 2 points in time 1 year apart. It examined relationships between Internet risks changes in Time 2 and social media gratifications-sought, Internet addiction symptoms, and social media use all measured at Time 1. By controlling for age, gender, education, and criterion variable scores in Internet addiction at Time 1, entertainment and instant messaging use at Time 1 significantly predicted increased Internet addiction measured at Time 2. The study also controlled for demographics and scores of criterion variables in Internet risks: targeted for harassment, privacy exposed, and pornographic or violent content consumed in Time 1. Gratifications-sought (including status-gaining, expressing opinions, and identity experimentation), Internet addiction symptoms (including withdrawal and negative life consequences), and social media use (in particular, blogs, and Facebook) significantly predicted Internet risk changes in Time 2. These findings suggest that, with their predictive power, these predictors at Time 1 could be used to identify those adolescents who are likely to develop Internet addiction symptoms and the likelihood of experiencing Internet risks based on their previous gratifications-sought, previous addiction symptoms, and their habits of social media use at Time 1. PMID:25750792

Pathological Gleason prediction through gland ring morphometry in immunofluorescent prostate cancer images

NASA Astrophysics Data System (ADS)

Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

2016-03-01

The Gleason score is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous quantitative techniques developed to approximate and duplicate the Gleason scoring system. Most of these approaches have been developed in standard H and E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. In this work we leverage a new method of segmenting gland rings in IF images for predicting the pathological Gleason; both the clinical and the image specific grade, which may not necessarily be the same. We combine these measures with nuclear specific characteristics as assessed by the MST algorithm. Our individual features correlate well univariately with the Gleason grades, and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes (CI of 0.89), significantly outperforming the clinical Gleason grades (CI of 0.78). This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade.

Predicting Internet risks: a longitudinal panel study of gratifications-sought, Internet addiction symptoms, and social media use among children and adolescents.

PubMed

Leung, Louis

2014-01-01

This study used longitudinal panel survey data collected from 417 adolescents at 2 points in time 1 year apart. It examined relationships between Internet risks changes in Time 2 and social media gratifications-sought, Internet addiction symptoms, and social media use all measured at Time 1. By controlling for age, gender, education, and criterion variable scores in Internet addiction at Time 1, entertainment and instant messaging use at Time 1 significantly predicted increased Internet addiction measured at Time 2. The study also controlled for demographics and scores of criterion variables in Internet risks: targeted for harassment, privacy exposed, and pornographic or violent content consumed in Time 1. Gratifications-sought (including status-gaining, expressing opinions, and identity experimentation), Internet addiction symptoms (including withdrawal and negative life consequences), and social media use (in particular, blogs, and Facebook) significantly predicted Internet risk changes in Time 2. These findings suggest that, with their predictive power, these predictors at Time 1 could be used to identify those adolescents who are likely to develop Internet addiction symptoms and the likelihood of experiencing Internet risks based on their previous gratifications-sought, previous addiction symptoms, and their habits of social media use at Time 1.

Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study.

PubMed

Stanley, Adrian J; Laine, Loren; Dalton, Harry R; Ngu, Jing H; Schultz, Michael; Abazi, Roseta; Zakko, Liam; Thornton, Susan; Wilkinson, Kelly; Khor, Cristopher J L; Murray, Iain A; Laursen, Stig B

2017-01-04

 To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding.  International multicentre prospective study.  Six large hospitals in Europe, North America, Asia, and Oceania.  3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding.  Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined.  The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay.  The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited.Trial registration Current Controlled Trials ISRCTN16235737. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of Voice Acoustics as Predictors of Clinical Depression Scores.

PubMed

Hashim, Nik Wahidah; Wilkes, Mitch; Salomon, Ronald; Meggs, Jared; France, Daniel J

2017-03-01

The aim of the present study was to determine if acoustic measures of voice, characterizing specific spectral and timing properties, predict clinical ratings of depression severity measured in a sample of patients using the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI-II). This is a prospective study. Voice samples and clinical depression scores were collected prospectively from consenting adult patients who were referred to psychiatry from the adult emergency department or primary care clinics. The patients were audio-recorded as they read a standardized passage in a nearly closed-room environment. Mean Absolute Error (MAE) between actual and predicted depression scores was used as the primary outcome measure. The average MAE between predicted and actual HAMD scores was approximately two scores for both men and women, and the MAE for the BDI-II scores was approximately one score for men and eight scores for women. Timing features were predictive of HAMD scores in female patients while a combination of timing features and spectral features was predictive of scores in male patients. Timing features were predictive of BDI-II scores in male patients. Voice acoustic features extracted from read speech demonstrated variable effectiveness in predicting clinical depression scores in men and women. Voice features were highly predictive of HAMD scores in men and women, and BDI-II scores in men, respectively. The methodology is feasible for diagnostic applications in diverse clinical settings as it can be implemented during a standard clinical interview in a normal closed room and without strict control on the recording environment. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Pathway-based personalized analysis of cancer

PubMed Central

Drier, Yotam; Sheffer, Michal; Domany, Eytan

2013-01-01

We introduce Pathifier, an algorithm that infers pathway deregulation scores for each tumor sample on the basis of expression data. This score is determined, in a context-specific manner, for every particular dataset and type of cancer that is being investigated. The algorithm transforms gene-level information into pathway-level information, generating a compact and biologically relevant representation of each sample. We demonstrate the algorithm’s performance on three colorectal cancer datasets and two glioblastoma multiforme datasets and show that our multipathway-based representation is reproducible, preserves much of the original information, and allows inference of complex biologically significant information. We discovered several pathways that were significantly associated with survival of glioblastoma patients and two whose scores are predictive of survival in colorectal cancer: CXCR3-mediated signaling and oxidative phosphorylation. We also identified a subclass of proneural and neural glioblastoma with significantly better survival, and an EGF receptor-deregulated subclass of colon cancers. PMID:23547110

Simple prediction scores predict good and devastating outcomes after stroke more accurately than physicians.

PubMed

Reid, John Michael; Dai, Dingwei; Delmonte, Susanna; Counsell, Carl; Phillips, Stephen J; MacLeod, Mary Joan

2017-05-01

physicians are often asked to prognosticate soon after a patient presents with stroke. This study aimed to compare two outcome prediction scores (Five Simple Variables [FSV] score and the PLAN [Preadmission comorbidities, Level of consciousness, Age, and focal Neurologic deficit]) with informal prediction by physicians. demographic and clinical variables were prospectively collected from consecutive patients hospitalised with acute ischaemic or haemorrhagic stroke (2012-13). In-person or telephone follow-up at 6 months established vital and functional status (modified Rankin score [mRS]). Area under the receiver operating curves (AUC) was used to establish prediction score performance. five hundred and seventy-five patients were included; 46% female, median age 76 years, 88% ischaemic stroke. Six months after stroke, 47% of patients had a good outcome (alive and independent, mRS 0-2) and 26% a devastating outcome (dead or severely dependent, mRS 5-6). The FSV and PLAN scores were superior to physician prediction (AUCs of 0.823-0.863 versus 0.773-0.805, P < 0.0001) for good and devastating outcomes. The FSV score was superior to the PLAN score for predicting good outcomes and vice versa for devastating outcomes (P < 0.001). Outcome prediction was more accurate for those with later presentations (>24 hours from onset). the FSV and PLAN scores are validated in this population for outcome prediction after both ischaemic and haemorrhagic stroke. The FSV score is the least complex of all developed scores and can assist outcome prediction by physicians. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

The influence of gene expression profiling on decisional conflict in decision making for early-stage breast cancer chemotherapy.

PubMed

MacDonald, Karen V; Bombard, Yvonne; Deal, Ken; Trudeau, Maureen; Leighl, Natasha; Marshall, Deborah A

2016-07-01

Women with early-stage breast cancer, of whom only 15% will experience a recurrence, are often conflicted or uncertain about taking chemotherapy. Gene expression profiling (GEP) of tumours informs risk prediction, potentially affecting treatment decisions. We examined whether receiving a GEP test score reduces decisional conflict in chemotherapy treatment decision making. A general population sample of 200 women completed the decisional conflict scale (DCS) at baseline (no GEP test score scenario) and after (scenario with GEP test score added) completing a discrete choice experiment survey for early-stage breast cancer chemotherapy. We scaled the 16-item DCS total scores and subscores from 0 to 100 and calculated means, standard deviations and change in scores, with significance (p < 0.05) based on matched pairs t-tests. We identified five respondent subgroups based on preferred treatment option; almost 40% did not change their chemotherapy decision after receiving GEP testing information. Total score and all subscores (uncertainty, informed, values clarity, support, and effective decision) decreased significantly in the respondent subgroup who were unsure about taking chemotherapy initially but changed to no chemotherapy (n =33). In the subgroup of respondents (n = 25) who chose chemotherapy initially but changed to unsure, effective decision subscore increased significantly. In the overall sample, changes in total and all subscores were non-significant. GEP testing adds value for women initially unsure about chemotherapy treatment with a decrease in decisional conflict. However, for women who are confident about their treatment decisions, GEP testing may not add value. Decisions to request GEP testing should be personalised based on patient preferences. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of Predicted Paths for ACT Aspire Score Reports. WP-2014-06

ERIC Educational Resources Information Center

Allen, Jeff

2014-01-01

This report focuses on the initial development of the predicted score paths for ACT Aspire reporting. The paths provide predicted score ranges for the next two years--as well as predicted ACT score ranges for tests administered at grades 9 and 10. Longitudinal ACT Aspire data for students tested in spring 2013 and spring 2014, as well as…

Scoring systems for outcome prediction in patients with perforated peptic ulcer.

PubMed

Thorsen, Kenneth; Søreide, Jon Arne; Søreide, Kjetil

2013-04-10

Patients with perforated peptic ulcer (PPU) often present with acute, severe illness that carries a high risk for morbidity and mortality. Mortality ranges from 3-40% and several prognostic scoring systems have been suggested. The aim of this study was to review the available scoring systems for PPU patients, and to assert if there is evidence to prefer one to the other. We searched PubMed for the mesh terms "perforated peptic ulcer", "scoring systems", "risk factors", "outcome prediction", "mortality", "morbidity" and the combinations of these terms. In addition to relevant scores introduced in the past (e.g. Boey score), we included recent studies published between January 2000 and December 2012) that reported on scoring systems for prediction of morbidity and mortality in PPU patients. A total of ten different scoring systems used to predict outcome in PPU patients were identified; the Boey score, the Hacettepe score, the Jabalpur score the peptic ulcer perforation (PULP) score, the ASA score, the Charlson comorbidity index, the sepsis score, the Mannheim Peritonitis Index (MPI), the Acute physiology and chronic health evaluation II (APACHE II), the simplified acute physiology score II (SAPS II), the Mortality probability models II (MPM II), the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity physical sub-score (POSSUM-phys score). Only four of the scores were specifically constructed for PPU patients. In five studies the accuracy of outcome prediction of different scoring systems was evaluated by receiver operating characteristics curve (ROC) analysis, and the corresponding area under the curve (AUC) among studies compared. Considerable variation in performance both between different scores and between different studies was found, with the lowest and highest AUC reported between 0.63 and 0.98, respectively. While the Boey score and the ASA score are most commonly used to predict outcome for PPU patients, considerable variations in accuracy for outcome prediction were shown. Other scoring systems are hampered by a lack of validation or by their complexity that precludes routine clinical use. While the PULP score seems promising it needs external validation before widespread use.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding.

PubMed

Camus, Marine; Jensen, Dennis M; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S; Jensen, Mary E; Gornbein, Jeffrey A

2016-01-01

Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.

Automated Clinical Assessment from Smart home-based Behavior Data

PubMed Central

Dawadi, Prafulla Nath; Cook, Diane Joyce; Schmitter-Edgecombe, Maureen

2016-01-01

Smart home technologies offer potential benefits for assisting clinicians by automating health monitoring and well-being assessment. In this paper, we examine the actual benefits of smart home-based analysis by monitoring daily behaviour in the home and predicting standard clinical assessment scores of the residents. To accomplish this goal, we propose a Clinical Assessment using Activity Behavior (CAAB) approach to model a smart home resident’s daily behavior and predict the corresponding standard clinical assessment scores. CAAB uses statistical features that describe characteristics of a resident’s daily activity performance to train machine learning algorithms that predict the clinical assessment scores. We evaluate the performance of CAAB utilizing smart home sensor data collected from 18 smart homes over two years using prediction and classification-based experiments. In the prediction-based experiments, we obtain a statistically significant correlation (r = 0.72) between CAAB-predicted and clinician-provided cognitive assessment scores and a statistically significant correlation (r = 0.45) between CAAB-predicted and clinician-provided mobility scores. Similarly, for the classification-based experiments, we find CAAB has a classification accuracy of 72% while classifying cognitive assessment scores and 76% while classifying mobility scores. These prediction and classification results suggest that it is feasible to predict standard clinical scores using smart home sensor data and learning-based data analysis. PMID:26292348

In-hospital risk prediction for post-stroke depression: development and validation of the Post-stroke Depression Prediction Scale.

PubMed

de Man-van Ginkel, Janneke M; Hafsteinsdóttir, Thóra B; Lindeman, Eline; Ettema, Roelof G A; Grobbee, Diederick E; Schuurmans, Marieke J

2013-09-01

The timely detection of post-stroke depression is complicated by a decreasing length of hospital stay. Therefore, the Post-stroke Depression Prediction Scale was developed and validated. The Post-stroke Depression Prediction Scale is a clinical prediction model for the early identification of stroke patients at increased risk for post-stroke depression. The study included 410 consecutive stroke patients who were able to communicate adequately. Predictors were collected within the first week after stroke. Between 6 to 8 weeks after stroke, major depressive disorder was diagnosed using the Composite International Diagnostic Interview. Multivariable logistic regression models were fitted. A bootstrap-backward selection process resulted in a reduced model. Performance of the model was expressed by discrimination, calibration, and accuracy. The model included a medical history of depression or other psychiatric disorders, hypertension, angina pectoris, and the Barthel Index item dressing. The model had acceptable discrimination, based on an area under the receiver operating characteristic curve of 0.78 (0.72-0.85), and calibration (P value of the U-statistic, 0.96). Transforming the model to an easy-to-use risk-assessment table, the lowest risk category (sum score, <-10) showed a 2% risk of depression, which increased to 82% in the highest category (sum score, >21). The clinical prediction model enables clinicians to estimate the degree of the depression risk for an individual patient within the first week after stroke.

Measuring ability to enhance and suppress emotional expression: The Flexible Regulation of Emotional Expression (FREE) Scale.

PubMed

Burton, Charles L; Bonanno, George A

2016-08-01

Flexibility in self-regulatory behaviors has proved to be an important quality for adjusting to stressful life events and requires individuals to have a diverse repertoire of emotion regulation abilities. However, the most commonly used emotion regulation questionnaires assess frequency of behavior rather than ability, with little evidence linking these measures to observable capacity to enact a behavior. The aim of the current investigation was to develop and validate a Flexible Regulation of Emotional Expression (FREE) Scale that measures a person's ability to enhance and suppress displayed emotion across an array of hypothetical contexts. In Studies 1 and 2, a series of confirmatory factor analyses revealed that the FREE Scale consists of 4 first-order factors divided by regulation and emotional valence type that can contribute to 2 higher order factors: expressive enhancement ability and suppression ability. In Study 1, we also compared the FREE Scale to other commonly used emotion regulation measures, which revealed that suppression ability is conceptually distinct from suppression frequency. In Study 3, we compared the FREE Scale with a composite of traditional frequency-based indices of expressive regulation to predict performance in a previously validated emotional modulation paradigm. Participants' enhancement and suppression ability scores on the FREE Scale predicted their corresponding performance on the laboratory task, even when controlling for baseline expressiveness. These studies suggest that the FREE Scale is a valid and flexible measure of expressive regulation ability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

PubMed

Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

2015-08-01

The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p < 0.001). There was no gender difference in terms of H scores for aromatase expression and double immunohistochemical staining results (p > 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p < 0.001; r = -0.593, p < 0.001; r = -0.650, p < 0.001, respectively). Also, H scores for aromatase co-expression of each hormone were negatively correlated with the H scores for the corresponding hormone (r = -0.503, p < 0.001 for PRL-aromatase and PRL; r = -0.470, p < 0.001 for GH-aromatase, and GH; r = -0.641, p < 0.001 for TSH-aromatase and TSH). H scores for mean aromatase, GH-aromatase, TSH-aromatase were invariant of age (p > 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

PubMed

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

MetaKTSP: a meta-analytic top scoring pair method for robust cross-study validation of omics prediction analysis.

PubMed

Kim, SungHwan; Lin, Chien-Wei; Tseng, George C

2016-07-01

Supervised machine learning is widely applied to transcriptomic data to predict disease diagnosis, prognosis or survival. Robust and interpretable classifiers with high accuracy are usually favored for their clinical and translational potential. The top scoring pair (TSP) algorithm is an example that applies a simple rank-based algorithm to identify rank-altered gene pairs for classifier construction. Although many classification methods perform well in cross-validation of single expression profile, the performance usually greatly reduces in cross-study validation (i.e. the prediction model is established in the training study and applied to an independent test study) for all machine learning methods, including TSP. The failure of cross-study validation has largely diminished the potential translational and clinical values of the models. The purpose of this article is to develop a meta-analytic top scoring pair (MetaKTSP) framework that combines multiple transcriptomic studies and generates a robust prediction model applicable to independent test studies. We proposed two frameworks, by averaging TSP scores or by combining P-values from individual studies, to select the top gene pairs for model construction. We applied the proposed methods in simulated data sets and three large-scale real applications in breast cancer, idiopathic pulmonary fibrosis and pan-cancer methylation. The result showed superior performance of cross-study validation accuracy and biomarker selection for the new meta-analytic framework. In conclusion, combining multiple omics data sets in the public domain increases robustness and accuracy of the classification model that will ultimately improve disease understanding and clinical treatment decisions to benefit patients. An R package MetaKTSP is available online. (http://tsenglab.biostat.pitt.edu/software.htm). ctseng@pitt.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[The value of SYNTAX score in predicting outcome patients undergoing percutaneous coronary intervention].

PubMed

Gao, Yue-chun; Yu, Xian-peng; He, Ji-qiang; Chen, Fang

2012-01-01

To assess the value of SYNTAX score to predict major adverse cardiac and cerebrovascular events (MACCE) among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. 190 patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention (PCI) with Cypher select drug-eluting stent were enrolled. SYNTAX score and clinical SYNTAX score were retrospectively calculated. Our clinical Endpoint focused on MACCE, a composite of death, nonfatal myocardial infarction (MI), stroke and repeat revascularization. The value of SYNTAX score and clinical SYNTAX score to predict MACCE were studied respectively. 29 patients were observed to suffer from MACCE, accounting 18.5% of the overall 190 patients. MACCE rates of low (≤ 20.5), intermediate (21.0 - 31.0), and high (≥ 31.5) tertiles according to SYNTAX score were 9.1%, 16.2% and 30.9% respectively. Both univariate and multivariate analysis showed that SYNTAX score was the independent predictor of MACCE. MACCE rates of low (≤ 19.5), intermediate (19.6 - 29.1), and high (≥ 29.2) tertiles according to clinical SYNTAX score were 14.9%, 9.8% and 30.6% respectively. Both univariate and multivariate analysis showed that clinical SYNTAX score was the independent predictor of MACCE. ROC analysis showed both SYNTAX score (AUC = 0.667, P = 0.004) and clinical SYNTAX score (AUC = 0.636, P = 0.020) had predictive value of MACCE. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score. Both SYNTAX score and clinical SYNTAX score could be independent risk predictors for MACCE among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score in this group of patients.

Genome-wide screen identifies a novel prognostic signature for breast cancer survival

DOE PAGES

Mao, Xuan Y.; Lee, Matthew J.; Zhu, Jeffrey; ...

2017-01-21

Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs. In normal breast tissue, co-expression cliques were identified enriched for cell cycle, gene transcription, cell adhesion,more » cytoskeletal organization and metabolism. In contrast, in BC, only two major co-expression cliques were identified enriched for cell cycle-related processes or blood vessel development, cell adhesion and mammary gland development processes. Interestingly, gene expression levels of 7 genes were found to be negatively correlated with many cell cycle related genes, highlighting these genes as potential tumor suppressors and novel therapeutic targets. A forward-conditional Cox regression analysis was used to identify a 12-gene signature associated with RFS. A prognostic scoring system was created based on the 12-gene signature. This scoring system robustly predicted BC patient RFS in 60 sampling test sets and was further validated in TCGA and METABRIC BC data. Our integrated study identified a 12-gene prognostic signature that could guide adjuvant therapy for BC patients and includes novel potential molecular targets for therapy.« less

Genome-wide screen identifies a novel prognostic signature for breast cancer survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Xuan Y.; Lee, Matthew J.; Zhu, Jeffrey

Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs. In normal breast tissue, co-expression cliques were identified enriched for cell cycle, gene transcription, cell adhesion,more » cytoskeletal organization and metabolism. In contrast, in BC, only two major co-expression cliques were identified enriched for cell cycle-related processes or blood vessel development, cell adhesion and mammary gland development processes. Interestingly, gene expression levels of 7 genes were found to be negatively correlated with many cell cycle related genes, highlighting these genes as potential tumor suppressors and novel therapeutic targets. A forward-conditional Cox regression analysis was used to identify a 12-gene signature associated with RFS. A prognostic scoring system was created based on the 12-gene signature. This scoring system robustly predicted BC patient RFS in 60 sampling test sets and was further validated in TCGA and METABRIC BC data. Our integrated study identified a 12-gene prognostic signature that could guide adjuvant therapy for BC patients and includes novel potential molecular targets for therapy.« less

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

PubMed Central

Wolmark, Norman; Baehner, Frederick L.; Butler, Steven M.; Tang, Gong; Jamshidian, Farid; Sing, Amy P.; Shak, Steven; Paik, Soonmyung

2016-01-01

Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. PMID:27217450

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.

PubMed

Wolmark, Norman; Mamounas, Eleftherios P; Baehner, Frederick L; Butler, Steven M; Tang, Gong; Jamshidian, Farid; Sing, Amy P; Shak, Steven; Paik, Soonmyung

2016-07-10

We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. © 2016 by American Society of Clinical Oncology.

Japanese scoring systems to predict resistance to intravenous immunoglobulin in Kawasaki disease were unreliable for Caucasian Israeli children.

PubMed

Arane, Karen; Mendelsohn, Kerry; Mimouni, Michael; Mimouni, Francis; Koren, Yael; Simon, Dafna Brik; Bahat, Hilla; Helou, Mona Hanna; Mendelson, Amir; Hezkelo, Nofar; Glatstein, Miguel; Berkun, Yackov; Eisenstein, Eli; Aviel, Yonatan Butbul; Brik, Riva; Hashkes, Philip J; Uziel, Yosef; Harel, Liora; Amarilyo, Gil

2018-05-24

This study assessed the validity of using established Japanese risk scoring methods to predict intravenous immunoglobulin (IVIG) resistance to Kawasaki disease in Israeli children. We reviewed the medical records of 282 patients (70% male) with Kawasaki disease from six Israeli medical centres between 2004-2013. Their mean age was 2.5 years. The risk scores were calculated using the Kobayashi, Sano and Egami scoring methods and analysed to determine if a higher risk score predicted IVIG resistance in this population. Factors that predicted a lack of response to the initial IVIG dose were identified. We found that 18% did not respond to the first IVIG dose. The three scoring methods were unable to reliably predict IVIG resistance, with sensitivities of 23-32% and specificities of 67-87%. Calculating a predictive score that was specific for this population was also unsuccessful. The factors that predicted a lacked of response to the first IVIG dose included low albumin, elevated total bilirubin and ethnicity. The established risk scoring methods created for Japanese populations with Kawasaki disease were not suitable for predicting IVIG resistance in Caucasian Israeli children and we were unable to create a specific scoring method that was able to do this. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy.

PubMed

Elhady, Marwa; Youness, Eman R; Gafar, Heba S; Abdel Aziz, Ali; Mostafa, Rehab S I

2018-06-02

Irisin and chemerin peptides expression are triggered by hypoxia and involved in activation of inflammatory cascades in various organs including the brain; however, their role in epilepsy is not fully illustrated. This study aims to explore the predictive role of irisin and chemerin for seizure control in children with idiopathic epilepsy. This cross-sectional comparative study included 50 children with idiopathic epilepsy; 25 of them had controlled seizures over the previous 6 months and 30 age- and sex-matched healthy children as controls. Epilepsy characteristics, seizure severity Chalfont score, and response to medications were assessed in relation to serum irisin and chemerin levels. In comparison to healthy controls, serum chemerin and irisin levels were significantly higher in children with idiopathic epilepsy especially those with uncontrolled seizures. Serum chemerin and irisin levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. Elevated Chalfont score (OR 3.19), serum chemerin (OR 2.01), and irisin (OR 2.03) are predictors of uncontrolled seizures. Circulating chemerin and irisin have 80% and 76% sensitivity and 88% and 92% specificity at cutoff point > 191.38 ng/ml and > 151.2 ng/ml respectively for prediction of uncontrolled seizures in children with idiopathic epilepsy. Elevated circulating level of irisin and chemerin may predict poor seizure control in children with idiopathic epilepsy suggesting the role of hypoxia-triggered neuroinflammation in the pathogenesis of childhood idiopathic epilepsy.

A score for the differential diagnosis of bradykinin- and histamine-induced head and neck swellings.

PubMed

Lenschow, M; Bas, M; Johnson, F; Wirth, M; Strassen, U

2018-05-02

Acute edema of the head and neck region may lead to life-threatening dyspnea and require quick and targeted treatment. They can be subdivided in bradykinin- and histamine-mediated swellings, which require treatment with different classes of pharmaceuticals. Clinical pathways for differential diagnoses do not exist so far, although it is known that early treatment is decisive for faster symptom relief and reduced expression of the swellings. Aim of the study was the creation of a clinical algorithm for identification of bradykinin-mediated angioedema. 188 patients that presented to our outpatient department between 2010 and 2016 with an acute, non-inflammatory swelling of the head and neck region were included in our retrospective study. All available anamnestic and clinical parameters were obtained from patient files. Parameters showing significant differences between the two groups were included in our score. Utilization of the Youden's index allowed determination of an optimal cut-off value. 76 patients could be assigned to the histamine and 112 patients to bradykinin group. The following parameters were included in our score: age, dyspnea, itching or erythema, glucocorticoid response and intake of ACEi/AT-II blockers. The cut-off value is set at three points. The proposed score yielded a sensitivity for identification of bradykinin-mediated angioedema of 96%, a specificity of 84%, a positive predictive value of 91% and a negative predictive value of 93%. Utilization of the proposed score allows quick and reliable assignment of patients to the correct subgroup and thereby reduces time for treatment.

Dual expression of MYC and BCL2 proteins predicts worse outcomes in diffuse large B-cell lymphoma.

PubMed

Clark Schneider, Kelli M; Banks, Peter M; Collie, Angela M B; Lanigan, Christopher P; Manilich, Elena; Durkin, Lisa M; Hill, Brian T; Hsi, Eric D

2016-07-01

Recent studies suggested that MYC and BCL2 protein co-expression is an independent indicator of poor prognosis in diffuse large B-cell lymphoma. However, the immunohistochemistry protocols for dual-expression staining and the scoring cut-offs vary by study. Sixty-nine cases of diffuse large B-cell lymphoma were evaluated for MYC and BCL2 protein expression using various cut-offs that have been recommended in prior studies. Independent of the International Prognostic Index risk group, cases with dual protein expression of BCL2 and MYC using ≥50%/40% cut-offs and ≥70%/40% had significantly shorter overall survival than cases without. It was verified in this patient population that the use of BCL2 and MYC immunohistochemistry, performed with available in vitro diagnostic-cleared antibodies, provides rapid prognostic information in patients with de novo diffuse large B-cell lymphoma. This study has practical implications for diagnostic laboratories and serves as a guide for implementation in the setting of future clinical trials.

Validation of prognostic scores for clinical outcomes in cirrhotic patients with acute variceal bleeding.

PubMed

Motola-Kuba, Miguel; Escobedo-Arzate, Angélica; Tellez-Avila, Félix; Altamirano, José; Aguilar-Olivos, Nancy; González-Angulo, Alberto; Zamarripa-Dorsey, Felipe; Uribe, Misael; Chávez-Tapia, Norberto C

Background. The Rockall, Glasgow-Blatchford, and AIMS65 are useful and validated scoring systems for predicting the outcomes of patients with nonvariceal gastrointestinal bleeding. However, there are no validated evidence for using them to predict outcomes on variceal bleeding. The aim of this study was to evaluate and compare the prognostic accuracy of different nonvariceal bleeding scores with other liver-specific scoring systems in cirrhotic patients. A retrospective multicenter study that included 160 cirrhotic patients with acute variceal bleeding. The AUROC's to predict in-hospital mortality, and rebleeding, were analyzed for each scoring system. Overall in-hospital mortality occurred in 13% and in-hospital rebleeding in 12% of patients. The systems with the best AUROC value for predicting mortality were MELD (0.828; 95% CI 0.748-0.909), and AIMS65 (0.817; 95% CI 0.724-0.909). The best score systems for predicting rebleeding were Glasgow-Blatchford (0.756; 95% CI 0.640- 0.827), and Rockall (0.691; 95% CI 0.580-0.802). In addition to liver-specific scores, the AIMS65 score is accurate for predicting in-hospital mortality in cirrhotic patients with acute variceal bleeding. Other scoring systems might be useful for predicting significant clinical outcomes in these patients.

A community computational challenge to predict the activity of pairs of compounds.

PubMed

Bansal, Mukesh; Yang, Jichen; Karan, Charles; Menden, Michael P; Costello, James C; Tang, Hao; Xiao, Guanghua; Li, Yajuan; Allen, Jeffrey; Zhong, Rui; Chen, Beibei; Kim, Minsoo; Wang, Tao; Heiser, Laura M; Realubit, Ronald; Mattioli, Michela; Alvarez, Mariano J; Shen, Yao; Gallahan, Daniel; Singer, Dinah; Saez-Rodriguez, Julio; Xie, Yang; Stolovitzky, Gustavo; Califano, Andrea

2014-12-01

Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing. We highlight similarities between the methods. Although the accuracy of predictions was not optimal, we find that computational prediction of compound-pair activity is possible, and that community challenges can be useful to advance the field of in silico compound-synergy prediction.

Discovering mutated driver genes through a robust and sparse co-regularized matrix factorization framework with prior information from mRNA expression patterns and interaction network.

PubMed

Xi, Jianing; Wang, Minghui; Li, Ao

2018-06-05

Discovery of mutated driver genes is one of the primary objective for studying tumorigenesis. To discover some relatively low frequently mutated driver genes from somatic mutation data, many existing methods incorporate interaction network as prior information. However, the prior information of mRNA expression patterns are not exploited by these existing network-based methods, which is also proven to be highly informative of cancer progressions. To incorporate prior information from both interaction network and mRNA expressions, we propose a robust and sparse co-regularized nonnegative matrix factorization to discover driver genes from mutation data. Furthermore, our framework also conducts Frobenius norm regularization to overcome overfitting issue. Sparsity-inducing penalty is employed to obtain sparse scores in gene representations, of which the top scored genes are selected as driver candidates. Evaluation experiments by known benchmarking genes indicate that the performance of our method benefits from the two type of prior information. Our method also outperforms the existing network-based methods, and detect some driver genes that are not predicted by the competing methods. In summary, our proposed method can improve the performance of driver gene discovery by effectively incorporating prior information from interaction network and mRNA expression patterns into a robust and sparse co-regularized matrix factorization framework.

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Inferring dynamic gene regulatory networks in cardiac differentiation through the integration of multi-dimensional data.

PubMed

Gong, Wuming; Koyano-Nakagawa, Naoko; Li, Tongbin; Garry, Daniel J

2015-03-07

Decoding the temporal control of gene expression patterns is key to the understanding of the complex mechanisms that govern developmental decisions during heart development. High-throughput methods have been employed to systematically study the dynamic and coordinated nature of cardiac differentiation at the global level with multiple dimensions. Therefore, there is a pressing need to develop a systems approach to integrate these data from individual studies and infer the dynamic regulatory networks in an unbiased fashion. We developed a two-step strategy to integrate data from (1) temporal RNA-seq, (2) temporal histone modification ChIP-seq, (3) transcription factor (TF) ChIP-seq and (4) gene perturbation experiments to reconstruct the dynamic network during heart development. First, we trained a logistic regression model to predict the probability (LR score) of any base being bound by 543 TFs with known positional weight matrices. Second, four dimensions of data were combined using a time-varying dynamic Bayesian network model to infer the dynamic networks at four developmental stages in the mouse [mouse embryonic stem cells (ESCs), mesoderm (MES), cardiac progenitors (CP) and cardiomyocytes (CM)]. Our method not only infers the time-varying networks between different stages of heart development, but it also identifies the TF binding sites associated with promoter or enhancers of downstream genes. The LR scores of experimentally verified ESCs and heart enhancers were significantly higher than random regions (p <10(-100)), suggesting that a high LR score is a reliable indicator for functional TF binding sites. Our network inference model identified a region with an elevated LR score approximately -9400 bp upstream of the transcriptional start site of Nkx2-5, which overlapped with a previously reported enhancer region (-9435 to -8922 bp). TFs such as Tead1, Gata4, Msx2, and Tgif1 were predicted to bind to this region and participate in the regulation of Nkx2-5 gene expression. Our model also predicted the key regulatory networks for the ESC-MES, MES-CP and CP-CM transitions. We report a novel method to systematically integrate multi-dimensional -omics data and reconstruct the gene regulatory networks. This method will allow one to rapidly determine the cis-modules that regulate key genes during cardiac differentiation.

Limitations of expressing left ventricular mass relative to height and to body surface area in children.

PubMed

Foster, Bethany J; Gao, Tao; Mackie, Andrew S; Zemel, Babette S; Ali, Huma; Platt, Robert W; Colan, Steven D

2013-04-01

Left ventricular (LV) mass varies in proportion to lean body mass (LBM) but is usually expressed relative to height or body surface area (BSA), each of which functions as a surrogate for LBM. The aims of this study were to characterize the adiposity-related biases associated with each of these scaling variables and to determine the impact of these biases on the diagnosis of LV hypertrophy (LVH) in a group of children at risk for LVH. In a retrospective study, LV mass was estimated using M-mode echocardiography in 222 healthy nonoverweight reference children and 112 children "at risk" for LVH (48 healthy overweight children and 64 children with hypertension). LBM was estimated for all children using validated predictive equations and was considered the criterion scaling variable. Z scores for LV mass for LBM, LV mass for height, and LV mass for BSA were calculated for each child relative to the reference group. The performance of height-based and BSA-based Z scores were compared with that of LBM-based Z scores at different levels of adiposity (estimated by the Z score for body mass index for age [BMIz]). Among healthy normotensive children, LV mass-for-height Z scores were greater than LV mass-for-LBM Z scores at higher values of BMIz and lower than LV mass-for-LBM Z scores at lower values of BMIz (R(2) = 0.52, P < .0001). LV mass-for-BSA Z scores for agreed well with LBM-based Z scores at BMIz < 0.7 but were lower than LV mass-for-LBM Z scores for at BMIz > 0.7 (R(2) = 0.31, P < .0001). Compared with 13% of at-risk children classified as having LVH on the basis of LV mass for LBM > 95th percentile, 30% and 11% had LVH when LV mass was scaled to height and BSA, respectively. Scaling LV mass to BSA in children results in less misclassification with respect to LVH than does scaling to height. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

MetaMQAP: a meta-server for the quality assessment of protein models.

PubMed

Pawlowski, Marcin; Gajda, Michal J; Matlak, Ryszard; Bujnicki, Janusz M

2008-09-29

Computational models of protein structure are usually inaccurate and exhibit significant deviations from the true structure. The utility of models depends on the degree of these deviations. A number of predictive methods have been developed to discriminate between the globally incorrect and approximately correct models. However, only a few methods predict correctness of different parts of computational models. Several Model Quality Assessment Programs (MQAPs) have been developed to detect local inaccuracies in unrefined crystallographic models, but it is not known if they are useful for computational models, which usually exhibit different and much more severe errors. The ability to identify local errors in models was tested for eight MQAPs: VERIFY3D, PROSA, BALA, ANOLEA, PROVE, TUNE, REFINER, PROQRES on 8251 models from the CASP-5 and CASP-6 experiments, by calculating the Spearman's rank correlation coefficients between per-residue scores of these methods and local deviations between C-alpha atoms in the models vs. experimental structures. As a reference, we calculated the value of correlation between the local deviations and trivial features that can be calculated for each residue directly from the models, i.e. solvent accessibility, depth in the structure, and the number of local and non-local neighbours. We found that absolute correlations of scores returned by the MQAPs and local deviations were poor for all methods. In addition, scores of PROQRES and several other MQAPs strongly correlate with 'trivial' features. Therefore, we developed MetaMQAP, a meta-predictor based on a multivariate regression model, which uses scores of the above-mentioned methods, but in which trivial parameters are controlled. MetaMQAP predicts the absolute deviation (in Angströms) of individual C-alpha atoms between the model and the unknown true structure as well as global deviations (expressed as root mean square deviation and GDT_TS scores). Local model accuracy predicted by MetaMQAP shows an impressive correlation coefficient of 0.7 with true deviations from native structures, a significant improvement over all constituent primary MQAP scores. The global MetaMQAP score is correlated with model GDT_TS on the level of 0.89. Finally, we compared our method with the MQAPs that scored best in the 7th edition of CASP, using CASP7 server models (not included in the MetaMQAP training set) as the test data. In our benchmark, MetaMQAP is outperformed only by PCONS6 and method QA_556 - methods that require comparison of multiple alternative models and score each of them depending on its similarity to other models. MetaMQAP is however the best among methods capable of evaluating just single models. We implemented the MetaMQAP as a web server available for free use by all academic users at the URL https://genesilico.pl/toolkit/

Novel pre-therapeutic scoring system using patient and haematological data to predict facial palsy prognosis.

PubMed

Wasano, K; Ishikawa, T; Kawasaki, T; Yamamoto, S; Tomisato, S; Shinden, S; Minami, S; Wakabayashi, T; Ogawa, K

2017-12-01

We describe a novel scoring system, the facial Palsy Prognosis Prediction score (PPP score), which we test for reliability in predicting pre-therapeutic prognosis of facial palsy. We aimed to use readily available patient data that all clinicians have access to before starting treatment. Multicenter case series with chart review. Three tertiary care hospitals. We obtained haematological and demographic data from 468 facial palsy patients who were treated between 2010 and 2014 in three tertiary care hospitals. Patients were categorised as having Bell's palsy or Ramsey Hunt's palsy. We compared the data of recovered and unrecovered patients. PPP scores consisted of combinatorial threshold values of continuous patient data (eg platelet count) and categorical variables (eg gender) that best predicted recovery. We created separate PPP scores for Bell's palsy patients (PPP-B) and for Ramsey Hunt's palsy patients (PPP-H). The PPP-B score included age (≥65 years), gender (male) and neutrophil-to-lymphocyte ratio (≥2.9). The PPP-H score included age (≥50 years), monocyte rate (≥6.0%), mean corpuscular volume (≥95 fl) and platelet count (≤200 000 /μL). Patient recovery rate significantly decreased with increasing PPP scores (both PPP-B and PPP-H) in a step-wise manner. PPP scores (ie PPP-B score and PPP-H score) ≥2 were associated with worse than average prognosis. Palsy Prognosis Prediction scores are useful for predicting prognosis of facial palsy before beginning treatment. © 2017 John Wiley & Sons Ltd.

Difficulties Using Standardized Tests to Identify the Receptive Expressive Gap in Bilingual Children's Vocabularies.

PubMed

Gibson, Todd A; Oller, D Kimbrough; Jarmulowicz, Linda

2018-03-01

Receptive standardized vocabulary scores have been found to be much higher than expressive standardized vocabulary scores in children with Spanish as L1, learning L2 (English) in school (Gibson et al., 2012). Here we present evidence suggesting the receptive-expressive gap may be harder to evaluate than previously thought because widely-used standardized tests may not offer comparable normed scores. Furthermore monolingual Spanish-speaking children tested in Mexico and monolingual English-speaking children in the US showed other, yet different statistically significant discrepancies between receptive and expressive scores. Results suggest comparisons across widely used standardized tests in attempts to assess a receptive-expressive gap are precarious.

Comparison of mortality prediction models in burns ICU patients in Pinderfields Hospital over 3 years.

PubMed

Douglas, Helen E; Ratcliffe, Andrew; Sandhu, Rajdeep; Anwar, Umair

2015-02-01

Many different burns mortality prediction models exist; however most agree that important factors that can be weighted include the age of the patient, the total percentage of body surface area burned and the presence or absence of smoke inhalation. A retrospective review of all burns primarily admitted to Pinderfields Burns ICU under joint care of burns surgeons and intensivists for the past 3 years was completed. Predicted mortality was calculated using the revised Baux score (2010), the Belgian Outcome in Burn Injury score (2009) and the Boston group score by Ryan et al. (1998). Additionally 28 of the 48 patients had APACHE II scores recorded on admission and the predicted and actual mortality of this group were compared. The Belgian score had the highest sensitivity and negative predictive value (72%/85%); followed by the Boston score (66%/78%) and then the revised Baux score (53%/70%). APACHE II scores had higher sensitivity (81%) and NPV (92%) than any of the burns scores. In our group of burns ICU patients the Belgian model was the most sensitive and specific predictor of mortality. In our subgroup of patients with APACHE II data, this score more accurately predicted survival and mortality. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Comparison of three scoring systems for risk stratification in elderly patients wıth acute upper gastrointestinal bleeding.

PubMed

Kalkan, Çağdaş; Soykan, Irfan; Karakaya, Fatih; Tüzün, Ali; Gençtürk, Zeynep Bıyıklı

2017-04-01

Acute gastrointestinal bleeding is a potentially life-threatening condition that requires rapid assessment and dynamic management. Several scoring systems are used to predict mortality and rebleeding in such cases. The aim of the present study was to compare three scoring systems for predicting short-term mortality, rebleeding, duration of hospitalization and the need for blood transfusion in elderly patients with upper gastrointestinal bleeding. The present study included 335 elderly patients with upper gastrointestinal bleeding. Pre- and post-endoscopic Rockall, Glasgow-Blatchford and AIMS65 scores were calculated. The ability of these scores to predict rebleeding, mortality, duration of hospitalization and the need for blood transfusion was determined. Pre- (4.5) and post-endoscopic (7.5) Rockall scores were superior to the Glasgow-Blatchford (12.5) score for predicting mortality (P = 0.006 and P = 0.015). Likewise, pre- (4.5) and post-endoscopic Rockall scores were superior to the respective Glasgow-Blatchford scores for predicting rebleeding (P = 0.013 and P = 0.03). There was an association between duration of hospitalization and mortality; as the duration of hospitalization increased the mortality rate increased. In all, 94% of patients hospitalized for a mean of 5 days were alive versus 56.1% of those hospitalized for 20 days, and 20.2% of those hospitalized for 40 days. In elderly patients with upper gastrointestinal bleeding, the Rockall score is clinically more useful for predicting mortality and rebleeding than the Glasgow-Blatchford and AIMS65 scores; however, for predicting duration of hospitalization and the need for blood transfusion, the Glasgow-Blatchford score is superior to the Rockall and AIMS65 scores. Geriatr Gerontol Int 2017; 17: 575-583. © 2016 Japan Geriatrics Society.

Changes in plasma thrombospondin-1 concentrations following acute intracerebral hemorrhage.

PubMed

Dong, Xiao-Qiao; Yu, Wen-Hua; Zhu, Qiang; Cheng, Zhen-Yu; Chen, Yi-Hua; Lin, Xiao-Feng; Ten, Xian-Lin; Tang, Xiao-Bing; Chen, Juan

2015-10-23

Angiogenesis is a fundamental process for brain development and repair. Thrombospondin-1 is the first identified endogenous angiogenesis inhibitor. Its expression in rat brain is upregulated after intracerebral hemorrhage (ICH). We determined whether plasma thrombospondin-1 concentrations are associated with injury severity and prognosis in ICH patients. This observational, prospective study recruited 110 patients and 110 age- and gender-matched healthy controls. Blood samples were collected from the patients at admission and from the healthy controls at study entry to measure plasma thrombospondin-1 concentrations. The endpoints included 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome (modified Rankin Scale score >2). Plasma thrombospondin-1 concentrations were markedly higher in patients than in healthy controls. Thrombospondin-1 was an independent predictive factor for all endpoints and plasma thrombospondin-1 concentrations were highly associated with injury severity reflected by hematoma volume and National Institutes of Health Stroke Scale score. Under receiver operating characteristic curves, plasma thrombospondin-1 concentrations had similar predictive values compared with hematoma volume and National Institutes of Health Stroke Scale score. Increased plasma thrombospondin-1 concentrations following ICH are independently associated with injury severity and short-term and long-term clinical outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Zero-Time Renal Transplant Biopsies: A Comprehensive Review.

PubMed

Naesens, Maarten

2016-07-01

Zero-time kidney biopsies, obtained at time of transplantation, are performed in many transplant centers worldwide. Decisions on kidney discard, kidney allocation, and choice of peritransplant and posttransplant treatment are sometimes based on the histological information obtained from these biopsies. This comprehensive review evaluates the practical considerations of performing zero-time biopsies, the predictive performance of zero-time histology and composite histological scores, and the clinical utility of these biopsies. The predictive performance of individual histological lesions and of composite scores for posttransplant outcome is at best moderate. No single histological lesion or composite score is sufficiently robust to be included in algorithms for kidney discard. Dual kidney transplantation has been based on histological assessment of zero-time biopsies and improves outcome in individual patients, but the waitlist effects of this strategy remain obscure. Zero-time biopsies are valuable for clinical and translational research purposes, providing insight in risk factors for posttransplant events, and as baseline for comparison with posttransplant histology. The molecular phenotype of zero-time biopsies yields novel therapeutic targets for improvement of donor selection, peritransplant management and kidney preservation. It remains however highly unclear whether the molecular expression variation in zero-time biopsies could become a better predictor for posttransplant outcome than donor/recipient baseline demographic factors.

Automated Cognitive Health Assessment From Smart Home-Based Behavior Data.

PubMed

Dawadi, Prafulla Nath; Cook, Diane Joyce; Schmitter-Edgecombe, Maureen

2016-07-01

Smart home technologies offer potential benefits for assisting clinicians by automating health monitoring and well-being assessment. In this paper, we examine the actual benefits of smart home-based analysis by monitoring daily behavior in the home and predicting clinical scores of the residents. To accomplish this goal, we propose a clinical assessment using activity behavior (CAAB) approach to model a smart home resident's daily behavior and predict the corresponding clinical scores. CAAB uses statistical features that describe characteristics of a resident's daily activity performance to train machine learning algorithms that predict the clinical scores. We evaluate the performance of CAAB utilizing smart home sensor data collected from 18 smart homes over two years. We obtain a statistically significant correlation ( r=0.72) between CAAB-predicted and clinician-provided cognitive scores and a statistically significant correlation ( r=0.45) between CAAB-predicted and clinician-provided mobility scores. These prediction results suggest that it is feasible to predict clinical scores using smart home sensor data and learning-based data analysis.

Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.

PubMed

Mina, Lida; Soule, Sharon E; Badve, Sunil; Baehner, Fredrick L; Baker, Joffre; Cronin, Maureen; Watson, Drew; Liu, Mei-Lan; Sledge, George W; Shak, Steve; Miller, Kathy D

2007-06-01

Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

Predictive power of the DASA-IV: Variations in rating method and timescales.

PubMed

Nqwaku, Mphindisi; Draycott, Simon; Aldridge-Waddon, Luke; Bush, Emma-Louise; Tsirimokou, Alexandra; Jones, Dominic; Puzzo, Ignazio

2018-05-10

This project evaluated the predictive validity of the Dynamic Appraisal of Situational Aggression - Inpatient Version (DASA-IV) in a high-secure psychiatric hospital in the UK over 24 hours and over a single nursing shift. DASA-IV scores from three sequential nursing shifts over a 24-hour period were compared with the mean (average of three scores across the 24-hour period) and peak (highest of the three scores across the 24-hour period) scores across these shifts. In addition, scores from a single nursing shift were used to predict aggressive incidents over each of the following three shifts. The DASA-IV was completed by nursing staff during handover meetings, rating 43 male psychiatric inpatients over a period of 6 months. Data were compared to incident reports recorded over the same period. Receiver operating characteristic (ROC) curves and generalized estimating equations assessed the predictive ability of various DASA-IV scores over 24-hour and single-shift timescales. Scores from the DASA-IV based on a single shift had moderate predictive ability for aggressive incidents occurring the next calendar day, whereas scores based on all three shifts had excellent predictive ability. DASA-IV scores from a single shift showed moderate predictive ability for each of the following three shifts. The DASA-IV has excellent predictive ability for aggressive incidents within a secure setting when data are summarized over a 24-hour period, as opposed to when a single rating is taken. In addition, it has moderate value for predicting incidents over even shorter timescales. © 2018 Australian College of Mental Health Nurses Inc.

Does IQ influence associations between ADHD symptoms and other cognitive functions in young preschoolers?

PubMed

Rohrer-Baumgartner, Nina; Zeiner, Pål; Egeland, Jens; Gustavson, Kristin; Skogan, Annette Holth; Reichborn-Kjennerud, Ted; Aase, Heidi

2014-05-01

Working memory, inhibition, and expressive language are often impaired in ADHD and many children with ADHD have lower IQ-scores than typically developing children. The aim of this study was to test whether IQ-score influences associations between ADHD symptoms and verbal and nonverbal working memory, inhibition, and expressive language, respectively, in a nonclinical sample of preschool children. In all, 1181 children recruited from the Norwegian Mother and Child Cohort Study were clinically assessed at the age of 36 to 46 months. IQ-score and working memory were assessed with subtasks from the Stanford Binet test battery, expressive language was reported by preschool teachers (Child Development Inventory), response inhibition was assessed with a subtask from the NEPSY test, and ADHD symptoms were assessed by parent interview (Preschool Age Psychiatric Assessment). The results showed an interaction between ADHD symptoms and IQ-score on teacher-reported expressive language. In children with below median IQ-score, a larger number of ADHD symptoms were more likely to be accompanied by reports of lower expressive language skills, while the level of ADHD symptoms exerted a smaller effect on reported language skills in children with above median IQ-score. The associations between ADHD symptoms and working memory and response inhibition, respectively, were not influenced by IQ-score. Level of IQ-score affected the relation between ADHD symptoms and teacher-reported expressive language, whereas associations between ADHD symptoms and working memory and response inhibition, respectively, were significant and of similar sizes regardless of IQ-score. Thus, in preschoolers, working memory and response inhibition should be considered during an ADHD assessment regardless of IQ-score, while language skills of young children are especially important to consider when IQ-scores are average or low.

Does IQ influence Associations between ADHD Symptoms and other Cognitive Functions in young Preschoolers?

PubMed Central

2014-01-01

Background Working memory, inhibition, and expressive language are often impaired in ADHD and many children with ADHD have lower IQ-scores than typically developing children. The aim of this study was to test whether IQ-score influences associations between ADHD symptoms and verbal and nonverbal working memory, inhibition, and expressive language, respectively, in a nonclinical sample of preschool children. Methods In all, 1181 children recruited from the Norwegian Mother and Child Cohort Study were clinically assessed at the age of 36 to 46 months. IQ-score and working memory were assessed with subtasks from the Stanford Binet test battery, expressive language was reported by preschool teachers (Child Development Inventory), response inhibition was assessed with a subtask from the NEPSY test, and ADHD symptoms were assessed by parent interview (Preschool Age Psychiatric Assessment). Results The results showed an interaction between ADHD symptoms and IQ-score on teacher-reported expressive language. In children with below median IQ-score, a larger number of ADHD symptoms were more likely to be accompanied by reports of lower expressive language skills, while the level of ADHD symptoms exerted a smaller effect on reported language skills in children with above median IQ-score. The associations between ADHD symptoms and working memory and response inhibition, respectively, were not influenced by IQ-score. Conclusions Level of IQ-score affected the relation between ADHD symptoms and teacher-reported expressive language, whereas associations between ADHD symptoms and working memory and response inhibition, respectively, were significant and of similar sizes regardless of IQ-score. Thus, in preschoolers, working memory and response inhibition should be considered during an ADHD assessment regardless of IQ-score, while language skills of young children are especially important to consider when IQ-scores are average or low. PMID:24884579

Scoring systems for outcome prediction in patients with perforated peptic ulcer

PubMed Central

2013-01-01

Background Patients with perforated peptic ulcer (PPU) often present with acute, severe illness that carries a high risk for morbidity and mortality. Mortality ranges from 3-40% and several prognostic scoring systems have been suggested. The aim of this study was to review the available scoring systems for PPU patients, and to assert if there is evidence to prefer one to the other. Material and methods We searched PubMed for the mesh terms “perforated peptic ulcer”, “scoring systems”, “risk factors”, ”outcome prediction”, “mortality”, ”morbidity” and the combinations of these terms. In addition to relevant scores introduced in the past (e.g. Boey score), we included recent studies published between January 2000 and December 2012) that reported on scoring systems for prediction of morbidity and mortality in PPU patients. Results A total of ten different scoring systems used to predict outcome in PPU patients were identified; the Boey score, the Hacettepe score, the Jabalpur score the peptic ulcer perforation (PULP) score, the ASA score, the Charlson comorbidity index, the sepsis score, the Mannheim Peritonitis Index (MPI), the Acute physiology and chronic health evaluation II (APACHE II), the simplified acute physiology score II (SAPS II), the Mortality probability models II (MPM II), the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity physical sub-score (POSSUM-phys score). Only four of the scores were specifically constructed for PPU patients. In five studies the accuracy of outcome prediction of different scoring systems was evaluated by receiver operating characteristics curve (ROC) analysis, and the corresponding area under the curve (AUC) among studies compared. Considerable variation in performance both between different scores and between different studies was found, with the lowest and highest AUC reported between 0.63 and 0.98, respectively. Conclusion While the Boey score and the ASA score are most commonly used to predict outcome for PPU patients, considerable variations in accuracy for outcome prediction were shown. Other scoring systems are hampered by a lack of validation or by their complexity that precludes routine clinical use. While the PULP score seems promising it needs external validation before widespread use. PMID:23574922

Predicting preference-based SF-6D index scores from the SF-8 health survey.

PubMed

Wang, P; Fu, A Z; Wee, H L; Lee, J; Tai, E S; Thumboo, J; Luo, N

2013-09-01

To develop and test functions for predicting the preference-based SF-6D index scores from the SF-8 health survey. This study was a secondary analysis of data collected in a population health survey in which respondents (n = 7,529) completed both the SF-36 and the SF-8 questionnaires. We examined seven ordinary least-square estimators for their performance in predicting SF-6D scores from the SF-8 at both the individual and the group levels. In general, all functions performed similarly well in predicting SF-6D scores, and the predictions at the group level were better than predictions at the individual level. At the individual level, 42.5-51.5% of prediction errors were smaller than the minimally important difference (MID) of the SF-6D scores, depending on the function specifications, while almost all prediction errors of the tested functions were smaller than the MID of SF-6D at the group level. At both individual and group levels, the tested functions predicted lower than actual scores at the higher end of the SF-6D scale. Our study developed functions to generate preference-based SF-6D index scores from the SF-8 health survey, the first of its kind. Further research is needed to evaluate the performance and validity of the prediction functions.

Perspective taking in children's narratives about jealousy.

PubMed

Aldrich, Naomi J; Tenenbaum, Harriet R; Brooks, Patricia J; Harrison, Karine; Sines, Jennie

2011-03-01

This study explored relationships between perspective-taking, emotion understanding, and children's narrative abilities. Younger (23 5-/6-year-olds) and older (24 7-/8-year-olds) children generated fictional narratives, using a wordless picture book, about a frog experiencing jealousy. Children's emotion understanding was assessed through a standardized test of emotion comprehension and their ability to convey the jealousy theme of the story. Perspective-taking ability was assessed with respect to children's use of narrative evaluation (i.e., narrative coherence, mental state language, supplementary evaluative speech, use of subjective language, and placement of emotion expression). Older children scored higher than younger children on emotion comprehension and on understanding the story's complex emotional theme, including the ability to identify a rival. They were more advanced in perspective-taking abilities, and selectively used emotion expressions to highlight story episodes. Subjective perspective taking and narrative coherence were predictive of children's elaboration of the jealousy theme. Use of supplementary evaluative speech, in turn, was predictive of both subjective perspective taking and narrative coherence. ©2010 The British Psychological Society.

Children's understanding of ambiguous idioms and conversational perspective-taking.

PubMed

Le Sourn-Bissaoui, Sandrine; Caillies, Stéphanie; Bernard, Stéphane; Deleau, Michel; Brulé, Lauriane

2012-08-01

The aim of this study was to test the hypothesis that conversational perspective-taking is a determinant of unfamiliar ambiguous idiom comprehension. We investigated two types of ambiguous idiom, decomposable and nondecomposable expressions, which differ in the degree to which the literal meanings of the individual words contribute to the overall idiomatic meaning. We designed an experiment to assess the relationship between the acquisition of figurative comprehension and conversational perspective-taking. Our sample of children aged 5-7 years performed three conversational perspective-taking tasks (language acts, shared/unshared information, and conversational maxims). They then listened to decomposable and nondecomposable idiomatic expressions presented in context before performing a multiple-choice task (figurative, literal, and contextual responses). Results indicated that decomposable idiom comprehension was predicted by conversational perspective-taking scores and language skills, whereas nondecomposable idiom comprehension was predicted solely by language skills. We discuss our findings with respect to verbal and pragmatic skills. Copyright © 2012 Elsevier Inc. All rights reserved.

The relationship between psychosocial maturity and assertiveness in males and females.

PubMed

Goldman, J A; Olczak, P V

1981-02-01

The relationship between psychosocial maturity (psychological health) and assertiveness was investigated in a sample of United States college males and females. Results revealed a moderately high positive relationship between psychosocial maturity (PSM) and self-reported assertiveness on the Rathus and Galassi scales for both sexes. This relationship was slightly stronger (in terms of variance accounted for) for males than females, significant differences being obtained for Intimacy on the Rathus scale and PSM and Intimacy on the Galassi scale. Multiple regression analyses revealed that the personality components most consistently accounting for major portions of the variance in predicting male assertiveness scores on both the Rathus Assertiveness Schedule and the College Self-Expression Scale were Intimacy and Initiative, while in predicting female assertiveness, only Initiative was involved. The findings were related to previous research, recent work on the androgyny construct (instrumental vs. expressive behaviors), and exhortations for increased cooperation between schools of psychotherapy to establish it as a more unified discipline.

Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.

PubMed

Saraon, Punit; Trudel, Dominique; Kron, Ken; Dmitromanolakis, Apostolos; Trachtenberg, John; Bapat, Bharati; van der Kwast, Theodorus; Jarvi, Keith A; Diamandis, Eleftherios P

2014-04-01

Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. © 2013 Wiley Periodicals, Inc.

Predictive value of CHADS2 and CHA2DS2-VASc scores for acute myocardial infarction in patients with atrial fibrillation.

PubMed

Pang, Hui; Han, Bing; Fu, Qiang; Zong, Zhenkun

2017-07-05

The presence of acute myocardial infarction (AMI) confers a poor prognosis in atrial fibrillation (AF), associated with increased mortality dramatically. This study aimed to evaluate the predictive value of CHADS 2 and CHA 2 DS 2 -VASc scores for AMI in patients with AF. This retrospective study enrolled 5140 consecutive nonvalvular AF patients, 300 patients with AMI and 4840 patients without AMI. We identified the optimal cut-off values of the CHADS 2 and CHA 2 DS 2 -VASc scores each based on receiver operating characteristic curves to predict the risk of AMI. Both CHADS 2 score and CHA 2 DS 2 -VASc score were associated with an increased odds ratio of the prevalence of AMI in patients with AF, after adjustment for hyperlipidaemia, hyperuricemia, hyperthyroidism, hypothyroidism and obstructive sleep apnea. The present results showed that the area under the curve (AUC) for CHADS 2 score was 0.787 with a similar accuracy of the CHA 2 DS 2 -VASc score (AUC 0.750) in predicting "high-risk" AF patients who developed AMI. However, the predictive accuracy of the two clinical-based risk scores was fair. The CHA 2 DS 2 -VASc score has fair predictive value for identifying high-risk patients with AF and is not significantly superior to CHADS 2 in predicting patients who develop AMI.

Early gross motor skills predict the subsequent development of language in children with autism spectrum disorder

PubMed Central

Pickles, Andrew; Lord, Catherine

2015-01-01

Background: Motor milestones such as the onset of walking are important developmental markers, not only for later motor skills but also for more widespread social‐cognitive development. The aim of the current study was to test whether gross motor abilities, specifically the onset of walking, predicted the subsequent rate of language development in a large cohort of children with autism spectrum disorder (ASD). Methods: We ran growth curve models for expressive and receptive language measured at 2, 3, 5 and 9 years in 209 autistic children. Measures of gross motor, visual reception and autism symptoms were collected at the 2 year visit. In Model 1, walking onset was included as a predictor of the slope of language development. Model 2 included a measure of non‐verbal IQ and autism symptom severity as covariates. The final model, Model 3, additionally covaried for gross motor ability. Results: In the first model, parent‐reported age of walking onset significantly predicted the subsequent rate of language development although the relationship became non‐significant when gross motor skill, non‐verbal ability and autism severity scores were included (Models 2 & 3). Gross motor score, however, did remain a significant predictor of both expressive and receptive language development. Conclusions: Taken together, the model results provide some evidence that early motor abilities in young children with ASD can have longitudinal cross‐domain influences, potentially contributing, in part, to the linguistic difficulties that characterise ASD. Autism Res 2016, 9: 993–1001. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research PMID:26692550

Early gross motor skills predict the subsequent development of language in children with autism spectrum disorder.

PubMed

Bedford, Rachael; Pickles, Andrew; Lord, Catherine

2016-09-01

Motor milestones such as the onset of walking are important developmental markers, not only for later motor skills but also for more widespread social-cognitive development. The aim of the current study was to test whether gross motor abilities, specifically the onset of walking, predicted the subsequent rate of language development in a large cohort of children with autism spectrum disorder (ASD). We ran growth curve models for expressive and receptive language measured at 2, 3, 5 and 9 years in 209 autistic children. Measures of gross motor, visual reception and autism symptoms were collected at the 2 year visit. In Model 1, walking onset was included as a predictor of the slope of language development. Model 2 included a measure of non-verbal IQ and autism symptom severity as covariates. The final model, Model 3, additionally covaried for gross motor ability. In the first model, parent-reported age of walking onset significantly predicted the subsequent rate of language development although the relationship became non-significant when gross motor skill, non-verbal ability and autism severity scores were included (Models 2 & 3). Gross motor score, however, did remain a significant predictor of both expressive and receptive language development. Taken together, the model results provide some evidence that early motor abilities in young children with ASD can have longitudinal cross-domain influences, potentially contributing, in part, to the linguistic difficulties that characterise ASD. Autism Res 2016, 9: 993-1001. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

The Chinese-Western Intercultural Couple Standards Scale.

PubMed

Hiew, Danika N; Halford, W Kim; van de Vijver, Fons J R; Liu, Shuang

2015-09-01

We developed the Chinese-Western Intercultural Couple Standards Scale (CWICSS) to assess relationship standards that may differ between Chinese and Western partners and may challenge intercultural couples. The scale assesses 4 Western-derived relationship standards (demonstrations of love, demonstrations of caring, intimacy expression, and intimacy responsiveness) and 4 Chinese-derived relationship standards (relations with the extended family, relational harmony, face, and gender roles). We administered the CWICSS to 983 Chinese and Western participants living in Australia to assess the psychometric properties of the scores as measures of respondents' relationship standards. The CWICSS has a 2-level factor structure with the items reflecting the 8 predicted standards. The 4 Western derived standards loaded onto a higher order factor of couple bond, and the 4 Chinese derived standards loaded onto a higher order factor of family responsibility. The scale scores were structurally equivalent across cultures, genders, and 2 independent samples, and good convergent and discriminant validity was found for the interpretation of scale scores as respondents' endorsement of the predicted standards. Scores on the 8 scales and 2 superordinate scales showed high internal consistency and test-retest coefficients. Chinese endorsed all 4 family responsibility standards more strongly than did Westerners, but Chinese and Western participants were similar in endorsement of couple bond standards. Across both cultures, couple bond standards were endorsed more highly than were family responsibility standards. The CWICSS assesses potential areas of conflict in Chinese-Western relationships. (c) 2015 APA, all rights reserved.

A novel scoring system for predicting adherent placenta in women with placenta previa.

PubMed

Tanimura, Kenji; Morizane, Mayumi; Deguchi, Masashi; Ebina, Yasuhiko; Tanaka, Utaru; Ueno, Yoshiko; Kitajima, Kazuhiro; Maeda, Tetsuo; Sugimura, Kazuro; Yamada, Hideto

2018-04-01

Placenta previa (PP) is one of the most significant risk factors for adherent placenta (AP). The aim of this study was to evaluate the diagnostic efficacy of a novel scoring system for predicting AP in pregnant women with PP. This prospective cohort study enrolled 175 women with PP. The placenta previa with adherent placenta score (PPAP score) is composed of 2 categories: (1) past history of cesarean section (CS), surgical abortion, and/or uterine surgery; and (2) ultrasonography and magnetic resonance imaging findings. Each category is graded as 0, 1, 2, or 4 points, yielding a total score between 0 and 24. When women with PP had PPAP score ≥8, they were considered to be at a high risk for AP and received placement of preoperative internal iliac artery occlusion balloon catheters. If they were found to have AP during CS, they underwent hysterectomy or placenta removal using advanced bipolar with balloon catheter occlusion. The predictive accuracy of PPAP score was evaluated. In total, 23 of the 175 women with PP were diagnosed as having AP, histopathologically or clinically. Twenty-one of 24 women with PPAP score ≥8 had AP, whereas two of 151 women with PPAP score <8 had AP. The scoring system yielded 91.3% sensitivity, 98.0% specificity, 87.5% positive predictive value, and 98.7% negative predictive value for predicting AP in women with PP. This prospective study demonstrated that PPAP scoring system may be useful for predicting AP in women with PP. Copyright © 2018 Elsevier Ltd. All rights reserved.

The autophagy marker LC3 strongly predicts immediate mortality after surgical resection for hepatocellular carcinoma.

PubMed

Lin, Chih-Wen; Lin, Chih-Che; Lee, Po-Huang; Lo, Gin-Ho; Hsieh, Pei-Min; Koh, Kah Wee; Lee, Chih-Yuan; Chen, Yao-Li; Dai, Chia-Yen; Huang, Jee-Fu; Chuang, Wang-Long; Chen, Yaw-Sen; Yu, Ming-Lung

2017-11-03

The remnant liver's ability to regenerate may affect post-hepatectomy immediate mortality. The promotion of autophagy post-hepatectomy could enhance liver regeneration and reduce mortality. This study aimed to identify predictive factors of immediate mortality after surgical resection for hepatocellular carcinoma (HCC). A total of 535 consecutive HCC patients who had undergone their first surgical resection in Taiwan were enrolled between 2010 and 2014. Clinicopathological data and immediate mortality, defined as all cause-mortality within three months after surgery, were analyzed. The expression of autophagy proteins (LC3, Beclin-1, and p62) in adjacent non-tumor tissues was scored by immunohistochemical staining. Approximately 5% of patients had immediate mortality after surgery. The absence of LC3, hypoalbuminemia (<3.5 g/dl), high alanine aminotransferase, and major liver surgery were significantly associated with immediate mortality in univariate analyses. Multivariate logistic regression demonstrated that absence of LC3 (hazard ratio/95% confidence interval: 40.8/5.14-325) and hypoalbuminemia (2.88/1.11-7.52) were significantly associated with immediate mortality. The 3-month cumulative incidence of mortality was 12.1%, 13.0%, 21.4% and 0.4%, respectively, among patients with absence of LC3 expression, hypoalbuminemia, both, or neither of the two. In conclusion, the absence of LC3 expression in adjacent non-tumor tissues and hypoalbuminemia were strongly predictive of immediate mortality after resection for HCC.

Do in-training evaluation reports deserve their bad reputations? A study of the reliability and predictive ability of ITER scores and narrative comments.

PubMed

Ginsburg, Shiphra; Eva, Kevin; Regehr, Glenn

2013-10-01

Although scores on in-training evaluation reports (ITERs) are often criticized for poor reliability and validity, ITER comments may yield valuable information. The authors assessed across-rotation reliability of ITER scores in one internal medicine program, ability of ITER scores and comments to predict postgraduate year three (PGY3) performance, and reliability and incremental predictive validity of attendings' analysis of written comments. Numeric and narrative data from the first two years of ITERs for one cohort of residents at the University of Toronto Faculty of Medicine (2009-2011) were assessed for reliability and predictive validity of third-year performance. Twenty-four faculty attendings rank-ordered comments (without scores) such that each resident was ranked by three faculty. Mean ITER scores and comment rankings were submitted to regression analyses; dependent variables were PGY3 ITER scores and program directors' rankings. Reliabilities of ITER scores across nine rotations for 63 residents were 0.53 for both postgraduate year one (PGY1) and postgraduate year two (PGY2). Interrater reliabilities across three attendings' rankings were 0.83 for PGY1 and 0.79 for PGY2. There were strong correlations between ITER scores and comments within each year (0.72 and 0.70). Regressions revealed that PGY1 and PGY2 ITER scores collectively explained 25% of variance in PGY3 scores and 46% of variance in PGY3 rankings. Comment rankings did not improve predictions. ITER scores across multiple rotations showed decent reliability and predictive validity. Comment ranks did not add to the predictive ability, but correlation analyses suggest that trainee performance can be measured through these comments.

A Machine Learning Approach to Discover Rules for Expressive Performance Actions in Jazz Guitar Music.

PubMed

Giraldo, Sergio I; Ramirez, Rafael

2016-01-01

Expert musicians introduce expression in their performances by manipulating sound properties such as timing, energy, pitch, and timbre. Here, we present a data driven computational approach to induce expressive performance rule models for note duration, onset, energy, and ornamentation transformations in jazz guitar music. We extract high-level features from a set of 16 commercial audio recordings (and corresponding music scores) of jazz guitarist Grant Green in order to characterize the expression in the pieces. We apply machine learning techniques to the resulting features to learn expressive performance rule models. We (1) quantitatively evaluate the accuracy of the induced models, (2) analyse the relative importance of the considered musical features, (3) discuss some of the learnt expressive performance rules in the context of previous work, and (4) assess their generailty. The accuracies of the induced predictive models is significantly above base-line levels indicating that the audio performances and the musical features extracted contain sufficient information to automatically learn informative expressive performance patterns. Feature analysis shows that the most important musical features for predicting expressive transformations are note duration, pitch, metrical strength, phrase position, Narmour structure, and tempo and key of the piece. Similarities and differences between the induced expressive rules and the rules reported in the literature were found. Differences may be due to the fact that most previously studied performance data has consisted of classical music recordings. Finally, the rules' performer specificity/generality is assessed by applying the induced rules to performances of the same pieces performed by two other professional jazz guitar players. Results show a consistency in the ornamentation patterns between Grant Green and the other two musicians, which may be interpreted as a good indicator for generality of the ornamentation rules.

A Machine Learning Approach to Discover Rules for Expressive Performance Actions in Jazz Guitar Music

PubMed Central

Giraldo, Sergio I.; Ramirez, Rafael

2016-01-01

Expert musicians introduce expression in their performances by manipulating sound properties such as timing, energy, pitch, and timbre. Here, we present a data driven computational approach to induce expressive performance rule models for note duration, onset, energy, and ornamentation transformations in jazz guitar music. We extract high-level features from a set of 16 commercial audio recordings (and corresponding music scores) of jazz guitarist Grant Green in order to characterize the expression in the pieces. We apply machine learning techniques to the resulting features to learn expressive performance rule models. We (1) quantitatively evaluate the accuracy of the induced models, (2) analyse the relative importance of the considered musical features, (3) discuss some of the learnt expressive performance rules in the context of previous work, and (4) assess their generailty. The accuracies of the induced predictive models is significantly above base-line levels indicating that the audio performances and the musical features extracted contain sufficient information to automatically learn informative expressive performance patterns. Feature analysis shows that the most important musical features for predicting expressive transformations are note duration, pitch, metrical strength, phrase position, Narmour structure, and tempo and key of the piece. Similarities and differences between the induced expressive rules and the rules reported in the literature were found. Differences may be due to the fact that most previously studied performance data has consisted of classical music recordings. Finally, the rules' performer specificity/generality is assessed by applying the induced rules to performances of the same pieces performed by two other professional jazz guitar players. Results show a consistency in the ornamentation patterns between Grant Green and the other two musicians, which may be interpreted as a good indicator for generality of the ornamentation rules. PMID:28066290

Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism.

PubMed

Karagiannis, George S; Pastoriza, Jessica M; Wang, Yarong; Harney, Allison S; Entenberg, David; Pignatelli, Jeanine; Sharma, Ved P; Xue, Emily A; Cheng, Esther; D'Alfonso, Timothy M; Jones, Joan G; Anampa, Jesus; Rohan, Thomas E; Sparano, Joseph A; Condeelis, John S; Oktay, Maja H

2017-07-05

Breast cancer cells disseminate through TIE2/MENA Calc /MENA INV -dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENA INV isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination. Chemotherapy-induced TMEM activity and cancer cell dissemination were reversed by either administration of the TIE2 inhibitor rebastinib or knockdown of the MENA gene. Our results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy. Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.

PubMed

Kastelein, Florine; Biermann, Katharina; Steyerberg, Ewout W; Verheij, Joanne; Kalisvaart, Marit; Looijenga, Leendert H J; Stoop, Hans A; Walter, Laurens; Kuipers, Ernst J; Spaander, Manon C W; Bruno, Marco J

2013-12-01

The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO. We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome. During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

PubMed

Gambichler, T; Rooms, I; Scholl, L; Stockfleth, E; Stücker, M; Sand, M

2016-11-01

Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. We aimed to investigate Bim protein expression in cutaneous melanoma (CM). Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target. © 2016 European Academy of Dermatology and Venereology.

Validation of the GILLS score for tongue-lip adhesion in Robin sequence patients.

PubMed

Abramowicz, Shelly; Bacic, Janine D; Mulliken, John B; Rogers, Gary F

2012-03-01

The GILLS score consists of gastroesophageal reflux disease, preoperative intubation, late surgical intervention, low birth weight, and syndromic diagnosis. The purpose of this study was to test the validity of the GILLS score in predicting success of tongue-lip adhesion (TLA) in managing Robin sequence. Infants with Robin sequence were included in the study if they had a TLA for airway compromise subsequent to formulation of the GILLS scoring system, that is, they were not included in the original GILLS analysis. The patients were prospectively considered based on the presence of the 5 factors that constitute the GILLS score. A score of ≤ 2 predicts success of TLA. Twenty patients met the inclusion criteria. Tongue-lip adhesion managed the compromised airway in 18 (90%) of 20 patients. Overall, the GILLS score had a sensitivity of 83%, specificity of 50%, positive predictive value of 94%, and negative predictive value of 25%. The GILLS score accurately predicts a successful outcome for TLA in infants with Robin sequence. For infants with a score of 2 or less, TLA is the procedure of choice. Infants with a GILLS score of 3 or greater were 5 times more likely to fail TLA than those with a score of 2 or less. In these patients, other methods of managing the airway should be considered.

Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

PubMed

DeBoer, Mark D; Lee, Arthur M; Herbert, Kirabo; Long, Jin; Thayu, Meena; Griffin, Lindsay M; Baldassano, Robert N; Denson, Lee A; Zemel, Babette S; Denburg, Michelle R; Herskovitz, Rita; Leonard, Mary B

2018-03-01

Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD. Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores. IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

Conceptual scoring of receptive and expressive vocabulary measures in simultaneous and sequential bilingual children.

PubMed

Gross, Megan; Buac, Milijana; Kaushanskaya, Margarita

2014-11-01

The authors examined the effects of conceptual scoring on the performance of simultaneous and sequential bilinguals on standardized receptive and expressive vocabulary measures in English and Spanish. Participants included 40 English-speaking monolingual children, 39 simultaneous Spanish-English bilingual children, and 19 sequential bilingual children, ages 5-7. The children completed standardized receptive and expressive vocabulary measures in English and also in Spanish for those who were bilingual. After the standardized administration, bilingual children were given the opportunity to respond to missed items in their other language to obtain a conceptual score. Controlling for group differences in socioeconomic status (SES), both simultaneous and sequential bilingual children scored significantly below monolingual children on single-language measures of English receptive and expressive vocabulary. Conceptual scoring removed the significant difference between monolingual and simultaneous bilingual children in the receptive modality but not in the expressive modality; differences remained between monolingual and sequential bilingual children in both modalities. However, in both bilingual groups, conceptual scoring increased the proportion of children with vocabulary scores within the average range. Conceptual scoring does not fully ameliorate the bias inherent in single-language standardized vocabulary measures for bilingual children, but the procedures employed here may assist in ruling out vocabulary deficits, particularly in typically developing simultaneous bilingual children.

Conceptual scoring of receptive and expressive vocabulary measures in simultaneous and sequential bilingual children

PubMed Central

Gross, Megan; Buac, Milijana; Kaushanskaya, Margarita

2014-01-01

Purpose This study examined the effects of conceptual scoring on the performance of simultaneous and sequential bilinguals on standardized receptive and expressive vocabulary measures in English and Spanish. Method Participants included 40 English-speaking monolingual children, 39 simultaneous Spanish-English bilingual children, and 19 sequential bilinguals, ages 5–7. The children completed standardized receptive and expressive vocabulary measures in English and also in Spanish for bilinguals. After the standardized administration, bilinguals were given the opportunity to respond to missed items in their other language to obtain a conceptual score. Results Controlling for group differences in socioeconomic status (SES), both simultaneous and sequential bilinguals scored significantly below monolinguals on single-language measures of English receptive and expressive vocabulary. Conceptual scoring removed the significant difference between monolinguals and simultaneous bilinguals in the receptive modality, but not in the expressive modality; differences remained between monolinguals and sequential bilinguals in both modalities. However, in both bilingual groups conceptual scoring increased the proportion of children with vocabulary scores within the average range. Conclusions Conceptual scoring does not fully ameliorate the bias inherent in single-language standardized vocabulary measures for bilinguals, but the procedures employed here may assist in ruling out vocabulary deficits, particularly in typically-developing simultaneous bilingual children. PMID:24811415

The role of HATCH score in predicting the success rate of sinus rhythm following electrical cardioversion of atrial fibrillation.

PubMed

Emren, Sadık Volkan; Kocabaş, Uğur; Duygu, Hamza; Levent, Fatih; Şimşek, Ersin Çağrı; Yapan Emren, Zeynep; Tülüce, Selcen

2016-01-01

The HATCH score predicts the development of persistent and permanent atrial fibrillation (AF) one year after spontaneous or pharmacological conversion to sinus rhythm in patients with AF. However, it remains unknown whether HATCH score predicts short-term success of the procedure at early stages for patients who have undergone electrical cardioversion (EC) for AF. The present study evaluated whether HATCH score predicts short-term success of EC in patients with AF. The study included patients aged 18 years and over, who had undergone EC due to AF lasting less than 12 months, between December 2011 and October 2013. HATCH score was calculated for all patients. The acronym HATCH stands for Hypertension, Age (above 75 years), Transient ischaemic attack or stroke, Chronic obstructive pulmonary disease, and Heart failure. This scoring system awards two points for heart failure and transient ischaemic attack or stroke and one point for the remaining items. The study included 227 patients and short-term EC was successful in 163 of the cases. The mean HATCH scores of the patients who had undergone successful or unsuccessful EC were 1.3 ± 1.4 and 2.9 ± 1.4, respectively (p < 0.001). The area of the HATCH score under the curve in receiver operating characteristics analysis was (AUC) 0.792 (95% CI 0.727-0.857, p < 0.001). A HATCH score of two and above yielded 77% sensitivity, 62% specificity, 56% positive predictive value, and 87% negative predictive value in predicting unsuccessful cardioversion. HATCH score is useful in predicting short-term success of EC at early stages for patients with AF, for whom the use of a rhythm-control strategy is planned.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control

PubMed Central

Burzynski, Grzegorz M.; Reed, Xylena; Taher, Leila; Stine, Zachary E.; Matsui, Takeshi; Ovcharenko, Ivan; McCallion, Andrew S.

2012-01-01

Illuminating the primary sequence encryption of enhancers is central to understanding the regulatory architecture of genomes. We have developed a machine learning approach to decipher motif patterns of hindbrain enhancers and identify 40,000 sequences in the human genome that we predict display regulatory control that includes the hindbrain. Consistent with their roles in hindbrain patterning, MEIS1, NKX6-1, as well as HOX and POU family binding motifs contributed strongly to this enhancer model. Predicted hindbrain enhancers are overrepresented at genes expressed in hindbrain and associated with nervous system development, and primarily reside in the areas of open chromatin. In addition, 77 (0.2%) of these predictions are identified as hindbrain enhancers on the VISTA Enhancer Browser, and 26,000 (60%) overlap enhancer marks (H3K4me1 or H3K27ac). To validate these putative hindbrain enhancers, we selected 55 elements distributed throughout our predictions and six low scoring controls for evaluation in a zebrafish transgenic assay. When assayed in mosaic transgenic embryos, 51/55 elements directed expression in the central nervous system. Furthermore, 30/34 (88%) predicted enhancers analyzed in stable zebrafish transgenic lines directed expression in the larval zebrafish hindbrain. Subsequent analysis of sequence fragments selected based upon motif clustering further confirmed the critical role of the motifs contributing to the classifier. Our results demonstrate the existence of a primary sequence code characteristic to hindbrain enhancers. This code can be accurately extracted using machine-learning approaches and applied successfully for de novo identification of hindbrain enhancers. This study represents a critical step toward the dissection of regulatory control in specific neuronal subtypes. PMID:22759862

Serial evaluation of the MODS, SOFA and LOD scores to predict ICU mortality in mixed critically ill patients.

PubMed

Khwannimit, Bodin

2008-09-01

To perform a serial assessment and compare ability in predicting the intensive care unit (ICU) mortality of the multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) and logistic organ dysfunction (LOD) score. The data were collected prospectively on consecutive ICU admissions over a 24-month period at a tertiary referral university hospital. The MODS, SOFA, and LOD scores were calculated on initial and repeated every 24 hrs. Two thousand fifty four patients were enrolled in the present study. The maximum and delta-scores of all the organ dysfunction scores correlated with ICU mortality. The maximum score of all models had better ability for predicting ICU mortality than initial or delta score. The areas under the receiver operating characteristic curve (AUC) for maximum scores was 0.892 for the MODS, 0.907 for the SOFA, and 0.92for the LOD. No statistical difference existed between all maximum scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Serial assessment of organ dysfunction during the ICU stay is reliable with ICU mortality. The maximum scores is the best discrimination comparable with APACHE II score in predicting ICU mortality.

DCMDN: Deep Convolutional Mixture Density Network

NASA Astrophysics Data System (ADS)

D'Isanto, Antonio; Polsterer, Kai Lars

2017-09-01

Deep Convolutional Mixture Density Network (DCMDN) estimates probabilistic photometric redshift directly from multi-band imaging data by combining a version of a deep convolutional network with a mixture density network. The estimates are expressed as Gaussian mixture models representing the probability density functions (PDFs) in the redshift space. In addition to the traditional scores, the continuous ranked probability score (CRPS) and the probability integral transform (PIT) are applied as performance criteria. DCMDN is able to predict redshift PDFs independently from the type of source, e.g. galaxies, quasars or stars and renders pre-classification of objects and feature extraction unnecessary; the method is extremely general and allows the solving of any kind of probabilistic regression problems based on imaging data, such as estimating metallicity or star formation rate in galaxies.

Cumulative Risk on the Oxytocin Receptor Gene (OXTR) Predicts Empathic Communication by Physician Assistant Students.

PubMed

Floyd, Kory; Generous, Mark Alan; Clark, Lou; McLeod, Ian; Simon, Albert

2017-10-01

In the relationship between patients and health care providers, few communicative features are as significant as the providers' ability to express empathy. A robust empirical literature describes the importance of physician communication skills-particularly those that convey empathy-yet few studies have examined empathic communication by physician assistants, who provide primary care for an increasing number of Americans. The present study examines the empathic communication of physician assistant students in interactions with standardized patients. Over a 6-month period, each student conducted three clinical interviews, each of which was evaluated for empathic communication by the patients, the students' clinical instructors, and third-party observers. Students also provided saliva samples for genotyping six single-nucleotide polymorphisms on the oxytocin receptor gene (OXTR) that are linked empirically to empathic behavior. Consistent with recent research, this study adopted a cumulative risk approach wherein students were scored for their number of risky alleles on the single-nucleotide polymorphisms. Results indicated that cumulative risk on OXTR receptor gene predicted lower patient empathy scores as rated by instructors and observers, but not by standardized patients.

Mortality Prediction Using Acute Physiology and Chronic Health Evaluation II and Acute Physiology and Chronic Health Evaluation IV Scoring Systems: Is There a Difference?

PubMed Central

Venkataraman, Ramesh; Gopichandran, Vijayaprasad; Ranganathan, Lakshmi; Rajagopal, Senthilkumar; Abraham, Babu K; Ramakrishnan, Nagarajan

2018-01-01

Background: Mortality prediction in the Intensive Care Unit (ICU) setting is complex, and there are several scoring systems utilized for this process. The Acute Physiology and Chronic Health Evaluation (APACHE) II has been the most widely used scoring system; although, the more recent APACHE IV is considered an updated and advanced prediction model. However, these two systems may not give similar mortality predictions. Objectives: The aim of this study is to compare the mortality prediction ability of APACHE II and APACHE IV scoring systems among patients admitted to a tertiary care ICU. Methods: In this prospective longitudinal observational study, APACHE II and APACHE IV scores of ICU patients were computed using an online calculator. The outcome of the ICU admissions for all the patients was collected as discharged or deceased. The data were analyzed to compare the discrimination and calibration of the mortality prediction ability of the two scores. Results: Out of the 1670 patients' data analyzed, the area under the receiver operating characteristic of APACHE II score was 0.906 (95% confidence interval [CI] – 0.890–0.992), and APACHE IV score was 0.881 (95% CI – 0.862–0.890). The mean predicted mortality rate of the study population as given by the APACHE II scoring system was 44.8 ± 26.7 and as given by APACHE IV scoring system was 29.1 ± 28.5. The observed mortality rate was 22.4%. Conclusions: The APACHE II and IV scoring systems have comparable discrimination ability, but the calibration of APACHE IV seems to be better than that of APACHE II. There is a need to recalibrate the scales with weights derived from the Indian population. PMID:29910542

Mortality Prediction Using Acute Physiology and Chronic Health Evaluation II and Acute Physiology and Chronic Health Evaluation IV Scoring Systems: Is There a Difference?

PubMed

Venkataraman, Ramesh; Gopichandran, Vijayaprasad; Ranganathan, Lakshmi; Rajagopal, Senthilkumar; Abraham, Babu K; Ramakrishnan, Nagarajan

2018-05-01

Mortality prediction in the Intensive Care Unit (ICU) setting is complex, and there are several scoring systems utilized for this process. The Acute Physiology and Chronic Health Evaluation (APACHE) II has been the most widely used scoring system; although, the more recent APACHE IV is considered an updated and advanced prediction model. However, these two systems may not give similar mortality predictions. The aim of this study is to compare the mortality prediction ability of APACHE II and APACHE IV scoring systems among patients admitted to a tertiary care ICU. In this prospective longitudinal observational study, APACHE II and APACHE IV scores of ICU patients were computed using an online calculator. The outcome of the ICU admissions for all the patients was collected as discharged or deceased. The data were analyzed to compare the discrimination and calibration of the mortality prediction ability of the two scores. Out of the 1670 patients' data analyzed, the area under the receiver operating characteristic of APACHE II score was 0.906 (95% confidence interval [CI] - 0.890-0.992), and APACHE IV score was 0.881 (95% CI - 0.862-0.890). The mean predicted mortality rate of the study population as given by the APACHE II scoring system was 44.8 ± 26.7 and as given by APACHE IV scoring system was 29.1 ± 28.5. The observed mortality rate was 22.4%. The APACHE II and IV scoring systems have comparable discrimination ability, but the calibration of APACHE IV seems to be better than that of APACHE II. There is a need to recalibrate the scales with weights derived from the Indian population.

The AIMS65 score compared with the Glasgow-Blatchford score in predicting outcomes in upper GI bleeding.

PubMed

Hyett, Brian H; Abougergi, Marwan S; Charpentier, Joseph P; Kumar, Navin L; Brozovic, Suzana; Claggett, Brian L; Travis, Anne C; Saltzman, John R

2013-04-01

We previously derived and validated the AIMS65 score, a mortality prognostic scale for upper GI bleeding (UGIB). To validate the AIMS65 score in a different patient population and compare it with the Glasgow-Blatchford risk score (GBRS). Retrospective cohort study. Adults with a primary diagnosis of UGIB. inpatient mortality. composite clinical endpoint of inpatient mortality, rebleeding, and endoscopic, radiologic or surgical intervention; blood transfusion; intensive care unit admission; rebleeding; length of stay; timing of endoscopy. The area under the receiver-operating characteristic curve (AUROC) was calculated for each score. Of the 278 study patients, 6.5% died and 35% experienced the composite clinical endpoint. The AIMS65 score was superior in predicting inpatient mortality (AUROC, 0.93 vs 0.68; P < .001), whereas the GBRS was superior in predicting blood transfusions (AUROC, 0.85 vs 0.65; P < .01) The 2 scores were similar in predicting the composite clinical endpoint (AUROC, 0.62 vs 0.68; P = .13) as well as the secondary outcomes. A GBRS of 10 and 12 or more maximized the sum of the sensitivity and specificity for inpatient mortality and rebleeding, respectively. The cutoff was 2 or more for the AIMS65 score for both outcomes. Retrospective, single-center study. The AIMS65 score is superior to the GBRS in predicting inpatient mortality from UGIB, whereas the GBRS is superior for predicting blood transfusion. Both scores are similar in predicting the composite clinical endpoint and other outcomes in clinical care and resource use. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Predicting dementia using socio-demographic characteristics and the Free and Cued Selective Reminding Test in the general population.

PubMed

Mura, Thibault; Baramova, Marieta; Gabelle, Audrey; Artero, Sylvaine; Dartigues, Jean-François; Amieva, Hélène; Berr, Claudine

2017-03-23

Our study aimed to determine whether the consideration of socio-demographic features improves the prediction of Alzheimer's dementia (AD) at 5 years when using the Free and Cued Selective Reminding Test (FCSRT) in the general older population. Our analyses focused on 2558 subjects from the prospective Three-City Study, a cohort of community-dwelling individuals aged 65 years and over, with FCSRT scores. Four "residual scores" and "risk scores" were built that included the FCSRT scores and socio-demographic variables. The predictive performance of crude, residual and risk scores was analyzed by comparing the areas under the ROC curve (AUC). In total, 1750 subjects were seen 5 years after completing the FCSRT. AD was diagnosed in 116 of them. Compared with the crude free-recall score, the predictive performances of the residual score and of the risk score were not significantly improved (AUC: 0.83 vs 0.82 and 0.88 vs 0.89 respectively). Using socio-demographic features in addition to the FCSRT does not improve its predictive performance for dementia or AD.

Reliability of Modern Scores to Predict Long-Term Mortality After Isolated Aortic Valve Operations.

PubMed

Barili, Fabio; Pacini, Davide; D'Ovidio, Mariangela; Ventura, Martina; Alamanni, Francesco; Di Bartolomeo, Roberto; Grossi, Claudio; Davoli, Marina; Fusco, Danilo; Perucci, Carlo; Parolari, Alessandro

2016-02-01

Contemporary scores for estimating perioperative death have been proposed to also predict also long-term death. The aim of the study was to evaluate the performance of the updated European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons Predicted Risk of Mortality score, and the Age, Creatinine, Left Ventricular Ejection Fraction score for predicting long-term mortality in a contemporary cohort of isolated aortic valve replacement (AVR). We also sought to develop for each score a simple algorithm based on predicted perioperative risk to predict long-term survival. Complete data on 1,444 patients who underwent isolated AVR in a 7-year period were retrieved from three prospective institutional databases and linked with the Italian Tax Register Information System. Data were evaluated with performance analyses and time-to-event semiparametric regression. Survival was 83.0% ± 1.1% at 5 years and 67.8 ± 1.9% at 8 years. Discrimination and calibration of all three scores both worsened for prediction of death at 1 year and 5 years. Nonetheless, a significant relationship was found between long-term survival and quartiles of scores (p < 0.0001). The estimated perioperative risk by each model was used to develop an algorithm to predict long-term death. The hazard ratios for death were 1.1 (95% confidence interval, 1.07 to 1.12) for European System for Cardiac Operative Risk Evaluation II, 1.34 (95% CI, 1.28 to 1.40) for the Society of Thoracic Surgeons score, and 1.08 (95% CI, 1.06 to 1.10) for the Age, Creatinine, Left Ventricular Ejection Fraction score. The predicted risk generated by European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons score, and Age, Creatinine, Left Ventricular Ejection Fraction scores cannot also be considered a direct estimate of the long-term risk for death. Nonetheless, the three scores can be used to derive an estimate of long-term risk of death in patients who undergo isolated AVR with the use of a simple algorithm. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Factors affecting unplanned readmissions from community hospitals to acute hospitals: a prospective observational study.

PubMed

Leong, Ian Y O; Chan, Siew-Pang; Tan, Boon-Yeow; Sitoh, Yih-Yiow; Ang, Yan-Hoon; Merchant, Reshma; Kanagasabai, Kala; Lee, Patricia S Y; Pang, Weng-Sun

2009-02-01

While the readmission rate from community hospitals is known, the factors affecting it are not. Our aim was to determine the factors predicting unplanned readmissions from community hospitals (CHs) to acute hospitals (AHs). This was an observational prospective cohort study, involving 842 patients requiring post-acute rehabilitation in 2 CHs admitted from 3 AHs in Singapore. We studied the role of the Cumulative Illness Rating Scale (CIRS) organ impairment scores, the Mini-mental State Examination (MMSE) score, the Shah modified Barthel Index (BI) score, and the triceps skin fold thickness (TSFT) in predicting the rate of unplanned readmissions (UR), early unplanned readmissions (EUPR) and late unplanned readmissions (LUPR). We developed a clinical prediction rule to determine the risk of UR and EUPR. The rates of EUPR and LUPR were 7.6% and 10.3% respectively. The factors that predicted UR were the CIRS-heart score, the CIRS-haemopoietic score, the CIRS-endocrine / metabolic score and the BI on admission. The MMSE was predictive of EUPR. The TSFT and CIRS-liver score were predictive of LUPR. Upon receiver operator characteristics analysis, the clinical prediction rules for the prediction of EUPR and UR had areas under the curve of 0.745 and 0.733 respectively. The likelihood ratios of the clinical prediction rules for EUPR and UR ranged from 0.42 to 5.69 and 0.34 to 3.16 respectively. Patients who have UR can be identified by the admission BI, the MMSE, the TSFT and CIRS scores in the cardiac, haemopoietic, liver and endocrine/metabolic systems.

Prediction of Beck Depression Inventory (BDI-II) Score Using Acoustic Measurements in a Sample of Iium Engineering Students

NASA Astrophysics Data System (ADS)

Fikri Zanil, Muhamad; Nur Wahidah Nik Hashim, Nik; Azam, Huda

2017-11-01

Psychiatrist currently relies on questionnaires and interviews for psychological assessment. These conservative methods often miss true positives and might lead to death, especially in cases where a patient might be experiencing suicidal predisposition but was only diagnosed as major depressive disorder (MDD). With modern technology, an assessment tool might aid psychiatrist with a more accurate diagnosis and thus hope to reduce casualty. This project will explore on the relationship between speech features of spoken audio signal (reading) in Bahasa Malaysia with the Beck Depression Inventory scores. The speech features used in this project were Power Spectral Density (PSD), Mel-frequency Ceptral Coefficients (MFCC), Transition Parameter, formant and pitch. According to analysis, the optimum combination of speech features to predict BDI-II scores include PSD, MFCC and Transition Parameters. The linear regression approach with sequential forward/backward method was used to predict the BDI-II scores using reading speech. The result showed 0.4096 mean absolute error (MAE) for female reading speech. For male, the BDI-II scores successfully predicted 100% less than 1 scores difference with MAE of 0.098437. A prediction system called Depression Severity Evaluator (DSE) was developed. The DSE managed to predict one out of five subjects. Although the prediction rate was low, the system precisely predict the score within the maximum difference of 4.93 for each person. This demonstrates that the scores are not random numbers.

Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Budoff, Matthew J; Nasir, Khurram; McClelland, Robyn L; Detrano, Robert; Wong, Nathan; Blumenthal, Roger S; Kondos, George; Kronmal, Richard A

2009-01-27

In this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score. The presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units). There were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank. Using absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well.

Predictive models for mortality after ruptured aortic aneurysm repair do not predict futility and are not useful for clinical decision making.

PubMed

Thompson, Patrick C; Dalman, Ronald L; Harris, E John; Chandra, Venita; Lee, Jason T; Mell, Matthew W

2016-12-01

The clinical decision-making utility of scoring algorithms for predicting mortality after ruptured abdominal aortic aneurysms (rAAAs) remains unknown. We sought to determine the clinical utility of the algorithms compared with our clinical decision making and outcomes for management of rAAA during a 10-year period. Patients admitted with a diagnosis rAAA at a large university hospital were identified from 2005 to 2014. The Glasgow Aneurysm Score, Hardman Index, Vancouver Score, Edinburgh Ruptured Aneurysm Score, University of Washington Ruptured Aneurysm Score, Vascular Study Group of New England rAAA Risk Score, and the Artificial Neural Network Score were analyzed for accuracy in predicting mortality. Among patients quantified into the highest-risk group (predicted mortality >80%-85%), we compared the predicted with the actual outcome to determine how well these scores predicted futility. The cohort comprised 64 patients. Of those, 24 (38%) underwent open repair, 36 (56%) underwent endovascular repair, and 4 (6%) received only comfort care. Overall mortality was 30% (open repair, 26%; endovascular repair, 24%; no repair, 100%). As assessed by the scoring systems, 5% to 35% of patients were categorized as high-mortality risk. Intersystem agreement was poor, with κ values ranging from 0.06 to 0.79. Actual mortality was lower than the predicted mortality (50%-70% vs 78%-100%) for all scoring systems, with each scoring system overestimating mortality by 10% to 50%. Mortality rates for patients not designated into the high-risk cohort were dramatically lower, ranging from 7% to 29%. Futility, defined as 100% mortality, was predicted in five of 63 patients with the Hardman Index and in two of 63 of the University of Washington score. Of these, surgery was not offered to one of five and one of two patients, respectively. If one of these two models were used to withhold operative intervention, the mortality of these patients would have been 100%. The actual mortality for these patients was 60% and 50%, respectively. Clinical algorithms for predicting mortality after rAAA were not useful for predicting futility. Most patients with rAAA were not classified in the highest-risk group by the clinical decision models. Among patients identified as highest risk, predicted mortality was overestimated compared with actual mortality. The data from this study support the limited value to surgeons of the currently published algorithms. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Designing Tyrosinase siRNAs by Multiple Prediction Algorithms and Evaluation of Their Anti-Melanogenic Effects.

PubMed

Kwon, Ok-Seon; Kwon, Soo-Jung; Kim, Jin Sang; Lee, Gunbong; Maeng, Han-Joo; Lee, Jeongmi; Hwang, Gwi Seo; Cha, Hyuk-Jin; Chun, Kwang-Hoon

2018-05-01

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥-34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3' overhang at the 3' end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.

Designing Tyrosinase siRNAs by Multiple Prediction Algorithms and Evaluation of Their Anti-Melanogenic Effects

PubMed Central

Kwon, Ok-Seon; Kwon, Soo-Jung; Kim, Jin Sang; Lee, Gunbong; Maeng, Han-Joo; Lee, Jeongmi; Hwang, Gwi Seo; Cha, Hyuk-Jin; Chun, Kwang-Hoon

2018-01-01

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥−34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3′ overhang at the 3′ end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms. PMID:29223142

Striatal dopamine (D2) receptor availability predicts socially desirable responding.

PubMed

Reeves, Suzanne J; Mehta, Mitul A; Montgomery, Andrew J; Amiras, Dimitri; Egerton, Alice; Howard, Robert J; Grasby, Paul M

2007-02-15

Research in non-human primates has implicated striatal dopamine (D2) receptor function in the expression of social dominance--a fundamental component of social extraversion. We predicted that trait extraversion - indexed by the revised Eysenck Personality Questionnaire (EPQ-R) - would correlate with striatal DA (D2) receptor measures - indexed by [(11)C]-Raclopride binding potential (BP) - in 28 healthy post-menopausal females (mean age=75 years; range=58-91 years). Region of interest (ROI) and voxel-based statistical parametric mapping (SPM) analyses were performed, using a reference tissue model for [(11)C]-Raclopride. ROI analysis showed moderately significant negative correlations between extraversion and BP measures in the left caudate and between psychoticism scores and BP in the right putamen. Unexpectedly, scores on the Lie scale, a measure of socially desirable responding, were significantly and negatively correlated with BP measures in the putamen and survived Bonferroni correction on the right side. After controlling for the potential confounding of self-report bias in high Lie scorers, only the correlation between Lie scores and BP measures in the right putamen remained significant. Voxel-based analysis showed only Lie scores to be significantly and negatively correlated with BP measures in the right putamen. We explored this association further by applying an ROI-based approach to data on a previously scanned sample of young adults (n=13) and found a similar pattern of association, which achieved trend level significance in the right putamen. Although unanticipated, the relationship observed between BP measures in the right putamen and Lie scores is consistent with dopaminergic involvement in socially rewarding behaviour. How this relates to dopaminergic tone will need to be further explored.

Gene expression factor analysis to differentiate pathways linked to fibromyalgia, chronic fatigue syndrome, and depression in a diverse patient sample

PubMed Central

Iacob, Eli; Light, Alan R.; Donaldson, Gary W.; Okifuji, Akiko; Hughen, Ronald W.; White, Andrea T.; Light, Kathleen C.

2015-01-01

Objective To determine if independent candidate genes can be grouped into meaningful biological factors and if these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia (FMS) while controlling for co-morbid depression, sex, and age. Methods We included leukocyte mRNA gene expression from a total of 261 individuals including healthy controls (n=61), patients with FMS only (n=15), CFS only (n=33), co-morbid CFS and FMS (n=79), and medication-resistant (n=42) or medication-responsive (n=31) depression. We used Exploratory Factor Analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine if these factors were associated with specific diagnoses. Results EFA resulted in four independent factors with minimal overlap of genes between factors explaining 51% of the variance. We labeled these factors by function as: 1) Purinergic and cellular modulators; 2) Neuronal growth and immune function; 3) Nociception and stress mediators; 4) Energy and mitochondrial function. Regression analysis predicting these biological factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in Factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (QIDS score), but not associated with FMS. Conclusion Expression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters but in opposite directions when controlling for co-morbid FMS. Given high co-morbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression. PMID:26097208

Simplified Mortality Score for the Intensive Care Unit (SMS-ICU): protocol for the development and validation of a bedside clinical prediction rule.

PubMed

Granholm, Anders; Perner, Anders; Krag, Mette; Hjortrup, Peter Buhl; Haase, Nicolai; Holst, Lars Broksø; Marker, Søren; Collet, Marie Oxenbøll; Jensen, Aksel Karl Georg; Møller, Morten Hylander

2017-03-09

Mortality prediction scores are widely used in intensive care units (ICUs) and in research, but their predictive value deteriorates as scores age. Existing mortality prediction scores are imprecise and complex, which increases the risk of missing data and decreases the applicability bedside in daily clinical practice. We propose the development and validation of a new, simple and updated clinical prediction rule: the Simplified Mortality Score for use in the Intensive Care Unit (SMS-ICU). During the first phase of the study, we will develop and internally validate a clinical prediction rule that predicts 90-day mortality on ICU admission. The development sample will comprise 4247 adult critically ill patients acutely admitted to the ICU, enrolled in 5 contemporary high-quality ICU studies/trials. The score will be developed using binary logistic regression analysis with backward stepwise elimination of candidate variables, and subsequently be converted into a point-based clinical prediction rule. The general performance, discrimination and calibration of the score will be evaluated, and the score will be internally validated using bootstrapping. During the second phase of the study, the score will be externally validated in a fully independent sample consisting of 3350 patients included in the ongoing Stress Ulcer Prophylaxis in the Intensive Care Unit trial. We will compare the performance of the SMS-ICU to that of existing scores. We will use data from patients enrolled in studies/trials already approved by the relevant ethical committees and this study requires no further permissions. The results will be reported in accordance with the Transparent Reporting of multivariate prediction models for Individual Prognosis Or Diagnosis (TRIPOD) statement, and submitted to a peer-reviewed journal. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Are the Best Scores the Best Scores for Predicting College Success?

ERIC Educational Resources Information Center

Patterson, Brian F.; Mattern, Krista D.; Swerdzewski, Peter

2012-01-01

The College Board's SAT[R] Score Choice[TM] policy allows students to choose which set(s) of scores to send to colleges and universities to which they plan to apply. Based on data gathered before the implementation of that policy, the following study evaluated the predictive validity of the various sets of SAT scores. The value of five score sets…

TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed.

PubMed

Uramoto, Hidetaka; Onitsuka, Takamitsu; Shimokawa, Hidehiko; Hanagiri, Takeshi

2010-10-01

Recently, pemetrexed (PEM), a new generation antifolate, has been used for the treatment of patients with advanced non-squamous cell carcinoma (SQ) of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). However, no useful markers for selecting appropriate candidates exist at present. Tumor specimens were collected from 5 lung non-SQ and 8 MPM patients who underwent surgery and received PEM. Real-time PCR and immunohistochemical (IHC) staining of the primary tumor were used to analyze the mRNA and protein expressions of thymidylate synthase (TS)/dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), and to compare the expression status and clinical outcomes. TS, DHFR, and GARFT mRNA levels had a median value of 2.39, 1.70, and 1.40 in non-SQ samples of NSCLC patients. The TS and DHFR protein levels had a mean total score of 2 and 4 in non-SQ of NSCLC patients. TS, DHFR, and GARFT mRNA levels had a median value of 5.55, 3.73, and 3.52 in MPM patients. TS and DHFR protein levels had a mean total expression score of 1 and 3 in MPM patients. No significant correlation was identified between the expression levels of TS/DPD/GARFT mRNA and clinical response for the non-SQ of NSCLC and MPM patients treated with PEM. TS, DHFR, and GARFT mRNA and protein expression may not be useful markers for predicting clinical response in Japanese patients with non-SQ of NSCLC and MPM. Further investigations are necessary in order to develop biomarkers to determine the clinical benefits of PEM treatment.

Children's understanding of idioms and theory of mind development.

PubMed

Caillies, Stéphanie; Le Sourn-Bissaoui, Sandrine

2008-09-01

The aim of this study was to test the hypothesis according to which theory of mind competence was a prerequisite to ambiguous idioms understanding. We hypothesized that the child needs to understand that the literal interpretation could be a false world representation, a false belief, and that the speaker's intention is to mean something else, to correctly process idiomatic expressions. Two kinds of ambiguous idioms were of interest: decomposable and nondecomposable expressions (Titone & Connine, 1999). An experiment was designed to assess the figurative developmental changes that occur with theory of mind competence. Five-, 6- and 7-year-old children performed five theory of mind tasks (an appearance-reality task, three false-belief tasks and a second-order false-belief task) and listened to decomposable and nondecomposable idiomatic expressions inserted in context, before performing a multiple choice task. Results indicated that only nondecomposable idiomatic expression was predicted from the theory of mind scores, and particularly from the second-order competences. Results are discussed with respect to theory of mind and verbal competences.

Scores for post-myocardial infarction risk stratification in the community.

PubMed

Singh, Mandeep; Reeder, Guy S; Jacobsen, Steven J; Weston, Susan; Killian, Jill; Roger, Véronique L

2002-10-29

Several scores, most of which were derived from clinical trials, have been proposed for stratifying risk after myocardial infarctions (MIs). Little is known about their generalizability to the community, their respective advantages, and whether the ejection fraction (EF) adds prognostic information to the scores. The purpose of this study is to evaluate the Thrombolysis in Myocardial Infarction (TIMI) and Predicting Risk of Death in Cardiac Disease Tool (PREDICT) scores in a geographically defined MI cohort and determine the incremental value of EF for risk stratification. MIs occurring in Olmsted County were validated with the use of standardized criteria and stratified with the ECG into ST-segment elevation (STEMI) and non-ST-segment elevation (NSTEMI) MI. Logistic regression examined the discriminant accuracy of the TIMI and PREDICT scores to predict death and recurrent MI and assessed the incremental value of the EF. After 6.3+/-4.7 years, survival was similar for the 562 STEMIs and 717 NSTEMIs. The discriminant accuracy of the TIMI score was good in STEMI but only fair in NSTEMI. Across time and end points, irrespective of reperfusion therapy, the discriminant accuracy of the PREDICT score was consistently superior to that of the TIMI scores, largely because PREDICT includes comorbidity; EF provided incremental information over that provided by the scores and comorbidity. In the community, comorbidity and EF convey important prognostic information and should be included in approaches for stratifying risk after MI.

Using the abbreviated injury severity and Glasgow Coma Scale scores to predict 2-week mortality after traumatic brain injury.

PubMed

Timmons, Shelly D; Bee, Tiffany; Webb, Sharon; Diaz-Arrastia, Ramon R; Hesdorffer, Dale

2011-11-01

Prediction of outcome after traumatic brain injury (TBI) remains elusive. We tested the use of a single hospital Glasgow Coma Scale (GCS) Score, GCS Motor Score, and the Head component of the Abbreviated Injury Scale (AIS) Score to predict 2-week cumulative mortality in a large cohort of TBI patients admitted to the eight U.S. Level I trauma centers in the TBI Clinical Trials Network. Data on 2,808 TBI patients were entered into a centralized database. These TBI patients were categorized as severe (GCS score, 3-8), moderate (9-12), or complicated mild (13-15 with positive computed tomography findings). Intubation and chemical paralysis were recorded. The cumulative incidence of mortality in the first 2 weeks after head injury was calculated using Kaplan-Meier survival analysis. Cox proportional hazards regression was used to estimate the magnitude of the risk for 2-week mortality. Two-week cumulative mortality was independently predicted by GCS, GCS Motor Score, and Head AIS. GCS Severity Category and GCS Motor Score were stronger predictors of 2-week mortality than Head AIS. There was also an independent effect of age (<60 vs. ≥60) on mortality after controlling for both GCS and Head AIS Scores. Anatomic and physiologic scales are useful in the prediction of mortality after TBI. We did not demonstrate any added benefit to combining the total GCS or GCS Motor Scores with the Head AIS Score in the short-term prediction of death after TBI.

The Ability of Career Maturity Indicators to Predict Interest Score Differentiation, Consistency, and Elevation.

ERIC Educational Resources Information Center

Miner, Claire Usher; Osborne, W. Larry; Jaeger, Richard M.

1997-01-01

Uses regression analysis on career development measures to examine whether career maturity indicators are predictive of interest consistency, differentiation, and score elevation. Results indicate that interest consistency and score elevation were weakly predicted by the measure; no relationship existed between the attitudinal and cognitive…

Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment.

PubMed

Levey, D F; Niculescu, E M; Le-Niculescu, H; Dainton, H L; Phalen, P L; Ladd, T B; Weber, H; Belanger, E; Graham, D L; Khan, F N; Vanipenta, N P; Stage, E C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R; Niculescu, A B

2016-06-01

Women are under-represented in research on suicidality to date. Although women have a lower rate of suicide completion than men, due in part to the less-violent methods used, they have a higher rate of suicide attempts. Our group has previously identified genomic (blood gene expression biomarkers) and clinical information (apps) predictors for suicidality in men. We now describe pilot studies in women. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation (no SI) and high suicidal ideation (high SI) states (n=12 participants out of a cohort of 51 women psychiatric participants followed longitudinally, with diagnoses of bipolar disorder, depression, schizoaffective disorder and schizophrenia). We then used a Convergent Functional Genomics (CFG) approach to prioritize the candidate biomarkers identified in the discovery step by using all the prior evidence in the field. Next, we validated for suicidal behavior the top-ranked biomarkers for SI, in a demographically matched cohort of women suicide completers from the coroner's office (n=6), by assessing which markers were stepwise changed from no SI to high SI to suicide completers. We then tested the 50 biomarkers that survived Bonferroni correction in the validation step, as well as top increased and decreased biomarkers from the discovery and prioritization steps, in a completely independent test cohort of women psychiatric disorder participants for prediction of SI (n=33) and in a future follow-up cohort of psychiatric disorder participants for prediction of psychiatric hospitalizations due to suicidality (n=24). Additionally, we examined how two clinical instruments in the form of apps, Convergent Functional Information for Suicidality (CFI-S) and Simplified Affective State Scale (SASS), previously tested in men, perform in women. The top CFI-S item distinguishing high SI from no SI states was the chronic stress of social isolation. We then showed how the clinical information apps combined with the 50 validated biomarkers into a broad predictor (UP-Suicide), our apriori primary end point, predicts suicidality in women. UP-Suicide had a receiver-operating characteristic (ROC) area under the curve (AUC) of 82% for predicting SI and an AUC of 78% for predicting future hospitalizations for suicidality. Some of the individual components of the UP-Suicide showed even better results. SASS had an AUC of 81% for predicting SI, CFI-S had an AUC of 84% and the combination of the two apps had an AUC of 87%. The top biomarker from our sequential discovery, prioritization and validation steps, BCL2, predicted future hospitalizations due to suicidality with an AUC of 89%, and the panel of 50 validated biomarkers (BioM-50) predicted future hospitalizations due to suicidality with an AUC of 94%. The best overall single blood biomarker for predictions was PIK3C3 with an AUC of 65% for SI and an AUC of 90% for future hospitalizations. Finally, we sought to understand the biology of the biomarkers. BCL2 and GSK3B, the top CFG scoring validated biomarkers, as well as PIK3C3, have anti-apoptotic and neurotrophic effects, are decreased in expression in suicidality and are known targets of the anti-suicidal mood stabilizer drug lithium, which increases their expression and/or activity. Circadian clock genes were overrepresented among the top markers. Notably, PER1, increased in expression in suicidality, had an AUC of 84% for predicting future hospitalizations, and CSNK1A1, decreased in expression, had an AUC of 96% for predicting future hospitalizations. Circadian clock abnormalities are related to mood disorder, and sleep abnormalities have been implicated in suicide. Docosahexaenoic acid signaling was one of the top biological pathways overrepresented in validated biomarkers, which is of interest given the potential therapeutic and prophylactic benefits of omega-3 fatty acids. Some of the top biomarkers from the current work in women showed co-directionality of change in expression with our previous work in men, whereas others had changes in opposite directions, underlying the issue of biological context and differences in suicidality between the two genders. With this study, we begin to shed much needed light in the area of female suicidality, identify useful objective predictors and help understand gender commonalities and differences. During the conduct of the study, one participant committed suicide. In retrospect, when the analyses were completed, her UP-Suicide risk prediction score was at the 100 percentile of all participants tested.

Detection of survivin mRNA in healthy oral mucosa, oral leucoplakia and oral cancer.

PubMed

Lodi, G; Franchini, R; Bez, C; Sardella, A; Moneghini, L; Pellegrini, C; Bosari, S; Manfredi, M; Vescovi, P; Carrassi, A

2010-01-01

Survivin is involved in modulation of cell death and cell division processes. Survivin expression in normal adult tissues has not been fully understood, although it is markedly lower than in cancer, where it is over-expressed. To investigate survivin expression in normal, potentially malignant and cancerous oral mucosa. We measured survivin mRNA levels by real-time RT-PCR in specimens of oral mucosa (15 from normal mucosa, 17 from potentially malignant lesions, 17 from neoplasms). Scores were compared using Kruskal-Wallis test and post hoc according to Conover. Chi-squared test was used for dichotomous data. The median relative levels of survivin mRNA resulted six for normal mucosa, eight for potentially malignant lesions, 13 for cancers: differences among these three groups were statistically significant, as between cancer and potentially malignant lesions. Expression in normal mucosa and potentially lesions group showed no significant difference. Low, but not marginal expression of survivin in normal mucosa is a new finding, and it could be explained with the higher sensibility of our methods. Survivin expression in oral potentially malignant lesions might indicate a progressive deregulation of expression paralleling oncogenesis, particularly during the first stages of process, suggesting a putative predictive role for survivin.

Comparison of CHA2DS2-VASc, CHADS2 and HATCH scores for the prediction of new-onset atrial fibrillation in cancer patients: A nationwide cohort study of 760,339 study participants with competing risk analysis.

PubMed

Hu, Wei-Syun; Lin, Cheng-Li

2017-11-01

The current study was conducted to assess the ability of CHA 2 DS 2 -VASc, CHADS 2 and HATCH scores in predicting new-onset atrial fibrillation (AF) among patients with cancer. Patients with newly diagnosed cancer between 1 January, 2000 and 31 December, 2011, from the Registry for Catastrophic Illness Patient Database, were defined as the study cohort. CHA 2 DS 2 -VASc, CHADS 2 and HATCH scores were used for new-onset AF prediction in these study patients, and the predictive accuracy of the scores was assessed by the receiver operating characteristics (ROC) curve. A total of 760,339 cancer patients were identified as the study participants. The ROC curves were 0.68 (95% confidence interval [CI] = 0.68-0.69) for the CHA 2 DS 2 -VASc score, 0.67 (95% CI = 0.67-0.68) for the CHADS 2 score and 0.69 (95% CI = 0.69-0.70) for the HATCH score. There were significant differences of c-statistics among CHA 2 DS 2 -VASc score, CHADS 2 score and HATCH score (CHA 2 DS 2 -VASc score vs. CHADS 2 score, p = 0.01; CHA 2 DS 2 -VASc score vs. HATCH score, p = 0.002; CHADS 2 score vs. HATCH score, p < 0.001). The current study is the first to assess the prognostic value of 3 AF risk scores (CHA 2 DS 2 -VASc, CHADS 2 and HATCH scores) in patients with newly-diagnosed cancer. HATCH score was found to have a slightly but significantly better predictive performance than the other 2 scores. Copyright © 2017 Elsevier B.V. All rights reserved.

[Determination of prognostic value of the OESIL risk score at 6 months in a Colombian cohort with syncope evaluated in the emergency department; first Latin American experience].

PubMed

Díaz-Tribaldos, Diana Carolina; Mora, Guillermo; Olaya, Alejandro; Marín, Jorge; Sierra Matamoros, Fabio

2017-07-14

To establish the prognostic value, with sensitivity, specificity, positive predictive value, and negative predictive value for the OESIL syncope risk score to predict the presentation of severe outcomes (death, invasive interventions, and readmission) after 6 months of observation in adults who consulted the emergency department due to syncope. Observational, prospective, and multicentre study with enrolment of subjects older than 18 years, who consulted in the emergency department due to syncope. A record was mad of the demographic and clinical information of all patients. The OESIL risk score was calculated, and severe patient outcomes were followed up during a 6 month period using telephone contact. A total of 161 patients met the inclusion criteria and were followed up for 6 months. A score above or equal to 2 in the risk score, classified as high risk, was present in 72% of the patients. The characteristics of the risk score to predict the combined outcome of mortality, invasive interventions, and readmission for a score above or equal to 2 were 75.7, 30.5, 43.1, and 64.4% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively. A score above or equal to 2 in the OESIL risk score applied in Colombian population was of limited use to predict the studied severe outcomes. This score will be unable to discriminate between patients that benefit of early admission and further clinical studies. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-03-01

While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH. All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Poor performances of EuroSCORE and CARE score for prediction of perioperative mortality in octogenarians undergoing aortic valve replacement for aortic stenosis.

PubMed

Chhor, Vibol; Merceron, Sybille; Ricome, Sylvie; Baron, Gabriel; Daoud, Omar; Dilly, Marie-Pierre; Aubier, Benjamin; Provenchere, Sophie; Philip, Ivan

2010-08-01

Although results of cardiac surgery are improving, octogenarians have a higher procedure-related mortality and more complications with increased length of stay in ICU. Consequently, careful evaluation of perioperative risk seems necessary. The aims of our study were to assess and compare the performances of EuroSCORE and CARE score in the prediction of perioperative mortality among octogenarians undergoing aortic valve replacement for aortic stenosis and to compare these predictive performances with those obtained in younger patients. This retrospective study included all consecutive patients undergoing cardiac surgery in our institution between November 2005 and December 2007. For each patient, risk assessment for mortality was performed using logistic EuroSCORE, additive EuroSCORE and CARE score. The main outcome measure was early postoperative mortality. Predictive performances of these scores were assessed by calibration and discrimination using goodness-of-fit test and area under the receiver operating characteristic curve, respectively. During this 2-year period, we studied 2117 patients, among whom 134/211 octogenarians and 335/1906 nonoctogenarians underwent an aortic valve replacement for aortic stenosis. When considering patients with aortic stenosis, discrimination was poor in octogenarians and the difference from nonoctogenarians was significant for each score (0.58, 0.59 and 0.56 vs. 0.82, 0.81 and 0.77 for additive EuroSCORE, logistic EuroSCORE and CARE score in octogenarians and nonoctogenarians, respectively, P < 0.05). Moreover, in the whole cohort, logistic EuroSCORE significantly overestimated mortality among octogenarians. Predictive performances of these scores are poor in octogenarians undergoing cardiac surgery, especially aortic valve replacement. Risk assessment and therapeutic decisions in octogenarians should not be made with these scoring systems alone.

A threshold-free summary index of prediction accuracy for censored time to event data.

PubMed

Yuan, Yan; Zhou, Qian M; Li, Bingying; Cai, Hengrui; Chow, Eric J; Armstrong, Gregory T

2018-05-10

Prediction performance of a risk scoring system needs to be carefully assessed before its adoption in clinical practice. Clinical preventive care often uses risk scores to screen asymptomatic population. The primary clinical interest is to predict the risk of having an event by a prespecified future time t 0 . Accuracy measures such as positive predictive values have been recommended for evaluating the predictive performance. However, for commonly used continuous or ordinal risk score systems, these measures require a subjective cutoff threshold value that dichotomizes the risk scores. The need for a cutoff value created barriers for practitioners and researchers. In this paper, we propose a threshold-free summary index of positive predictive values that accommodates time-dependent event status and competing risks. We develop a nonparametric estimator and provide an inference procedure for comparing this summary measure between 2 risk scores for censored time to event data. We conduct a simulation study to examine the finite-sample performance of the proposed estimation and inference procedures. Lastly, we illustrate the use of this measure on a real data example, comparing 2 risk score systems for predicting heart failure in childhood cancer survivors. Copyright © 2018 John Wiley & Sons, Ltd.

Performance on the adult rheumatology in-training examination and relationship to outcomes on the rheumatology certification examination.

PubMed

Lohr, Kristine M; Clauser, Amanda; Hess, Brian J; Gelber, Allan C; Valeriano-Marcet, Joanne; Lipner, Rebecca S; Haist, Steven A; Hawley, Janine L; Zirkle, Sarah; Bolster, Marcy B

2015-11-01

The American College of Rheumatology (ACR) Adult Rheumatology In-Training Examination (ITE) is a feedback tool designed to identify strengths and weaknesses in the content knowledge of individual fellows-in-training and the training program curricula. We determined whether scores on the ACR ITE, as well as scores on other major standardized medical examinations and competency-based ratings, could be used to predict performance on the American Board of Internal Medicine (ABIM) Rheumatology Certification Examination. Between 2008 and 2012, 629 second-year fellows took the ACR ITE. Bivariate correlation analyses of assessment scores and multiple linear regression analyses were used to determine whether ABIM Rheumatology Certification Examination scores could be predicted on the basis of ACR ITE scores, United States Medical Licensing Examination scores, ABIM Internal Medicine Certification Examination scores, fellowship directors' ratings of overall clinical competency, and demographic variables. Logistic regression was used to evaluate whether these assessments were predictive of a passing outcome on the Rheumatology Certification Examination. In the initial linear model, the strongest predictors of the Rheumatology Certification Examination score were the second-year fellows' ACR ITE scores (β = 0.438) and ABIM Internal Medicine Certification Examination scores (β = 0.273). Using a stepwise model, the strongest predictors of higher scores on the Rheumatology Certification Examination were second-year fellows' ACR ITE scores (β = 0.449) and ABIM Internal Medicine Certification Examination scores (β = 0.276). Based on the findings of logistic regression analysis, ACR ITE performance was predictive of a pass/fail outcome on the Rheumatology Certification Examination (odds ratio 1.016 [95% confidence interval 1.011-1.021]). The predictive value of the ACR ITE score with regard to predicting performance on the Rheumatology Certification Examination supports use of the Adult Rheumatology ITE as a valid feedback tool during fellowship training. © 2015, American College of Rheumatology.

A real-time prediction model for post-irradiation malignant cervical lymph nodes.

PubMed

Lo, W-C; Cheng, P-W; Shueng, P-W; Hsieh, C-H; Chang, Y-L; Liao, L-J

2018-04-01

To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation. One-hundred forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine-needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model. A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (P < .05). A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation. © 2017 John Wiley & Sons Ltd.

Bayley-III motor scale and neurological examination at 2 years do not predict motor skills at 4.5 years.

PubMed

Burakevych, Nataliia; Mckinlay, Christopher Joel Dorman; Alsweiler, Jane Marie; Wouldes, Trecia Ann; Harding, Jane Elizabeth

2017-02-01

To determine whether Bayley Scales of Infant and Toddler Development (3rd edition) (Bayley-III) motor scores and neurological examination at 2 years corrected age predict motor difficulties at 4.5 years corrected age. A prospective cohort study of children born at risk of neonatal hypoglycaemia in Waikato Hospital, Hamilton, New Zealand. Assessment at 2 years was performed using the Bayley-III motor scale and neurological examination, and at 4.5 years using the Movement Assessment Battery for Children (2nd edition) (MABC-2). Of 333 children, 8 (2%) had Bayley-III motor scores below 85, and 50 (15%) had minor deficits on neurological assessment at 2 years; 89 (27%) scored less than or equal to the 15th centile, and 54 (16%) less than or equal to the 5th centile on MABC-2 at 4.5 years. Motor score, fine and gross motor subtest scores, and neurological assessments at 2 years were poorly predictive of motor difficulties at 4.5 years, explaining 0 to 7% of variance in MABC-2 scores. A Bayley-III motor score below 85 predicted MABC-2 scores less than or equal to the 15th centile with a positive predictive value of 30% and a negative predictive value of 74% (7% sensitivity and 94% specificity). Bayley-III motor scale and neurological examination at 2 years were poorly predictive of motor difficulties at 4.5 years. © 2016 Mac Keith Press.

Bayley-III motor scale and neurological examination at 2 years do not predict motor skills at 4.5 years

PubMed Central

Burakevych, Nataliia; Mckinlay, Christopher Joel Dorman; Alsweiler, Jane Marie; Wouldes, Trecia An; Harding, Jane Elizabeth

2016-01-01

Aim To determine whether Bayley Scales of Infant and Toddler Development (3rd edition) (Bayley-III) motor scores and neurological examination at 2 years' corrected age predict motor difficulties at 4.5 years' corrected age. Method A prospective cohort study of children born at risk of neonatal hypoglycaemia in Waikato Hospital, Hamilton, New Zealand. Assessment at 2 years was performed using the Bayley-III motor scale and neurological examination, and at 4.5 years using the Movement Assessment Battery for Children (2nd edition) (MABC-2). Results Of 333 children, 8 (2%) had Bayley-III motor scores below 85, and 50 (15%) had minor deficits on neurological assessment at 2 years; 89 (27%) scored less than or equal to the 15th centile, and 54 (16%) less than or equal to the 5th centile on MABC-2 at 4.5 years. Motor score, fine and gross motor subtest scores, and neurological assessments at 2 years were poorly predictive of motor difficulties at 4.5 years, explaining 0 to 7% of variance in MABC-2 scores. A Bayley-III motor score below 85 predicted MABC-2 scores less than or equal to the 15th centile with a positive predictive value of 30% and a negative predictive value of 74% (7% sensitivity and 94% specificity). Interpretation Bayley-III motor scale and neurological examination at 2 years were poorly predictive of motor difficulties at 4.5 years. PMID:27543144

New scoring system combining the FIB-4 index and cytokeratin-18 fragments for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Saibara, Toshiji; Ono, Masafumi; Kage, Masayoshi

To establish a new scoring system as a noninvasive tool for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). A total of 170 patients histologically diagnosed with nonalcoholic steatohepatitis (NASH) (n = 130) or nonalcoholic fatty liver (NAFL) (n = 40) were enrolled. We analyzed receiver operating characteristic (ROC) curves and performed multivariate analysis to predict steatohepatitis and liver fibrosis. Multivariate analysis showed that cytokeratin-18 fragment (CK18-F) levels (≥278 U/L) (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.42-14.00; p = 0.010) and the FIB-4 index (≥1.46) (OR, 4.54; 95% CI, 1.93-29.50; p = 0.004) were independently associated with prediction of NASH. We then established a new scoring system (named the FIC-22 score) for predicting NASH using CK18-F levels and FIB-4 index. The areas under the ROC curve (AUROCs) of the FIC-22 score and NAFIC score were 0.82 (95% CI, 0.75-0.89) and 0.71 (95% CI, 0.62-0.78) (p = 0.044). Additionally, the AUROC of the FIC-22 score for predicting the presence of fibrosis (F ≥ 1) was 0.78 (95% CI, 0.70-0.85). In patients with NAFLD, the FIC-22 score had high predictive accuracy not only for steatohepatitis but also for the presence of liver fibrosis.

Prediction of new-onset atrial fibrillation after first-ever ischemic stroke: A comparison of CHADS2, CHA2DS2-VASc and HATCH scores and the added value of stroke severity.

PubMed

Hsieh, Cheng-Yang; Lee, Cheng-Han; Wu, Darren Philbert; Sung, Sheng-Feng

2018-05-01

Early detection of atrial fibrillation after stroke is important for secondary prevention in stroke patients without known atrial fibrillation (AF). We aimed to compare the performance of CHADS 2 , CHA 2 DS 2 -VASc and HATCH scores in predicting AF detected after stroke (AFDAS) and to test whether adding stroke severity to the risk scores improves predictive performance. Adult patients with first ischemic stroke event but without a prior history of AF were retrieved from a nationwide population-based database. We compared C-statistics of CHADS 2 , CHA 2 DS 2 -VASc and HATCH scores for predicting the occurrence of AFDAS during stroke admission (cohort I) and during follow-up after hospital discharge (cohort II). The added value of stroke severity to prediction models was evaluated using C-statistics, net reclassification improvement, and integrated discrimination improvement. Cohort I comprised 13,878 patients and cohort II comprised 12,567 patients. Among them, 806 (5.8%) and 657 (5.2%) were diagnosed with AF, respectively. The CHADS 2 score had the lowest C-statistics (0.558 in cohort I and 0.597 in cohort II), whereas the CHA 2 DS 2 -VASc score had comparable C-statistics (0.603 and 0.644) to the HATCH score (0.612 and 0.653) in predicting AFDAS. Adding stroke severity to each of the three risk scores significantly increased the model performance. In stroke patients without known AF, all three risk scores predicted AFDAS during admission and follow-up, but with suboptimal discrimination. Adding stroke severity improved their predictive abilities. These risk scores, when combined with stroke severity, may help prioritize patients for continuous cardiac monitoring in daily practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

Severity of specific language impairment predicts delayed development in number skills

PubMed Central

Durkin, Kevin; Mok, Pearl L. H.; Conti-Ramsden, Gina

2013-01-01

The extent to which mathematical development is dependent upon language is controversial. This longitudinal study investigates the role of language ability in children's development of number skills. Participants were 229 children with specific language impairment (SLI) who were assessed initially at age 7 and again 1 year later. All participants completed measures of psycholinguistic development (expressive and receptive), performance IQ, and the Basic Number Skills subtest of the British Ability Scales. Number skills data for this sample were compared with normative population data. Consistent with predictions that language impairment would impact on numerical development, average standard scores were more than 1 SD below the population mean at both ages. Although the children showed improvements in raw scores at the second wave of the study, the discrepancy between their scores and the population data nonetheless increased over time. Regression analyses showed that, after controlling for the effect of PIQ, language skills explained an additional 19 and 17% of the variance in number skills for ages 7 and 8, respectively. Furthermore, logistic regression analyses revealed that less improvement in the child's language ability over the course of the year was associated with a greater odds of a drop in performance in basic number skills from 7 to 8 years. The results are discussed in relation to the interaction of linguistic and cognitive factors in numerical development and the implications for mathematical education. PMID:24027548

The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants.

PubMed

Wong, Martin C S; Ching, Jessica Y L; Ng, Simpson; Lam, Thomas Y T; Luk, Arthur K C; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

2016-02-03

We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50-70 years in a colonoscopy screening programme(2008-2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56-0.65, with sensitivities ranging from 0.04-0.44 and specificities from 0.74-0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58-0.72). The NNS (12-19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed.

Should predictive scores based on vital signs be used in the same way as those based on laboratory data? A hypothesis generating retrospective evaluation of in-hospital mortality by four different scoring systems.

PubMed

Kellett, John; Murray, Alan

2016-05-01

few studies have compared the discrimination of predictive scores of in-hospital mortality that used vital signs with those using laboratory results in different patient populations. a hypothesis generating retrospective observational cohort study. A score that only used vital signs was compared with three other scores that used laboratory changes in 44,985 medical and 20,432 surgical patients. the discrimination of the score based only on vital signs was highest for the prediction of in-hospital death within 24h. In contrast the, albeit lower, discrimination of scores based only on laboratory data remained constant for the prediction of death up to 30 days after hospital admission. Moreover, the discrimination of scores based only on laboratory data was higher in surgical than in medical patients. in acutely ill medical patients a vital sign based score appears to predict mortality within 24h better than scores using laboratory data. This may be because in acutely ill patients vital sign changes indicate how well a patient is responding to a current insult. In contrast, for patients without acute illness laboratory data may be a more valuable indication of the patient's capacity to respond to insults in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Predictive Value of Preoperative Health-Related Quality-of-Life Scores on Postoperative Patient-Reported Outcome Scores in Lumbar Spine Surgery

PubMed Central

Hey, Hwee Weng Dennis; Luo, Nan; Chin, Sze Yung; Lau, Eugene Tze Chun; Wang, Pei; Kumar, Naresh; Lau, Leok-Lim; Ruiz, John Nathaniel; Thambiah, Joseph Shanthakumar; Liu, Ka-Po Gabriel; Wong, Hee-Kit

2017-01-01

Study Design: A single-center, retrospective cohort study. Objective: To predict patient-reported outcomes (PROs) using preoperative health-related quality-of-life (HRQoL) scores by quantifying the correlation between them, so as to aid selection of surgical candidates and preoperative counselling. Methods: All patients who underwent single-level elective lumbar spine surgery over a 2-year period were divided into 3 diagnosis groups: spondylolisthesis, spinal stenosis, and disc herniation. Patient characteristics and health scores (Oswestry Low Back Pain and Disability Index [ODI], EQ-5D, and Short Form-36 version 2 [SF-36v2]) were collected at 6 and 24 months and compared between the 3 diagnosis groups. Multivariate modelling was performed to investigate the predictive value of each parameter, particularly preoperative ODI and EQ-5D, on postoperative ODI and EQ-5D scores for all the patients. Results: ODI and EQ-5D at 6 and 24 months improved significantly for all patients, especially in the disc herniation group, compared to the baseline. The magnitude of improvement in ODI and EQ-5D was predictable using preoperative ODI, EQ-5D, and SF-36v2 Mental Component Score. At 6 months, 1-point baseline ODI predicts for 0.7-point increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for 0.01-point decrease in changed EQ-5D score. At 24 months, 1-point baseline ODI predicts for 1-point increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for 0.009-point decrease in changed EQ-5D. A younger age is shown to be a positive predictor of ODI at 24 months. Conclusions: Poorer baseline health scores predict greater improvement in postoperative PROs at 6 and 24 months after the surgery. HRQoL scores can be used to decide on surgery and in preoperative counselling. PMID:29662746

The Predictive Value of Preoperative Health-Related Quality-of-Life Scores on Postoperative Patient-Reported Outcome Scores in Lumbar Spine Surgery.

PubMed

Hey, Hwee Weng Dennis; Luo, Nan; Chin, Sze Yung; Lau, Eugene Tze Chun; Wang, Pei; Kumar, Naresh; Lau, Leok-Lim; Ruiz, John Nathaniel; Thambiah, Joseph Shanthakumar; Liu, Ka-Po Gabriel; Wong, Hee-Kit

2018-04-01

A single-center, retrospective cohort study. To predict patient-reported outcomes (PROs) using preoperative health-related quality-of-life (HRQoL) scores by quantifying the correlation between them, so as to aid selection of surgical candidates and preoperative counselling. All patients who underwent single-level elective lumbar spine surgery over a 2-year period were divided into 3 diagnosis groups: spondylolisthesis, spinal stenosis, and disc herniation. Patient characteristics and health scores (Oswestry Low Back Pain and Disability Index [ODI], EQ-5D, and Short Form-36 version 2 [SF-36v2]) were collected at 6 and 24 months and compared between the 3 diagnosis groups. Multivariate modelling was performed to investigate the predictive value of each parameter, particularly preoperative ODI and EQ-5D, on postoperative ODI and EQ-5D scores for all the patients. ODI and EQ-5D at 6 and 24 months improved significantly for all patients, especially in the disc herniation group, compared to the baseline. The magnitude of improvement in ODI and EQ-5D was predictable using preoperative ODI, EQ-5D, and SF-36v2 Mental Component Score. At 6 months, 1-point baseline ODI predicts for 0.7-point increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for 0.01-point decrease in changed EQ-5D score. At 24 months, 1-point baseline ODI predicts for 1-point increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for 0.009-point decrease in changed EQ-5D. A younger age is shown to be a positive predictor of ODI at 24 months. Poorer baseline health scores predict greater improvement in postoperative PROs at 6 and 24 months after the surgery. HRQoL scores can be used to decide on surgery and in preoperative counselling.

What grades and achievement tests measure.

PubMed

Borghans, Lex; Golsteyn, Bart H H; Heckman, James J; Humphries, John Eric

2016-11-22

Intelligence quotient (IQ), grades, and scores on achievement tests are widely used as measures of cognition, but the correlations among them are far from perfect. This paper uses a variety of datasets to show that personality and IQ predict grades and scores on achievement tests. Personality is relatively more important in predicting grades than scores on achievement tests. IQ is relatively more important in predicting scores on achievement tests. Personality is generally more predictive than IQ on a variety of important life outcomes. Both grades and achievement tests are substantially better predictors of important life outcomes than IQ. The reason is that both capture personality traits that have independent predictive power beyond that of IQ.

What grades and achievement tests measure

PubMed Central

Borghans, Lex; Golsteyn, Bart H. H.; Heckman, James J.; Humphries, John Eric

2016-01-01

Intelligence quotient (IQ), grades, and scores on achievement tests are widely used as measures of cognition, but the correlations among them are far from perfect. This paper uses a variety of datasets to show that personality and IQ predict grades and scores on achievement tests. Personality is relatively more important in predicting grades than scores on achievement tests. IQ is relatively more important in predicting scores on achievement tests. Personality is generally more predictive than IQ on a variety of important life outcomes. Both grades and achievement tests are substantially better predictors of important life outcomes than IQ. The reason is that both capture personality traits that have independent predictive power beyond that of IQ. PMID:27830648

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

PubMed

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Comparison of Harmless Acute Pancreatitis Score with Ranson's Score in Predicting the Severity of Acute Pancreatitis.

PubMed

Al-Qahtani, Hamad Hadi; Alam, Mohammed Khurshid; Waheed, Muhammad

2017-02-01

To determine the predictability of harmless acute pancreatitis score (HAPS) in determining the severity of acute pancreatitis (AP) and compare it with Ranson's score. Prospective cohort study. King Saud Medical City, Riyadh, Kingdom of Saudi Arabia, between January 2012 and December 2015. All patients admitted with AP at King Saud Medical City, Riyadh, during 2012 - 2015 were studied prospectively. Patients were assessed by HAPS and Ranson's score. Predictability values of the two systems were analysed and compared. Out of 116 patients studied, 104 (89.6%) were HAPS positive and predicted to have mild disease. Pancreatitis was mild in 101 (87%) but severe in 3 (2.6%) patients who scored ≥ 3 Ranson's criteria. Among 12 HAPS negative patients, 10 scored ≥ 3 Ranson's criteria and developed severe pancreatitis while 2 (1.7%) with 2 positive Ranson's criteria developed mild pancreatitis. HAPS correctly predicted the disease severity in 101 (87%) patients, a sensitivity of 98% specificity of 77% and accuracy of 96%. Ranson's system predicted correctly in all but took 48 hours for assessment. Statistical analysis showed moderate agreement (Kappa = 0.776, p < 0.001), and positive relation (rs = 0.777, p < 0.001) between the two scores. HAPS is effective in rapid identification of patient who will run non-severe course of AP. Assessment can be completed within one hour from presentation. Ranson's score, although more accurate, takes 48 hours to complete.

Predictive Value of Glasgow Coma Score and Full Outline of Unresponsiveness Score on the Outcome of Multiple Trauma Patients.

PubMed

Baratloo, Alireza; Shokravi, Masumeh; Safari, Saeed; Aziz, Awat Kamal

2016-03-01

The Full Outline of Unresponsiveness (FOUR) score was developed to compensate for the limitations of Glasgow coma score (GCS) in recent years. This study aimed to assess the predictive value of GCS and FOUR score on the outcome of multiple trauma patients admitted to the emergency department. The present prospective cross-sectional study was conducted on multiple trauma patients admitted to the emergency department. GCS and FOUR scores were evaluated at the time of admission and at the sixth and twelfth hours after admission. Then the receiver operating characteristic (ROC) curve, sensitivity, specificity, as well as positive and negative predictive value of GCS and FOUR score were evaluated to predict patients' outcome. Patients' outcome was divided into discharge with and without a medical injury (motor deficit, coma or death). Finally, 89 patients were studied. Sensitivity and specificity of GCS in predicting adverse outcome (motor deficit, coma or death) were 84.2% and 88.6% at the time of admission, 89.5% and 95.4% at the sixth hour and 89.5% and 91.5% at the twelfth hour, respectively. These values for the FOUR score were 86.9% and 88.4% at the time of admission, 89.5% and 100% at the sixth hour and 89.5% and 94.4% at the twelfth hour, respectively. Findings of this study indicate that the predictive value of FOUR score and GCS on the outcome of multiple trauma patients admitted to the emergency department is similar.

Low-Quality Structural and Interaction Data Improves Binding Affinity Prediction via Random Forest.

PubMed

Li, Hongjian; Leung, Kwong-Sak; Wong, Man-Hon; Ballester, Pedro J

2015-06-12

Docking scoring functions can be used to predict the strength of protein-ligand binding. It is widely believed that training a scoring function with low-quality data is detrimental for its predictive performance. Nevertheless, there is a surprising lack of systematic validation experiments in support of this hypothesis. In this study, we investigated to which extent training a scoring function with data containing low-quality structural and binding data is detrimental for predictive performance. We actually found that low-quality data is not only non-detrimental, but beneficial for the predictive performance of machine-learning scoring functions, though the improvement is less important than that coming from high-quality data. Furthermore, we observed that classical scoring functions are not able to effectively exploit data beyond an early threshold, regardless of its quality. This demonstrates that exploiting a larger data volume is more important for the performance of machine-learning scoring functions than restricting to a smaller set of higher data quality.

The mortality risk score and the ADG score: two points-based scoring systems for the Johns Hopkins aggregated diagnosis groups to predict mortality in a general adult population cohort in Ontario, Canada.

PubMed

Austin, Peter C; Walraven, Carl van

2011-10-01

Logistic regression models that incorporated age, sex, and indicator variables for the Johns Hopkins' Aggregated Diagnosis Groups (ADGs) categories have been shown to accurately predict all-cause mortality in adults. To develop 2 different point-scoring systems using the ADGs. The Mortality Risk Score (MRS) collapses age, sex, and the ADGs to a single summary score that predicts the annual risk of all-cause death in adults. The ADG Score derives weights for the individual ADG diagnosis groups. : Retrospective cohort constructed using population-based administrative data. All 10,498,413 residents of Ontario, Canada, between the age of 20 and 100 years who were alive on their birthday in 2007, participated in this study. Participants were randomly divided into derivation and validation samples. : Death within 1 year. In the derivation cohort, the MRS ranged from -21 to 139 (median value 29, IQR 17 to 44). In the validation group, a logistic regression model with the MRS as the sole predictor significantly predicted the risk of 1-year mortality with a c-statistic of 0.917. A regression model with age, sex, and the ADG Score has similar performance. Both methods accurately predicted the risk of 1-year mortality across the 20 vigintiles of risk. The MRS combined values for a person's age, sex, and the John Hopkins ADGs to accurately predict 1-year mortality in adults. The ADG Score is a weighted score representing the presence or absence of the 32 ADG diagnosis groups. These scores will facilitate health services researchers conducting risk adjustment using administrative health care databases.

The association between the metabolic syndrome and metabolic syndrome score and pulmonary function in non-smoking adults.

PubMed

Yoon, Hyun; Gi, Mi Young; Cha, Ju Ae; Yoo, Chan Uk; Park, Sang Muk

2018-03-01

This study assessed the association of metabolic syndrome and metabolic syndrome score with the predicted forced vital capacity and predicted forced expiratory volume in 1 s (predicted forced expiratory volume in 1 s) values in Korean non-smoking adults. We analysed data obtained from 6684 adults during the 2013-2015 Korean National Health and Nutrition Examination Survey. After adjustment for related variables, metabolic syndrome ( p < 0.001) and metabolic syndrome score ( p < 0.001) were found to be inversely associated with the predicted forced vital capacity and forced expiratory volume in 1 s values. The odds ratios of restrictive pulmonary disease (the predicted forced vital capacity < 80.0% with forced expiratory volume in 1 s/FVC ⩾ 70.0%) by metabolic syndrome score with metabolic syndrome score 0 as a reference group showed no significance for metabolic syndrome score 1 [1.061 (95% confidence interval, 0.755-1.490)] and metabolic syndrome score 2 [1.247 (95% confidence interval, 0.890-1.747)], but showed significant for metabolic syndrome score 3 [1.433 (95% confidence interval, 1.010-2.033)] and metabolic syndrome score ⩾ 4 [1.760 (95% confidence interval, 1.216-2.550)]. In addition, the odds ratio of restrictive pulmonary disease of the metabolic syndrome [1.360 (95% confidence interval, 1.118-1.655)] was significantly higher than those of non-metabolic syndrome. Metabolic syndrome and metabolic syndrome score were inversely associated with the predicted forced vital capacity and forced expiratory volume in 1 s values in Korean non-smoking adults. In addition, metabolic syndrome and metabolic syndrome score were positively associated with the restrictive pulmonary disease.

Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms.

PubMed

Arts, E E A; Popa, C D; Den Broeder, A A; Donders, R; Sandoo, A; Toms, T; Rollefstad, S; Ikdahl, E; Semb, A G; Kitas, G D; Van Riel, P L C M; Fransen, J

2016-04-01

Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this study are to adapt the Systematic COronary Risk Evaluation (SCORE) algorithm with determinants of CVD risk in RA and to assess the accuracy of CVD risk prediction calculated with the adapted SCORE algorithm. Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events. The SCORE algorithm was recalibrated by reweighing included traditional CVD risk factors and adapted by adding other potential predictors of CVD. Predictive performance of the recalibrated and adapted SCORE algorithms was assessed and the adapted SCORE was externally validated. Of the 1016 included patients with RA, 103 patients experienced a CVD event. Discriminatory ability was comparable across the original, recalibrated and adapted SCORE algorithms. The Hosmer-Lemeshow test results indicated that all three algorithms provided poor model fit (p<0.05) for the Nijmegen and external validation cohort. The adapted SCORE algorithm mainly improves CVD risk estimation in non-event cases and does not show a clear advantage in reclassifying patients with RA who develop CVD (event cases) into more appropriate risk groups. This study demonstrates for the first time that adaptations of the SCORE algorithm do not provide sufficient improvement in risk prediction of future CVD in RA to serve as an appropriate alternative to the original SCORE. Risk assessment using the original SCORE algorithm may underestimate CVD risk in patients with RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Predicting failure of hematopoietic stem cell mobilization before it starts: the predicted poor mobilizer (pPM) score.

PubMed

Olivieri, Jacopo; Attolico, Immacolata; Nuccorini, Roberta; Pascale, Sara Pasquina; Chiarucci, Martina; Poiani, Monica; Corradini, Paolo; Farina, Lucia; Gaidano, Gianluca; Nassi, Luca; Sica, Simona; Piccirillo, Nicola; Pioltelli, Pietro Enrico; Martino, Massimo; Moscato, Tiziana; Pini, Massimo; Zallio, Francesco; Ciceri, Fabio; Marktel, Sarah; Mengarelli, Andrea; Musto, Pellegrino; Capria, Saveria; Merli, Francesco; Codeluppi, Katia; Mele, Giuseppe; Lanza, Francesco; Specchia, Giorgina; Pastore, Domenico; Milone, Giuseppe; Saraceni, Francesco; Di Nardo, Elvira; Perseghin, Paolo; Olivieri, Attilio

2018-04-01

Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We developed a new prediction model from multivariate analysis whose score (pPM-score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score included as risk factors: increasing age, diagnosis of NHL, positive bone marrow biopsy or cytopenias before mobilization, previous mobilization failure, priming strategy with G-CSF alone, or without upfront plerixafor. A simplified version of pPM-score was categorized using a cut-off to maximize positive likelihood ratio (15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7% (95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60-80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM before starting mobilization, allowing changes in clinical management, such as choice of alternative priming strategies, to avoid highly likely mobilization failure.

Development and validation of a predictive score for perioperative transfusion in patients with hepatocellular carcinoma undergoing liver resection.

PubMed

Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Wang, Wen-Tao; Yan, Lu-Nan

2015-08-01

Liver resection is a major surgery requiring perioperative blood transfusion. Predicting the need for blood transfusion for patients undergoing liver resection is of great importance. The present study aimed to develop and validate a model for predicting transfusion requirement in HBV-related hepatocellular carcinoma patients undergoing liver resection. A total of 1543 consecutive liver resections were included in the study. Randomly selected sample set of 1080 cases (70% of the study cohort) were used to develop a predictive score for transfusion requirement and the remaining 30% (n=463) was used to validate the score. Based on the preoperative and predictable intraoperative parameters, logistic regression was used to identify risk factors and to create an integer score for the prediction of transfusion requirement. Extrahepatic procedure, major liver resection, hemoglobin level and platelets count were identified as independent predictors for transfusion requirement by logistic regression analysis. A score system integrating these 4 factors was stratified into three groups which could predict the risk of transfusion, with a rate of 11.4%, 24.7% and 57.4% for low, moderate and high risk, respectively. The prediction model appeared accurate with good discriminatory abilities, generating an area under the receiver operating characteristic curve of 0.736 in the development set and 0.709 in the validation set. We have developed and validated an integer-based risk score to predict perioperative transfusion for patients undergoing liver resection in a high-volume surgical center. This score allows identifying patients at a high risk and may alter transfusion practices.

Assessing the Performance of 3 Human Immunodeficiency Virus Incidence Risk Scores in a Cohort of Black and White Men Who Have Sex With Men in the South.

PubMed

Jones, Jeb; Hoenigl, Martin; Siegler, Aaron J; Sullivan, Patrick S; Little, Susan; Rosenberg, Eli

2017-05-01

Risk scores have been developed to identify men at high risk of human immunodeficiency virus (HIV) seroconversion. These scores can be used to more efficiently allocate public health prevention resources, such as pre-exposure prophylaxis. However, the published scores were developed with data sets that comprise predominantly white men who have sex with men (MSM) collected several years prior and recruited from a limited geographic area. Thus, it is unclear how well these scores perform in men of different races or ethnicities or men in different geographic regions. We assessed the predictive ability of 3 published scores to predict HIV seroconversion in a cohort of black and white MSM in Atlanta, GA. Questionnaire data from the baseline study visit were used to derive individual scores for each participant. We assessed the discriminatory ability of each risk score to predict HIV seroconversion over 2 years of follow-up. The predictive ability of each score was low among all MSM and lower among black men compared to white men. Each score had lower sensitivity to predict seroconversion among black MSM compared to white MSM and low area under the curve values for the receiver operating characteristic curve indicating poor discriminatory ability. Reliance on the currently available risk scores will result in misclassification of high proportions of MSM, especially black MSM, in terms of HIV risk, leading to missed opportunities for HIV prevention services.

Predictive accuracy of combined genetic and environmental risk scores.

PubMed

Dudbridge, Frank; Pashayan, Nora; Yang, Jian

2018-02-01

The substantial heritability of most complex diseases suggests that genetic data could provide useful risk prediction. To date the performance of genetic risk scores has fallen short of the potential implied by heritability, but this can be explained by insufficient sample sizes for estimating highly polygenic models. When risk predictors already exist based on environment or lifestyle, two key questions are to what extent can they be improved by adding genetic information, and what is the ultimate potential of combined genetic and environmental risk scores? Here, we extend previous work on the predictive accuracy of polygenic scores to allow for an environmental score that may be correlated with the polygenic score, for example when the environmental factors mediate the genetic risk. We derive common measures of predictive accuracy and improvement as functions of the training sample size, chip heritabilities of disease and environmental score, and genetic correlation between disease and environmental risk factors. We consider simple addition of the two scores and a weighted sum that accounts for their correlation. Using examples from studies of cardiovascular disease and breast cancer, we show that improvements in discrimination are generally small but reasonable degrees of reclassification could be obtained with current sample sizes. Correlation between genetic and environmental scores has only minor effects on numerical results in realistic scenarios. In the longer term, as the accuracy of polygenic scores improves they will come to dominate the predictive accuracy compared to environmental scores. © 2017 WILEY PERIODICALS, INC.

Predictive accuracy of combined genetic and environmental risk scores

PubMed Central

Pashayan, Nora; Yang, Jian

2017-01-01

ABSTRACT The substantial heritability of most complex diseases suggests that genetic data could provide useful risk prediction. To date the performance of genetic risk scores has fallen short of the potential implied by heritability, but this can be explained by insufficient sample sizes for estimating highly polygenic models. When risk predictors already exist based on environment or lifestyle, two key questions are to what extent can they be improved by adding genetic information, and what is the ultimate potential of combined genetic and environmental risk scores? Here, we extend previous work on the predictive accuracy of polygenic scores to allow for an environmental score that may be correlated with the polygenic score, for example when the environmental factors mediate the genetic risk. We derive common measures of predictive accuracy and improvement as functions of the training sample size, chip heritabilities of disease and environmental score, and genetic correlation between disease and environmental risk factors. We consider simple addition of the two scores and a weighted sum that accounts for their correlation. Using examples from studies of cardiovascular disease and breast cancer, we show that improvements in discrimination are generally small but reasonable degrees of reclassification could be obtained with current sample sizes. Correlation between genetic and environmental scores has only minor effects on numerical results in realistic scenarios. In the longer term, as the accuracy of polygenic scores improves they will come to dominate the predictive accuracy compared to environmental scores. PMID:29178508

A stepwise composite echocardiographic score predicts severe pulmonary hypertension in patients with interstitial lung disease.

PubMed

Bax, Simon; Bredy, Charlene; Kempny, Aleksander; Dimopoulos, Konstantinos; Devaraj, Anand; Walsh, Simon; Jacob, Joseph; Nair, Arjun; Kokosi, Maria; Keir, Gregory; Kouranos, Vasileios; George, Peter M; McCabe, Colm; Wilde, Michael; Wells, Athol; Li, Wei; Wort, Stephen John; Price, Laura C

2018-04-01

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used "additional PH signs" where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

A stepwise composite echocardiographic score predicts severe pulmonary hypertension in patients with interstitial lung disease

PubMed Central

Bax, Simon; Bredy, Charlene; Kempny, Aleksander; Dimopoulos, Konstantinos; Devaraj, Anand; Walsh, Simon; Jacob, Joseph; Nair, Arjun; Kokosi, Maria; Keir, Gregory; Kouranos, Vasileios; George, Peter M.; McCabe, Colm; Wilde, Michael; Wells, Athol; Li, Wei; Wort, Stephen John; Price, Laura C.

2018-01-01

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used “additional PH signs” where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD. PMID:29750141

Prediction of destination at discharge from a comprehensive rehabilitation hospital using the home care score

PubMed Central

Matsugi, Akiyoshi; Tani, Keisuke; Yoshioka, Nami; Yamashita, Akira; Mori, Nobuhiko; Oku, Kosuke; Murakami, Yoshikazu; Nomura, Shohei; Tamaru, Yoshiki; Nagano, Kiyoshi

2016-01-01

[Purpose] This study investigated whether it is possible to predict return to home at discharge from a rehabilitation hospital in Japan using the home care score of patients with cerebrovascular or osteoarticular disease and low activities of daily living at admission. [Subjects and Methods] The home care score and functional independent measurement were determined for 226 patients at admission and at discharge from five hospitals, and receiver operating characteristic analyses were conducted. [Results] The home care score cutoff point for the prediction of return to home at admission and at discharge was 11, and the area under the curve was more than 0.8. The area under the curve of the home care score was 0.77 for patients with low activities of daily living and within this group, the probability of return to home was approximately 50%, as predicted by the functional independent measurement. The home care score increased after receiving intervention at a rehabilitation hospital. [Conclusion] The home care score is useful for the prediction of return to home from a rehabilitation hospital, although prediction using the functional independent measurement is difficult for patients with low activities of daily living. Moreover, comprehensive interventions provided by the rehabilitation hospitals improve the ability to provide home care of the patient’s family, which is assessed by the home care score. PMID:27821925

A comparison of pre ICU admission SIRS, EWS and q SOFA scores for predicting mortality and length of stay in ICU.

PubMed

Siddiqui, Shahla; Chua, Maureen; Kumaresh, Venkatesan; Choo, Robin

2017-10-01

The 2015 sepsis definitions suggest using the quick SOFA score for risk stratification of sepsis patients among other changes in sepsis definition. Our aim was to validate the q sofa score for diagnosing sepsis and comparing it to traditional scores of pre ICU admission sepsis outcome prediction such as EWS and SIRS in our setting in order to predict mortality and length of stay. This was a retrospective cohort study. We retrospectively calculated the q sofa, SIRS and EWS scores of all ICU patients admitted with the diagnosis of sepsis at our center in 2015. This was analysed using STATA 12. Logistic regression and ROC curves were used for analysis in addition to descriptive analysis. 58 patients were included in the study. Based on our one year results we have shown that although q SOFA is more sensitive in predicting LOS in ICU of sepsis patients, the EWS score is more sensitive and specific in predicting mortality in the ICU of such patients when compared to q SOFA and SIRS scores. In conclusion, we find that in our setting, EWS is better than SIRS and q SOFA for predicting mortality and perhaps length of stay as well. The q Sofa score remains validated for diagnosis of sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

A Study of the Predictability of Praxis I Examination Scores from ACT Scores and Teacher Education Program Prerequisite Courses

ERIC Educational Resources Information Center

Henderson, Allen R.

2013-01-01

This study investigated the relationship between student enrollment in certain college courses and Praxis I scores. Specifically, the study examined the predictive nature of the relationships between students' grades in college algebra, their freshman English course of choice, their ACT scores, and their Praxis I scores. The subjects consisted of…

An exploration of the perceptions, developmental reasoning levels, differences in learning processes, and academic achievement levels of students in introductory college microbiology

NASA Astrophysics Data System (ADS)

Poole, Barbara Ann Matherly

1997-11-01

This study explored the relationship between the grades students earned in introductory college microbiology and American College Testing scores, sex, race, age, GED or high school diploma, full-time or part-time student status, developmental reasoning levels, memory tactics, and expected achievement. The study also explored student perceptions at the beginning and the end of the microbiology courses for science preparation, expected achievement, relevancy of microbiology, and expectations for the course. Archival records for 121 freshman level and 119 sophomore level microbiology students were accessed to obtain final grades, ACT scores, sex, race, age, GED or high school diploma and full-time or part-time status. The same information was obtained for the 113 freshman level and the 85 sophomore level students who participated in the study. The study groups were given the Group Assessment of Logical Thinking to assess their level of formal reasoning ability, the Inventory of Learning Processes-Revised to assess three memory techniques, an initial perception survey, and an exit perception survey. Academic achievement in microbiology could not be predicted using composites of the predictor variables. There were significant relationships between the GALT scores and the predicted grades with both the freshman and the sophomore final grades. The Self-Efficacy Fact Retention scores and the Literal Memorization scores had significant relationships to the final grades of the freshmen but not the sophomores. There was not a significant relationship between the Deep Semantic scores and the final grades in either group. Students indicated that high school science had given them only a medium to low level of preparation for college microbiology. The sophomores felt that previous college science classes had given them a much better preparation for microbiology than did the freshmen students. Both groups expressed the importance of the laboratory experience to the understanding of science and also the relevancy of microbiology both to their chosen professions and to their own personal lives.

Hematoma Shape, Hematoma Size, Glasgow Coma Scale Score and ICH Score: Which Predicts the 30-Day Mortality Better for Intracerebral Hematoma?

PubMed Central

Wang, Chih-Wei; Liu, Yi-Jui; Lee, Yi-Hsiung; Hueng, Dueng-Yuan; Fan, Hueng-Chuen; Yang, Fu-Chi; Hsueh, Chun-Jen; Kao, Hung-Wen; Juan, Chun-Jung; Hsu, Hsian-He

2014-01-01

Purpose To investigate the performance of hematoma shape, hematoma size, Glasgow coma scale (GCS) score, and intracerebral hematoma (ICH) score in predicting the 30-day mortality for ICH patients. To examine the influence of the estimation error of hematoma size on the prediction of 30-day mortality. Materials and Methods This retrospective study, approved by a local institutional review board with written informed consent waived, recruited 106 patients diagnosed as ICH by non-enhanced computed tomography study. The hemorrhagic shape, hematoma size measured by computer-assisted volumetric analysis (CAVA) and estimated by ABC/2 formula, ICH score and GCS score was examined. The predicting performance of 30-day mortality of the aforementioned variables was evaluated. Statistical analysis was performed using Kolmogorov-Smirnov tests, paired t test, nonparametric test, linear regression analysis, and binary logistic regression. The receiver operating characteristics curves were plotted and areas under curve (AUC) were calculated for 30-day mortality. A P value less than 0.05 was considered as statistically significant. Results The overall 30-day mortality rate was 15.1% of ICH patients. The hematoma shape, hematoma size, ICH score, and GCS score all significantly predict the 30-day mortality for ICH patients, with an AUC of 0.692 (P = 0.0018), 0.715 (P = 0.0008) (by ABC/2) to 0.738 (P = 0.0002) (by CAVA), 0.877 (P<0.0001) (by ABC/2) to 0.882 (P<0.0001) (by CAVA), and 0.912 (P<0.0001), respectively. Conclusion Our study shows that hematoma shape, hematoma size, ICH scores and GCS score all significantly predict the 30-day mortality in an increasing order of AUC. The effect of overestimation of hematoma size by ABC/2 formula in predicting the 30-day mortality could be remedied by using ICH score. PMID:25029592

Variceal bleeding in cirrhotic patients: What is the best prognostic score?

PubMed

Mohammad, Asmaa N; Morsy, Khairy H; Ali, Moustafa A

2016-09-01

To find the most accurate, suitable, and applicable scoring system for the prediction of outcome in cirrhotic patients with bleeding varices. A prospective study was conducted comprising 120 cirrhotic patients with acute variceal bleeding who were admitted to Tropical Medicine and Gastroenterology Department in Sohag University Hospital, over a 1-year period (1/2015 to 1/2016). The clinical, laboratory, and endoscopic parameters were studied. Child-Turcotte-Pugh (CTP) classification score, Model for end-stage liver disease (MELD) score, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, and AIMS65 score were calculated for all patients. Univariate and multivariate analyses were performed for all the measured parameters and scores. Of the 120 patients (92 male) admitted during the study period, eight patients (6.67%) died in the hospital. Advanced age, the presence of encephalopathy, rebleeding, and higher serum bilirubin were independent factors associated with higher hospital mortality. The largest area under the receiver operator curve (AUROC) was obtained for the AIMS65 score and SOFA score, followed by the MELD score and APACHEII score, then CTP score, all of which achieved very good performance (AUROC>0.8). AIMS65 score showed the best sensitivity, specificity, and negative and positive predictive values. Although the AIMS65 score was not significantly different from the MELD, SOFA, and APACHEII scores, it was the optimum among them in terms of the prediction of mortality. AIMS65 score is the best simple and applicable scoring system for independently predicting mortality in cirrhotic patients with acute variceal bleeding.

Object-oriented regression for building predictive models with high dimensional omics data from translational studies.

PubMed

Zhao, Lue Ping; Bolouri, Hamid

2016-04-01

Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and has made the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient's similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient's HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (P-value=0.015). Copyright © 2016 Elsevier Inc. All rights reserved.

Object-Oriented Regression for Building Predictive Models with High Dimensional Omics Data from Translational Studies

PubMed Central

Zhao, Lue Ping; Bolouri, Hamid

2016-01-01

Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and to make the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient’s similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient’s HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (p=0.015). PMID:26972839

Long-term bleeding risk prediction in 'real world' patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores. The Murcia Atrial Fibrillation Project.

PubMed

Esteve-Pastor, María Asunción; Rivera-Caravaca, José Miguel; Roldan, Vanessa; Vicente, Vicente; Valdés, Mariano; Marín, Francisco; Lip, Gregory Y H

2017-10-05

Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABC-Bleeding score performed better than HAS-BLED score in a clinical trial cohort but has not been externally validated. The aim of this study was to analyze the predictive performance of the ABC-Bleeding score compared to HAS-BLED score in an independent "real-world" anticoagulated AF patients with long-term follow-up. We enrolled 1,120 patients stable on vitamin K antagonist treatment. The HAS-BLED and ABC-Bleeding scores were quantified. Predictive values were compared by c-indexes, IDI, NRI, as well as decision curve analysis (DCA). Median HAS-BLED score was 2 (IQR 2-3) and median ABC-Bleeding was 16.5 (IQR 14.3-18.6). After 6.5 years of follow-up, 207 (2.84 %/year) patients had major bleeding events, of which 65 (0.89 %/year) had intracranial haemorrhage (ICH) and 85 (1.17 %/year) had gastrointestinal bleeding events (GIB). The c-index of HAS-BLED was significantly higher than ABC-Bleeding for major bleeding (0.583 vs 0.518; p=0.025), GIB (0.596 vs 0.519; p=0.017) and for the composite of ICH-GIB (0.593 vs 0.527; p=0.030). NRI showed a significant negative reclassification for major bleeding and for the composite of ICH-GIB with the ABC-Bleeding score compared to HAS-BLED. Using DCAs, the use of HAS-BLED score gave an approximate net benefit of 4 % over the ABC-Bleeding score. In conclusion, in the first "real-world" validation of the ABC-Bleeding score, HAS-BLED performed significantly better than the ABC-Bleeding score in predicting major bleeding, GIB and the composite of GIB and ICH.

The Predictive Validity of the University Student Selection Examination

ERIC Educational Resources Information Center

Karakaya, Ismail; Tavsancil, Ezel

2008-01-01

The main purpose of this study is to investigate the predictive validity of the 2003 University Student Selection Examination (OSS). For this purpose, freshman grade point average (FGPA) in higher education was predicted by raw scores, standard scores, and placement scores (YEP). This study has been conducted on a research group. In this study,…

Beyond Correlations: Usefulness of High School GPA and Test Scores in Making College Admissions Decisions

ERIC Educational Resources Information Center

Sawyer, Richard

2013-01-01

Correlational evidence suggests that high school GPA is better than admission test scores in predicting first-year college GPA, although test scores have incremental predictive validity. The usefulness of a selection variable in making admission decisions depends in part on its predictive validity, but also on institutions' selectivity and…

Relationships of Measurement Error and Prediction Error in Observed-Score Regression

ERIC Educational Resources Information Center

Moses, Tim

2012-01-01

The focus of this paper is assessing the impact of measurement errors on the prediction error of an observed-score regression. Measures are presented and described for decomposing the linear regression's prediction error variance into parts attributable to the true score variance and the error variances of the dependent variable and the predictor…

Maternal attitudinal inflexibility: longitudinal relations with mother-infant disrupted interaction and childhood hostile-aggressive behavior problems.

PubMed

Najmi, Sadia; Bureau, Jean-Francois; Chen, Diyu; Lyons-Ruth, Karlen

2009-12-01

: The Personal Attitude Scale (PAS; Hooley, 2000) is a method that is under development for identifying individuals high in Expressed Emotion based on personality traits of inflexibility, intolerance, and norm-forming. In the current study, the goal was to measure the association between this maternal attitudinal inflexibility, early hostile or disrupted mother-infant interactions, and hostile-aggressive behavior problems in the child. In a prospective longitudinal study of 76 low-income mothers and their infants, it was predicted that maternal PAS scores, assessed at child age 20, would be related to difficulties in early observed mother-infant interaction and to hostile-aggressive behavioral difficulties in the child. Results indicated that maternal difficulties in interacting with the infant in the laboratory were associated with maternal PAS scores assessed 20 years later. Hostile-aggressive behavior problems in the child at age five were also predictive of PAS scores of mothers. However, contrary to prediction, these behavior problems did not mediate the association between mother-infant interaction difficulties and maternal PAS scores, indicating that the child's hostile-aggressive behavior problems did not produce the link between quality of early interaction and later maternal attitudinal inflexibility. The current results validate the PAS against observable mother-child interactions and child hostile-aggressive behavior problems and indicate the importance of future work investigating the maternal attitudes that are associated with, and may potentially precede, parent-infant interactive difficulties. These findings regarding the inflexible attitudes of mothers whose interactions with their infants are also disrupted have important clinical implications. First, once the stability of the PAS has been established, this measure may offer a valuable screening tool for the prenatal identification of parents at risk for difficult interactions with their children. Second, it suggests routes for more cognitive interventions around helping less flexible parents shift perspectives to better take account of their child's outlooks and needs.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

PubMed

Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G

2016-05-01

We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Predictive Value of the Sequential Organ Failure Assessment Score for Mortality in a Contemporary Cardiac Intensive Care Unit Population.

PubMed

Jentzer, Jacob C; Bennett, Courtney; Wiley, Brandon M; Murphree, Dennis H; Keegan, Mark T; Gajic, Ognjen; Wright, R Scott; Barsness, Gregory W

2018-03-10

Optimal methods of mortality risk stratification in patients in the cardiac intensive care unit (CICU) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in a large cohort of unselected patients in the CICU. Adult patients admitted to the CICU from January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed. SOFA scores were calculated daily, and Acute Physiology and Chronic Health Evaluation (APACHE)-III and APACHE-IV scores were calculated on CICU day 1. Discrimination of hospital mortality was assessed using area under the receiver-operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all-cause hospital mortality was 9.0%. Day 1 SOFA score predicted hospital mortality, with an area under the receiver-operator characteristic curve value of 0.83; area under the receiver-operator characteristic curve values were similar for the APACHE-III score, and APACHE-IV predicted mortality ( P >0.05). Mean and maximum SOFA scores over multiple CICU days had greater discrimination for hospital mortality ( P <0.01). Patients with an increasing SOFA score from day 1 and day 2 had higher mortality. Patients with day 1 SOFA score <2 were at low risk of mortality. Increasing tertiles of day 1 SOFA score predicted higher long-term mortality ( P <0.001 by log-rank test). The day 1 SOFA score has good discrimination for short-term mortality in unselected patients in the CICU, which is comparable to APACHE-III and APACHE-IV. Advantages of the SOFA score over APACHE include simplicity, improved discrimination using serial scores, and prediction of long-term mortality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

PubMed

Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

2017-12-31

To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome

PubMed Central

Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

2017-01-01

Aim To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). Methods This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). Results The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC = 0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC = 0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC = 0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC = 0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC = 0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC = 0.88; 95% CI 1.018-1.072) and on discharge (AUC = 0.78; 95% CI 1.000-1.058). Conclusions In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR. PMID:29308832

Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.

PubMed

Ayva, Sebnem Kupana; Karabulut, Ayse Anil; Akatli, Ayşe Nur; Atasoy, Pinar; Bozdogan, Onder

2013-10-01

Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC. Copyright © 2013 Elsevier GmbH. All rights reserved.

A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding.

PubMed

Tammaro, Leonardo; Buda, Andrea; Di Paolo, Maria Carla; Zullo, Angelo; Hassan, Cesare; Riccio, Elisabetta; Vassallo, Roberto; Caserta, Luigi; Anderloni, Andrea; Natali, Alessandro

2014-09-01

Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. Overall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p=0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p=0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p=0.3). The T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The evaluation of acute physiology and chronic health evaluation II score, poisoning severity score, sequential organ failure assessment score combine with lactate to assess the prognosis of the patients with acute organophosphate pesticide poisoning.

PubMed

Yuan, Shaoxin; Gao, Yusong; Ji, Wenqing; Song, Junshuai; Mei, Xue

2018-05-01

The aim of this study was to assess the ability of acute physiology and chronic health evaluation II (APACHE II) score, poisoning severity score (PSS) as well as sequential organ failure assessment (SOFA) score combining with lactate (Lac) to predict mortality in the Emergency Department (ED) patients who were poisoned with organophosphate.A retrospective review of 59 stands-compliant patients was carried out. Receiver operating characteristic (ROC) curves were constructed based on the APACHE II score, PSS, SOFA score with or without Lac, respectively, and the areas under the ROC curve (AUCs) were determined to assess predictive value. According to SOFA-Lac (a combination of SOFA and Lac) classification standard, acute organophosphate pesticide poisoning (AOPP) patients were divided into low-risk and high-risk groups. Then mortality rates were compared between risk levels.Between survivors and non-survivors, there were significant differences in the APACHE II score, PSS, SOFA score, and Lac (all P < .05). The AUCs of the APACHE II score, PSS, and SOFA score were 0.876, 0.811, and 0.837, respectively. However, after combining with Lac, the AUCs were 0.922, 0.878, and 0.956, respectively. According to SOFA-Lac, the mortality of high-risk group was significantly higher than low-risk group (P < .05) and the patients of the non-survival group were all at high risk.These data suggest the APACHE II score, PSS, SOFA score can all predict the prognosis of AOPP patients. For its simplicity and objectivity, the SOFA score is a superior predictor. Lac significantly improved the predictive abilities of the 3 scoring systems, especially for the SOFA score. The SOFA-Lac system effectively distinguished the high-risk group from the low-risk group. Therefore, the SOFA-Lac system is significantly better at predicting mortality in AOPP patients.

Glasgow Coma Scale score, mortality, and functional outcome in head-injured patients.

PubMed

Udekwu, Pascal; Kromhout-Schiro, Sharon; Vaslef, Steven; Baker, Christopher; Oller, Dale

2004-05-01

Preresuscitation Glasgow Coma Scale (P-GCS) score is frequently obtained in injured patients and incorporated into mortality prediction. Data on functional outcome in head injury is sparse. A large group of patients with head injuries was analyzed to assess relationships between P-GCS score, mortality, and functional outcome as measured by the Functional Independence Measure (FIM). Records for patients with International Classification of Diseases, Ninth Revision diagnosis codes indicating head injury in a statewide trauma registry between 1994 and 2002 were selected. P-GCS score, mortality, and FIM score at hospital discharge were integrated and analyzed. Of 138,750 patients, 22,924 patients were used for the mortality study and 7,150 patients for the FIM study. A good correlation exists between P-GCS score and FIM, as determined by rank correlation coefficients, whereas mortality falls steeply between a P-GCS score of 3 and a P-GCS score of 7 followed by a shallow fall. Although P-GCS score is related to mortality in head-injured patients, its relationship is nonlinear, which casts doubt on its use as a continuous measure or an equivalent set of categorical measures incorporated into outcome prediction models. The average FIM scores indicate substantial likelihood of good outcomes in survivors with low P-GCS scores, further complicating the use of the P-GCS score in the prediction of poor outcome at the time of initial patient evaluation. Although the P-GCS score is related to functional outcome as measured by the FIM score and mortality in head injury, current mortality prediction models may need to be modified to account for the nonlinear relationship between P-GCS score and mortality. The P-GCS score is not a good clinical tool for outcome prediction in individual head-injured patients, given the variability in mortality rates and functional outcomes at all scores.

Features analysis for identification of date and party hubs in protein interaction network of Saccharomyces Cerevisiae.

PubMed

Mirzarezaee, Mitra; Araabi, Babak N; Sadeghi, Mehdi

2010-12-19

It has been understood that biological networks have modular organizations which are the sources of their observed complexity. Analysis of networks and motifs has shown that two types of hubs, party hubs and date hubs, are responsible for this complexity. Party hubs are local coordinators because of their high co-expressions with their partners, whereas date hubs display low co-expressions and are assumed as global connectors. However there is no mutual agreement on these concepts in related literature with different studies reporting their results on different data sets. We investigated whether there is a relation between the biological features of Saccharomyces Cerevisiae's proteins and their roles as non-hubs, intermediately connected, party hubs, and date hubs. We propose a classifier that separates these four classes. We extracted different biological characteristics including amino acid sequences, domain contents, repeated domains, functional categories, biological processes, cellular compartments, disordered regions, and position specific scoring matrix from various sources. Several classifiers are examined and the best feature-sets based on average correct classification rate and correlation coefficients of the results are selected. We show that fusion of five feature-sets including domains, Position Specific Scoring Matrix-400, cellular compartments level one, and composition pairs with two and one gaps provide the best discrimination with an average correct classification rate of 77%. We study a variety of known biological feature-sets of the proteins and show that there is a relation between domains, Position Specific Scoring Matrix-400, cellular compartments level one, composition pairs with two and one gaps of Saccharomyces Cerevisiae's proteins, and their roles in the protein interaction network as non-hubs, intermediately connected, party hubs and date hubs. This study also confirms the possibility of predicting non-hubs, party hubs and date hubs based on their biological features with acceptable accuracy. If such a hypothesis is correct for other species as well, similar methods can be applied to predict the roles of proteins in those species.

Association between Proton Magnetic Resonance Spectroscopy Measurements and CAG Repeat Number in Patients with Spinocerebellar Ataxias 2, 3, or 6

PubMed Central

Wang, Po-Shan; Chen, Hung-Chieh; Wu, Hsiu-Mei; Lirng, Jiing-Feng; Wu, Yu-Te; Soong, Bing-Wen

2012-01-01

The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA. PMID:23094053

Role of the Egami score to predict immunoglobulin resistance in Kawasaki disease among a Western Mediterranean population.

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estíbaliz; Calzada-Hernandez, Joan; Borlan, Sergi; Gimenez-Roca, Clara; Rivera, Josefa

2016-07-01

Kawasaki disease is an acute self-limited systemic vasculitis common in childhood. Intravenous immunoglobulin (IVIG) is an effective treatment, and it reduces the incidence of cardiac complications. Egami score has been validated to identify IVIG non-responder patients in Japanese population, and it has shown high sensitivity and specificity to identify these non-responder patients. Although its effectiveness in Japan, Egami score has shown to be ineffective in non-Japanese populations. The aim of this study was to apply the Egami score in a Western Mediterranean population in Catalonia (Spain). Observational population-based study that includes patients from all Pediatric Units in 33 Catalan hospitals, both public and private management, between January 2004 and March 2014. Sensitivity and specificity for the Egami score was calculated, and a logistic regression analysis of predictors of overall response to IVIG was also developed. Predicting IVIG resistance with a cutoff for Egami score ≥3 obtained 26 % sensitivity and 82 % specificity. Negative predictive value was 85 % and positive predictive value 22 %. This low sensitivity implies that three out of four non-responders will not be identified by the Egami score. Besides, logistic regression models did not found significance for the use of the Egami score to predict IVIG resistance in Catalan population although having an area under the ROC curve of 0.618 (IC 95 % 0.538-0.698, p < 0.001). Although regression models found an area under the ROC curve >0.5 to predict IVIG resistance, the low sensitivity excludes the Egami score as a useful tool to predict IVIG resistance in Catalan population.

Evoked Emotions Predict Food Choice

PubMed Central

Dalenberg, Jelle R.; Gutjar, Swetlana; ter Horst, Gert J.; de Graaf, Kees; Renken, Remco J.; Jager, Gerry

2014-01-01

In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well scores from emotion-profiling methods predict actual food choice and/or consumption. To test this, we proposed to decompose emotion scores into valence and arousal scores using Principal Component Analysis (PCA) and apply Multinomial Logit Models (MLM) to estimate food choice using liking, valence, and arousal as possible predictors. For this analysis, we used an existing data set comprised of liking and food-evoked emotions scores from 123 participants, who rated 7 unlabeled breakfast drinks. Liking scores were measured using a 100-mm visual analogue scale, while food-evoked emotions were measured using 2 existing emotion-profiling methods: a verbal and a non-verbal method (EsSense Profile and PrEmo, respectively). After 7 days, participants were asked to choose 1 breakfast drink from the experiment to consume during breakfast in a simulated restaurant environment. Cross validation showed that we were able to correctly predict individualized food choice (1 out of 7 products) for over 50% of the participants. This number increased to nearly 80% when looking at the top 2 candidates. Model comparisons showed that evoked emotions better predict food choice than perceived liking alone. However, the strongest predictive strength was achieved by the combination of evoked emotions and liking. Furthermore we showed that non-verbal food-evoked emotion scores more accurately predict food choice than verbal food-evoked emotions scores. PMID:25521352

Evoked emotions predict food choice.

PubMed

Dalenberg, Jelle R; Gutjar, Swetlana; Ter Horst, Gert J; de Graaf, Kees; Renken, Remco J; Jager, Gerry

2014-01-01

In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well scores from emotion-profiling methods predict actual food choice and/or consumption. To test this, we proposed to decompose emotion scores into valence and arousal scores using Principal Component Analysis (PCA) and apply Multinomial Logit Models (MLM) to estimate food choice using liking, valence, and arousal as possible predictors. For this analysis, we used an existing data set comprised of liking and food-evoked emotions scores from 123 participants, who rated 7 unlabeled breakfast drinks. Liking scores were measured using a 100-mm visual analogue scale, while food-evoked emotions were measured using 2 existing emotion-profiling methods: a verbal and a non-verbal method (EsSense Profile and PrEmo, respectively). After 7 days, participants were asked to choose 1 breakfast drink from the experiment to consume during breakfast in a simulated restaurant environment. Cross validation showed that we were able to correctly predict individualized food choice (1 out of 7 products) for over 50% of the participants. This number increased to nearly 80% when looking at the top 2 candidates. Model comparisons showed that evoked emotions better predict food choice than perceived liking alone. However, the strongest predictive strength was achieved by the combination of evoked emotions and liking. Furthermore we showed that non-verbal food-evoked emotion scores more accurately predict food choice than verbal food-evoked emotions scores.

An Empiric HIV Risk Scoring Tool to Predict HIV-1 Acquisition in African Women.

PubMed

Balkus, Jennifer E; Brown, Elizabeth; Palanee, Thesla; Nair, Gonasagrie; Gafoor, Zakir; Zhang, Jingyang; Richardson, Barbra A; Chirenje, Zvavahera M; Marrazzo, Jeanne M; Baeten, Jared M

2016-07-01

To develop and validate an HIV risk assessment tool to predict HIV acquisition among African women. Data were analyzed from 3 randomized trials of biomedical HIV prevention interventions among African women (VOICE, HPTN 035, and FEM-PrEP). We implemented standard methods for the development of clinical prediction rules to generate a risk-scoring tool to predict HIV acquisition over the course of 1 year. Performance of the score was assessed through internal and external validations. The final risk score resulting from multivariable modeling included age, married/living with a partner, partner provides financial or material support, partner has other partners, alcohol use, detection of a curable sexually transmitted infection, and herpes simplex virus 2 serostatus. Point values for each factor ranged from 0 to 2, with a maximum possible total score of 11. Scores ≥5 were associated with HIV incidence >5 per 100 person-years and identified 91% of incident HIV infections from among only 64% of women. The area under the curve (AUC) for predictive ability of the score was 0.71 (95% confidence interval [CI]: 0.68 to 0.74), indicating good predictive ability. Risk score performance was generally similar with internal cross-validation (AUC = 0.69; 95% CI: 0.66 to 0.73) and external validation in HPTN 035 (AUC = 0.70; 95% CI: 0.65 to 0.75) and FEM-PrEP (AUC = 0.58; 95% CI: 0.51 to 0.65). A discrete set of characteristics that can be easily assessed in clinical and research settings was predictive of HIV acquisition over 1 year. The use of a validated risk score could improve efficiency of recruitment into HIV prevention research and inform scale-up of HIV prevention strategies in women at highest risk.

Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis Undergoing Non-Hepatic Surgeries

PubMed Central

Hemida, Khalid; Shabana, Sherif Sadek; Said, Hani; Ali-Eldin, Fatma

2016-01-01

Introduction Patients with chronic liver diseases are at great risk for both morbidity and mortality during the post-operative period due to the stress of surgery and the effects of general anaesthesia. Aim The main aim of this study was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post-operative mortality in Egyptian patients with liver cirrhosis undergoing non-hepatic surgery under general anaesthesia. Materials and Methods A total of 60 patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in this study. Sensitivity and specificity of MELD and CTP scores were evaluated for the prediction of post-operative mortality. A total of 20 patients who had no clinical, biochemical or radiological evidence of liver disease were included to serve as a control group. Results The highest sensitivity and specificity for detection of post-operative mortality was detected at a MELD score of 13.5. CTP score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy of 95% for prediction of post-operative mortality. On the other side and at a cut-off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%, and an overall accuracy of 66.6% for prediction of post-operative mortality in patients with HCV- related liver cirrhosis. Conclusion MELD score proved to be more sensitive but less specific than CTP score for prediction of post-operative mortality. CTP and MELD scores may be complementary rather than competitive in predicting post-operative mortality in patients with HCV- related liver cirrhosis. PMID:27891371

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

PubMed

Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

2018-04-01

We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer.

PubMed

Aleskandarany, M A; Green, A R; Ashankyty, I; Elmouna, A; Diez-Rodriguez, M; Nolan, C C; Ellis, I O; Rakha, E A

2016-07-01

In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression hot spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), co-efficient of variation, and correlation co-efficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (P < 0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r = 0.98, P < 0.001). In conclusion, assessment of Ki67 expression using HS scoring method on a full-face BC tissue section can represent the primary tumour growth fraction that is likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.

Student assessment by objective structured examination in a neurology clerkship

PubMed Central

Adesoye, Taiwo; Smith, Sandy; Blood, Angela; Brorson, James R.

2012-01-01

Objectives: We evaluated the reliability and predictive ability of an objective structured clinical examination (OSCE) in the assessment of medical students at the completion of a neurology clerkship. Methods: We analyzed data from 195 third-year medical students who took the OSCE. For each student, the OSCE consisted of 2 standardized patient encounters. The scores obtained from each encounter were compared. Faculty clinical evaluations of each student for 2 clinical inpatient rotations were also compared. Hierarchical regression analysis was applied to test the ability of the averaged OSCE scores to predict standardized written examination scores and composite clinical scores. Results: Students' OSCE scores from the 2 standardized patient encounters were significantly correlated with each other (r = 0.347, p < 0.001), and the scores for all students were normally distributed. In contrast, students' faculty clinical evaluation scores from 2 different clinical inpatient rotations were uncorrelated, and scores were skewed toward the highest ratings. After accounting for clerkship order, better OSCE scores were predictive of better National Board of Medical Examiners standardized examination scores (R2Δ = 0.131, p < 0.001) and of better faculty clinical scores (R2Δ = 0.078, p < 0.001). Conclusions: Student assessment by an OSCE provides a reliable and predictive objective assessment of clinical performance in a neurology clerkship. PMID:22855865

Scoring Coreference Partitions of Predicted Mentions: A Reference Implementation.

PubMed

Pradhan, Sameer; Luo, Xiaoqiang; Recasens, Marta; Hovy, Eduard; Ng, Vincent; Strube, Michael

2014-06-01

The definitions of two coreference scoring metrics- B 3 and CEAF-are underspecified with respect to predicted , as opposed to key (or gold ) mentions. Several variations have been proposed that manipulate either, or both, the key and predicted mentions in order to get a one-to-one mapping. On the other hand, the metric BLANC was, until recently, limited to scoring partitions of key mentions. In this paper, we (i) argue that mention manipulation for scoring predicted mentions is unnecessary, and potentially harmful as it could produce unintuitive results; (ii) illustrate the application of all these measures to scoring predicted mentions; (iii) make available an open-source, thoroughly-tested reference implementation of the main coreference evaluation measures; and (iv) rescore the results of the CoNLL-2011/2012 shared task systems with this implementation. This will help the community accurately measure and compare new end-to-end coreference resolution algorithms.

Purposes and methods of scoring earthquake forecasts

NASA Astrophysics Data System (ADS)

Zhuang, J.

2010-12-01

There are two kinds of purposes in the studies on earthquake prediction or forecasts: one is to give a systematic estimation of earthquake risks in some particular region and period in order to give advice to governments and enterprises for the use of reducing disasters, the other one is to search for reliable precursors that can be used to improve earthquake prediction or forecasts. For the first case, a complete score is necessary, while for the latter case, a partial score, which can be used to evaluate whether the forecasts or predictions have some advantages than a well know model, is necessary. This study reviews different scoring methods for evaluating the performance of earthquake prediction and forecasts. Especially, the gambling scoring method, which is developed recently, shows its capacity in finding good points in an earthquake prediction algorithm or model that are not in a reference model, even if its overall performance is no better than the reference model.

Predictive Value of Different Expressions of Forced Expiratory Volume in 1 Second (FEV1) for Adverse Outcomes in a Cohort of Adults Aged 80 and Older.

PubMed

Hegendörfer, Eralda; Vaes, Bert; Andreeva, Elena; Matheï, Catharina; Van Pottelbergh, Gijs; Degryse, Jean-Marie

2017-02-01

Forced expiratory volume in 1 second (FEV 1 ) is proposed as a marker of healthy ageing and FEV 1 expressions that are independent of reference values have been reported to be better at predicting mortality in older adults. We assess and compare the predictive value of different FEV 1 expressions for mortality, hospitalization, and physical and mental decline in adults aged 80 and older. Population-based, prospective, cohort study. The BELFRAIL study, Belgium. A total of 501 community-dwelling adults aged 80 and older (mean age 84.7 years). Baseline FEV 1 expressed as percent predicted (FEV 1 PP) and z-score (FEV 1 Z) using the Global Lung Function Initiative 2012 reference values; over lowest sex-specific percentile (FEV 1 Q), and height squared (FEV 1 /Ht 2 ) and cubed (FEV 1 /Ht 3 ). Mortality data until 5.1 ± 0.2 years from baseline; hospitalization data until 3.0 ± 0.25 years. Activities of daily living, battery of physical performance tests, Mini-Mental State Examination, and 15-item Geriatric Depression Scale at baseline and after 1.7 ± 0.2 years. Individuals in the lowest quartile of FEV 1 expressions had higher adjusted risk than the rest of study population for all-cause mortality (highest hazard ratio 2.05 [95% Confidence Interval 1.50-2.80] for FEV 1 Q and 2.01 [1.47-2.76] for FEV 1 /Ht 3 ), first hospitalization (highest hazard ratio 1.63 [1.21-2.16] for FEV 1 /Ht 2 and 1.61[1.20-2.16] for FEV 1 /Ht 3 ), mental decline (highest odds ratio 2.80 [1.61-4.89] for FEV 1 Q) and physical decline (only FEV 1 /Ht 3 with odds ratio 1.93 [1.13-3.30]). Based on risk classification improvement measures, FEV 1 /Ht 3 and FEV 1 Q performed better than FEV 1 PP. In a cohort of adults aged 80 and older, FEV 1 expressions that are independent of reference values (FEV 1 /Ht 3 and FEV 1 Q) were better at predicting adverse health outcomes than traditional expressions that depend on reference values, and should be used in further research on FEV 1 and aging. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Increased expression of progesterone receptor membrane component 1 is associated with aggressive phenotype and poor prognosis in ER-positive and negative breast cancer.

PubMed

Ruan, Xiangyan; Zhang, Ying; Mueck, Alfred O; Willibald, Marina; Seeger, Harald; Fehm, Tanja; Brucker, Sara; Neubauer, Hans

2017-02-01

Expression of progesterone receptor membrane component 1 (PGRMC1) has been shown to be higher in breast cancer than normal tissue. We have previously shown that certain progestogens strongly stimulate proliferation of breast cancer cells overexpressing PGRMC1, and therefore hypothesize that PGRMC1 may play a critical role in breast cancer progression. Because little information is available if expression of PGRMC1 is also associated with worse prognosis for breast cancer patients, in this study we investigated the clinicopathologic significance of PGRMC1 expression in breast cancer tissue. Expression of PGRMC1 was analyzed by immunohistochemical staining of primary tumor tissues obtained from 69 breast cancer patients. A labeling score was developed, and results were correlated with tumor size, lymph node metastasis, and clinical outcome. Overexpression of PGRMC1 is correlating with larger tumor size and lymph node metastasis. Kaplan-Meier survival curves indicate that patients with PGRMC1 tumors have poorer disease-free and overall survival independent from the estrogen receptor status than breast cancer patients with PGRMC1 tumors. Our findings suggest that the expression of PGRMC1 might be useful for predicting prognosis in patients with breast cancer.

Personality and mental health treatment: Traits as predictors of presentation, usage, and outcome.

PubMed

Thalmayer, Amber Gayle

2018-03-08

Self-report scores on personality inventories predict important life outcomes, including health and longevity, marital outcomes, career success, and mental health problems, but the ways they predict mental health treatment have not been widely explored. Psychotherapy is sought for diverse problems, but about half of those who begin therapy drop out, and only about half who complete therapy experience lasting improvements. Several authors have argued that understanding how personality traits relate to treatment could lead to better targeted, more successful services. Here self-report scores on Big Five and Big Six personality dimensions are explored as predictors of therapy presentation, usage, and outcomes in a sample of community clinic clients (N = 306). Participants received evidence-based treatments in the context of individual-, couples-, or family-therapy sessions. One measure of initial functioning and three indicators of outcome were used. All personality trait scores except Openness associated with initial psychological functioning. Higher Conscientiousness scores predicted more sessions attended for family therapy but fewer for couples-therapy clients. Higher Honesty-Propriety and Extraversion scores predicted fewer sessions attended for family-therapy clients. Better termination outcome was predicted by higher Conscientiousness scores for family- and higher Extraversion scores for individual-therapy clients. Higher Honesty-Propriety and Neuroticism scores predicted more improvement in psychological functioning in terms of successive Outcome Questionnaire-45 administrations. Taken together, the results provide some support for the role of personality traits in predicting treatment usage and outcome and for the utility of a 6-factor model in this context. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Association of high proliferation marker Ki-67 expression with DCEMR imaging features of breast: a large scale evaluation

NASA Astrophysics Data System (ADS)

Saha, Ashirbani; Harowicz, Michael R.; Grimm, Lars J.; Kim, Connie E.; Ghate, Sujata V.; Walsh, Ruth; Mazurowski, Maciej A.

2018-02-01

One of the methods widely used to measure the proliferative activity of cells in breast cancer patients is the immunohistochemical (IHC) measurement of the percentage of cells stained for nuclear antigen Ki-67. Use of Ki-67 expression as a prognostic marker is still under investigation. However, numerous clinical studies have reported an association between a high Ki-67 and overall survival (OS) and disease free survival (DFS). On the other hand, to offer non-invasive alternative in determining Ki-67 expression, researchers have made recent attempts to study the association of Ki-67 expression with magnetic resonance (MR) imaging features of breast cancer in small cohorts (<30). Here, we present a large scale evaluation of the relationship between imaging features and Ki-67 score as: (a) we used a set of 450 invasive breast cancer patients, (b) we extracted a set of 529 imaging features of shape and enhancement from breast, tumor and fibroglandular tissue of the patients, (c) used a subset of patients as the training set to select features and trained a multivariate logistic regression model to predict high versus low Ki-67 values, and (d) we validated the performance of the trained model in an independent test set using the area-under the receiver operating characteristics (ROC) curve (AUC) of the values predicted. Our model was able to predict high versus low Ki-67 in the test set with an AUC of 0.67 (95% CI: 0.58-0.75, p<1.1e-04). Thus, a moderate strength of association of Ki-67 values and MRextracted imaging features was demonstrated in our experiments.

Assertion Training with Korean College Students: Effects on Self-Expression and Anxiety.

ERIC Educational Resources Information Center

Hong, Kyung-Ja; Cooker, Philip G.

1984-01-01

Examined the effects of assertiveness training on the self-expression skills of 65 Korean college students. Results showed the treatment group scored significantly higher on the College Self Expression Scale than placebo or control groups, and males scored significantly higher than females. (JAC)

Personality Assessment Inventory scores as predictors of misconduct among sex offenders civilly committed as sexually violent predators.

PubMed

Boccaccini, Marcus T; Rufino, Katrina A; Jackson, Rebecca L; Murrie, Daniel C

2013-12-01

We examined the usefulness of scores on the Personality Assessment Inventory (PAI; Morey, 1991) in predicting treatment program violations among 76 sexual offenders civilly committed as sexually violent predators. Scores on the Borderline Features scale (area under the curve [AUC] = .69, p = .005) and Negative Relationships subscale (BOR-N: AUC = .71, p < .001) were the strongest predictors of misconduct, outperforming scores on scales designed to predict poor treatment amenability and antisocial behavior. Incremental validity analyses indicated that BOR scores made a significant contribution to the prediction of misconduct after controlling for scores on measures of overall self-reported distress (e.g., Mean Clinical Elevation, Negative Impression), which were also predictive of program violations. Overall, our findings point to the potential utility of integrating components of treatment for borderline personality disorder into sex offender treatment. (c) 2013 APA, all rights reserved.

Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy.

PubMed

Renard Penna, Raphaele; Cancel-Tassin, Geraldine; Comperat, Eva; Mozer, Pierre; Léon, Priscilla; Varinot, Justine; Roupret, Morgan; Bitker, Marc-Olivier; Lucidarme, Olivier; Cussenot, Olivier

2016-10-01

To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 × 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 × 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics.

An Empirical Investigation of Change in MCAT Scores upon Retest.

ERIC Educational Resources Information Center

Hynes, Kevin; Givner, Nathaniel

1980-01-01

An investigation of Medical College Admission Test (MCAT) retest scores indicates that limited retest improvement may result when initial scores are fairly low or below what might be predicted based on grade point averages. However, when initial scores approach the national, standardized MCAT mean, or are above what might be predicted, significant…

The Predictive Validity of the ABFM's In-Training Examination.

PubMed

O'Neill, Thomas R; Li, Zijia; Peabody, Michael R; Lybarger, Melanie; Royal, Kenneth; Puffer, James C

2015-05-01

Our objective was to examine the predictive validity of the American Board of Family Medicine's (ABFM) In-Training Examination (ITE) with regard to predicting outcomes on the ABFM certification examination. This study used a repeated measures design across three levels of medical training (PGY1--PGY2, PGY2--PGY3, and PGY3--initial certification) with three different cohorts (2010--2011, 2011--2012, and 2012--2013) to examine: (1) how well the residents' ITE scores correlated with their test scores in the following year, (2) what the typical score increase was across training years, and (3) what was the sensitivity, specificity, positive predictive value, and negative predictive value of the PGY3 scores with regard to predicting future results on the MC-FP Examination. ITE scores generally correlate at about .7 with the following year's ITE or with the following year's certification examination. The mean growth from PGY1 to PGY2 was 52 points, from PGY2 to PGY3 was 34 points, and from PGY3 to initial certification was 27 points. The sensitivity, specificity, positive predictive value, and negative predictive value were .91, .47, .96, and .27, respectively. The ITE is a useful predictor of future ITE and initial certification examination performance.

Scoring life insurance applicants' laboratory results, blood pressure and build to predict all-cause mortality risk.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2012-01-01

Evaluate the degree of medium to longer term mortality prediction possible from a scoring system covering all laboratory testing used for life insurance applicants, as well as blood pressure and build measurements. Using the results of testing for life insurance applicants who reported a Social Security number in conjunction with the Social Security Death Master File, the mortality associated with each test result was defined by age and sex. The individual mortality scores for each test were combined for each individual and a composite mortality risk score was developed. This score was then tested against the insurance applicant dataset to evaluate its ability to discriminate risk across age and sex. The composite risk score was highly predictive of all-cause mortality risk in a linear manner from the best to worst quintile of scores in a nearly identical fashion for each sex and decade of age. Laboratory studies, blood pressure and build from life insurance applicants can be used to create scoring that predicts all-cause mortality across age and sex. Such an approach may hold promise for preventative health screening as well.

Bullying among Spanish secondary education students: the role of gender traits, sexism, and homophobia.

PubMed

Carrera-Fernández, María-Victoria; Lameiras-Fernández, María; Rodríguez-Castro, Yolanda; Vallejo-Medina, Pablo

2013-09-01

The aim of the present study was to assess the combined influence of gender stereotypes, sexism, and homophobia on attitudes toward bullying and bullying behavior. A total of 1,500 Spanish adolescents between 12 and 18 years of age (49.3% girls and 50.7% boys) completed a questionnaire that included measures of bullying, attitudes toward bullying, gender-stereotyped personality traits (instrumentality and expressiveness), hostile and benevolent sexism, and attitudes toward gay men and lesbians. First, the findings demonstrated that boys scored significantly higher on all the variables assessed except on benevolent sexism. Two similar models were obtained for both sexes. Benevolent sexism and, in boys, more positive attitudes toward gay men predicted more negative attitudes toward bullying when mediated by more expressive gender traits. An inverse pattern was also observed: Hostile sexism predicted more favorable attitudes toward bullying when mediated by instrumental gender traits. Attitudes toward bullying were highly correlated with bullying behavior. The five-predictor variables (including attitudes toward bullying) explained 58% of the variance of bullying behavior in girls and 37% of such variance in boys.

Identification of differentially expressed small non-coding RNAs in the legume endosymbiont Sinorhizobium meliloti by comparative genomics

PubMed Central

del Val, Coral; Rivas, Elena; Torres-Quesada, Omar; Toro, Nicolás; Jiménez-Zurdo, José I

2007-01-01

Bacterial small non-coding RNAs (sRNAs) are being recognized as novel widespread regulators of gene expression in response to environmental signals. Here, we present the first search for sRNA-encoding genes in the nitrogen-fixing endosymbiont Sinorhizobium meliloti, performed by a genome-wide computational analysis of its intergenic regions. Comparative sequence data from eight related α-proteobacteria were obtained, and the interspecies pairwise alignments were scored with the programs eQRNA and RNAz as complementary predictive tools to identify conserved and stable secondary structures corresponding to putative non-coding RNAs. Northern experiments confirmed that eight of the predicted loci, selected among the original 32 candidates as most probable sRNA genes, expressed small transcripts. This result supports the combined use of eQRNA and RNAz as a robust strategy to identify novel sRNAs in bacteria. Furthermore, seven of the transcripts accumulated differentially in free-living and symbiotic conditions. Experimental mapping of the 5′-ends of the detected transcripts revealed that their encoding genes are organized in autonomous transcription units with recognizable promoter and, in most cases, termination signatures. These findings suggest novel regulatory functions for sRNAs related to the interactions of α-proteobacteria with their eukaryotic hosts. PMID:17971083

Predictive value of the APACHE II, SAPS II, SOFA and GCS scoring systems in patients with severe purulent bacterial meningitis.

PubMed

Pietraszek-Grzywaczewska, Iwona; Bernas, Szymon; Łojko, Piotr; Piechota, Anna; Piechota, Mariusz

2016-01-01

Scoring systems in critical care patients are essential for predicting of the patient outcome and evaluating the therapy. In this study, we determined the value of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Scale (GCS) scoring systems in the prediction of mortality in adult patients admitted to the intensive care unit (ICU) with severe purulent bacterial meningitis. We retrospectively analysed data from 98 adult patients with severe purulent bacterial meningitis who were admitted to the single ICU between March 2006 and September 2015. Univariate logistic regression identified the following risk factors of death in patients with severe purulent bacterial meningitis: APACHE II, SAPS II, SOFA, and GCS scores, and the lengths of ICU stay and hospital stay. The independent risk factors of patient death in multivariate analysis were the SAPS II score, the length of ICU stay and the length of hospital stay. In the prediction of mortality according to the area under the curve, the SAPS II score had the highest accuracy followed by the APACHE II, GCS and SOFA scores. For the prediction of mortality in a patient with severe purulent bacterial meningitis, SAPS II had the highest accuracy.

Predicting Motor Skills from Strengths and Difficulties Questionnaire Scores, Language Ability, and Other Features of New Zealand Children Entering Primary School

ERIC Educational Resources Information Center

Sargisson, Rebecca J.; Powell, Cheniel; Stanley, Peter; de Candole, Rosalind

2014-01-01

The motor and language skills, emotional and behavioural problems of 245 children were measured at school entry. Fine motor scores were significantly predicted by hyperactivity, phonetic awareness, prosocial behaviour, and the presence of medical problems. Gross motor scores were significantly predicted by the presence of medical problems. The…

Does the MCAT predict medical school and PGY-1 performance?

PubMed

Saguil, Aaron; Dong, Ting; Gingerich, Robert J; Swygert, Kimberly; LaRochelle, Jeffrey S; Artino, Anthony R; Cruess, David F; Durning, Steven J

2015-04-01

The Medical College Admissions Test (MCAT) is a high-stakes test required for entry to most U. S. medical schools; admissions committees use this test to predict future accomplishment. Although there is evidence that the MCAT predicts success on multiple choice-based assessments, there is little information on whether the MCAT predicts clinical-based assessments of undergraduate and graduate medical education performance. This study looked at associations between the MCAT and medical school grade point average (GPA), Medical Licensing Examination (USMLE) scores, observed patient care encounters, and residency performance assessments. This study used data collected as part of the Long-Term Career Outcome Study to determine associations between MCAT scores, USMLE Step 1, Step 2 clinical knowledge and clinical skill, and Step 3 scores, Objective Structured Clinical Examination performance, medical school GPA, and PGY-1 program director (PD) assessment of physician performance for students graduating 2010 and 2011. MCAT data were available for all students, and the PGY PD evaluation response rate was 86.2% (N = 340). All permutations of MCAT scores (first, last, highest, average) were weakly associated with GPA, Step 2 clinical knowledge scores, and Step 3 scores. MCAT scores were weakly to moderately associated with Step 1 scores. MCAT scores were not significantly associated with Step 2 clinical skills Integrated Clinical Encounter and Communication and Interpersonal Skills subscores, Objective Structured Clinical Examination performance or PGY-1 PD evaluations. MCAT scores were weakly to moderately associated with assessments that rely on multiple choice testing. The association is somewhat stronger for assessments occurring earlier in medical school, such as USMLE Step 1. The MCAT was not able to predict assessments relying on direct clinical observation, nor was it able to predict PD assessment of PGY-1 performance. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Prediction of gross motor development and independent walking in infants born very preterm using the Test of Infant Motor Performance and the Alberta Infant Motor Scale.

PubMed

Nuysink, Jacqueline; van Haastert, Ingrid C; Eijsermans, Maria J C; Koopman-Esseboom, Corine; Helders, Paul J M; de Vries, Linda S; van der Net, Janjaap

2013-09-01

One objective of a neonatal follow-up program is to examine and predict gross motor outcome of infants born preterm. To assess the concurrent validity of the Test of Infant Motor Performance (TIMP) and the Alberta Infant Motor Scale (AIMS), the ability to predict gross motor outcome around 15 months corrected age (CA), and to explore factors associated with the age of independent walking. 95 infants, born at a gestational age <30 weeks, were assessed around 3, 6 and 15 months CA. At 3 months CA, correlations of raw-scores, Z-scores, and diagnostic agreement between TIMP and AIMS were determined. AIMS-score at 15 months CA and parental-reported walking age were outcome measures for regression analyses. The correlation between TIMP and AIMS raw-scores was 0.82, and between Z-scores 0.71. A cut-off Z-score of -1.0 on the TIMP had 92% diagnostic agreement (κ = 0.67) with an AIMS-score < P10. Neither TIMP- nor AIMS-scores at 3 months CA were associated with the gross motor outcome at 15 months CA. The AIMS-scores at 6 months CA predicted the AIMS-scores at 15 months CA with an explained variance of 19%. Median walking age was 15.7 months CA, with which only the hazard ratio of the AIMS at 6 months CA and ethnicity were significantly associated. Prediction of gross motor development at 15 months CA and independent walking was not possible prior to 6 months CA using the AIMS, with restricted predictive value. Cultural and infant factors seem to influence the onset of independent walking. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of 3D-Jury on CASP7 models.

PubMed

Kaján, László; Rychlewski, Leszek

2007-08-21

3D-Jury, the structure prediction consensus method publicly available in the Meta Server http://meta.bioinfo.pl/, was evaluated using models gathered in the 7th round of the Critical Assessment of Techniques for Protein Structure Prediction (CASP7). 3D-Jury is an automated expert process that generates protein structure meta-predictions from sets of models obtained from partner servers. The performance of 3D-Jury was analysed for three aspects. First, we examined the correlation between the 3D-Jury score and a model quality measure: the number of correctly predicted residues. The 3D-Jury score was shown to correlate significantly with the number of correctly predicted residues, the correlation is good enough to be used for prediction. 3D-Jury was also found to improve upon the competing servers' choice of the best structure model in most cases. The value of the 3D-Jury score as a generic reliability measure was also examined. We found that the 3D-Jury score separates bad models from good models better than the reliability score of the original server in 27 cases and falls short of it in only 5 cases out of a total of 38. We report the release of a new Meta Server feature: instant 3D-Jury scoring of uploaded user models. The 3D-Jury score continues to be a good indicator of structural model quality. It also provides a generic reliability score, especially important for models that were not assigned such by the original server. Individual structure modellers can also benefit from the 3D-Jury scoring system by testing their models in the new instant scoring feature http://meta.bioinfo.pl/compare_your_model_example.pl available in the Meta Server.

Evaluation of 3D-Jury on CASP7 models

PubMed Central

Kaján, László; Rychlewski, Leszek

2007-01-01

Background 3D-Jury, the structure prediction consensus method publicly available in the Meta Server , was evaluated using models gathered in the 7th round of the Critical Assessment of Techniques for Protein Structure Prediction (CASP7). 3D-Jury is an automated expert process that generates protein structure meta-predictions from sets of models obtained from partner servers. Results The performance of 3D-Jury was analysed for three aspects. First, we examined the correlation between the 3D-Jury score and a model quality measure: the number of correctly predicted residues. The 3D-Jury score was shown to correlate significantly with the number of correctly predicted residues, the correlation is good enough to be used for prediction. 3D-Jury was also found to improve upon the competing servers' choice of the best structure model in most cases. The value of the 3D-Jury score as a generic reliability measure was also examined. We found that the 3D-Jury score separates bad models from good models better than the reliability score of the original server in 27 cases and falls short of it in only 5 cases out of a total of 38. We report the release of a new Meta Server feature: instant 3D-Jury scoring of uploaded user models. Conclusion The 3D-Jury score continues to be a good indicator of structural model quality. It also provides a generic reliability score, especially important for models that were not assigned such by the original server. Individual structure modellers can also benefit from the 3D-Jury scoring system by testing their models in the new instant scoring feature available in the Meta Server. PMID:17711571

The Role of Genome Accessibility in Transcription Factor Binding in Bacteria.

PubMed

Gomes, Antonio L C; Wang, Harris H

2016-04-01

ChIP-seq enables genome-scale identification of regulatory regions that govern gene expression. However, the biological insights generated from ChIP-seq analysis have been limited to predictions of binding sites and cooperative interactions. Furthermore, ChIP-seq data often poorly correlate with in vitro measurements or predicted motifs, highlighting that binding affinity alone is insufficient to explain transcription factor (TF)-binding in vivo. One possibility is that binding sites are not equally accessible across the genome. A more comprehensive biophysical representation of TF-binding is required to improve our ability to understand, predict, and alter gene expression. Here, we show that genome accessibility is a key parameter that impacts TF-binding in bacteria. We developed a thermodynamic model that parameterizes ChIP-seq coverage in terms of genome accessibility and binding affinity. The role of genome accessibility is validated using a large-scale ChIP-seq dataset of the M. tuberculosis regulatory network. We find that accounting for genome accessibility led to a model that explains 63% of the ChIP-seq profile variance, while a model based in motif score alone explains only 35% of the variance. Moreover, our framework enables de novo ChIP-seq peak prediction and is useful for inferring TF-binding peaks in new experimental conditions by reducing the need for additional experiments. We observe that the genome is more accessible in intergenic regions, and that increased accessibility is positively correlated with gene expression and anti-correlated with distance to the origin of replication. Our biophysically motivated model provides a more comprehensive description of TF-binding in vivo from first principles towards a better representation of gene regulation in silico, with promising applications in systems biology.

Accuracy of SOFA score in prediction of 30-day outcome of critically ill patients.

PubMed

Safari, Saeed; Shojaee, Majid; Rahmati, Farhad; Barartloo, Alireza; Hahshemi, Behrooz; Forouzanfar, Mohammad Mehdi; Mohammadi, Elham

2016-12-01

Researchers have attempted to design various scoring systems to determine the severity and predict the outcome of critically ill patients. The present study aimed to evaluate the accuracy of SOFA score in predicting 1-month outcome of these patients in emergency department. The present study is a prospective cross-sectional study of >18 year old non-trauma critically ill patients presented to EDs of 3 hospitals, Tehran, Iran, during October 2014 to October 2015. Baseline characteristics, SOFA score variables, and 1-month outcome of patients were recorded and screening performance characteristics of the score were calculated using STATA 11 software. 140 patients with the mean age of 68.36 ± 18.62 years (18-95) were included (53.5% male). The most common complaints were decrease in level of consciousness (76.43%) and sepsis (60.0%), were the most frequent final diagnoses. Mean SOFA score of the patients was 7.13 ± 2.36 (minimum 2 and maximum 16). 72 (51.43%) patients died during the following 30 days and 16 (11.43%) patients were affected with multiple organ failure. Area under the ROC curve of SOFA score in predicting mortality of studied patients was 0.73 (95%CI: 0.65-0.81) (Fig. 2). Table 2 depicts screening performance characteristics of this scale in prediction of 1-month mortality in the best cut-off point of ≥7. At this cut-off point, sensitivity and specificity of SOFA in predicting 1-month mortality were 75% and 63.23%, respectively. Findings of the present study showed that SOFA scoring system has fair accuracy in predicting 1-month mortality of critically ill patients. However, until a more reliable scoring system is developed, SOFA might be useful for narrative prediction of patient outcome considering its acceptable likelihood ratios.

The AIMS65 Score Is a Useful Predictor of Mortality in Patients with Nonvariceal Upper Gastrointestinal Bleeding: Urgent Endoscopy in Patients with High AIMS65 Scores

PubMed Central

Park, Sun Wook; Song, Young Wook; Tak, Dae Hyun; Ahn, Byung Moo; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

2015-01-01

Background/Aims: To validate the AIMS65 score for predicting mortality of patients with nonvariceal upper gastrointestinal bleeding and to evaluate the effectiveness of urgent (<8 hours) endoscopic procedures in patients with high AIMS65 scores. Methods: This was a 5-year single-center, retrospective study. Nonvariceal, upper gastrointestinal bleeding was assessed by using the AIM65 and Rockall scores. Scores for mortality were assessed by calculating the area under the receiver-operating characteristic curve (AUROC). Patients with high AIMS65 scores (≥2) were allocated to either the urgent or non-urgent endoscopic procedure group. In-hospital mortality, success of endoscopic procedure, recurrence of bleeding, admission period, and dose of transfusion were compared between groups. Results: A total of 634 patients were analyzed. The AIMS65 score successfully predicted mortality (AUROC=0.943; 95% confidence interval [CI], 0.876 to 0.99) and was superior to the Rockall score (AUROC=0.856; 95% CI, 0.743 to 0.969) in predicting mortality. The group with high AIMS65 score included 200 patients. The urgent endoscopic procedure group had reduced hospitalization periods (p<0.05) Conclusions: AIMS65 score may be useful in predicting mortality in patients with nonvariceal upper gastrointestinal bleeding. Urgent endoscopic procedures in patients with high scores may be related to reduced hospitalization periods. PMID:26668799

Immediate Postoperative Pain Scores Predict Neck Pain Profile up to 1 Year Following Anterior Cervical Discectomy and Fusion.

PubMed

Adogwa, Owoicho; Elsamadicy, Aladine A; Vuong, Victoria D; Mehta, Ankit I; Vasquez, Raul A; Cheng, Joseph; Bagley, Carlos A; Karikari, Isaac O

2018-05-01

Retrospective cohort review. To assess whether immediate postoperative neck pain scores accurately predict 12-month visual analog scale-neck pain (VAS-NP) outcomes following Anterior Cervical Discectomy and Fusion surgery (ACDF). This was a retrospective study of 82 patients undergoing elective ACDF surgery at a major academic medical center. Patient reported outcomes measures VAS-NP scores were recorded on the first postoperative day, then at 6-weeks, 3, 6, and 12-months after surgery. Multivariate correlation and logistic regression methods were utilized to determine whether immediate postoperative VAS-NP score accurately predicted 1-year patient reported VAS-NP Scores. Overall, 46.3% male, 25.6% were smokers, and the mean age and body mass index (BMI) were 53.7 years and 28.28 kg/m 2 , respectively. There were significant correlations between immediate postoperative pain scores and neck pain scores at 6 weeks VAS-NP ( P = .0015), 6 months VAS-NP ( P = .0333), and 12 months VAS-NP ( P = .0247) after surgery. Furthermore, immediate postoperative pain score is an independent predictor of 6 weeks, 6 months, and 1 year VAS-NP scores. Our study suggests that immediate postoperative patient reported neck pain scores accurately predicts and correlates with 12-month VAS-NP scores after an ACDF procedure. Patients with high neck pain scores after surgery are more likely to report persistent neck pain 12 months after index surgery.

External Validation of the ASTRAL and DRAGON Scores for Prediction of Functional Outcome in Stroke.

PubMed

Cooray, Charith; Mazya, Michael; Bottai, Matteo; Dorado, Laura; Skoda, Ondrej; Toni, Danilo; Ford, Gary A; Wahlgren, Nils; Ahmed, Niaz

2016-06-01

ASTRAL (Acute Stroke Registry and Analysis of Lausanne) and DRAGON (includes dense middle cerebral artery sign, prestroke modified Rankin Scale score, age, glucose, onset to treatment, National Institutes of Health Stroke Scale score) are 2 recently developed scores for predicting functional outcome after acute stroke in unselected acute ischemic stroke patients and in patients treated with intravenous thrombolysis, respectively. We aimed to perform external validation of these scores to assess their predictive performance in the large multicentre Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. We calculated the ASTRAL and DRAGON scores in 36 131 and 33 716 patients, respectively, registered in Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register between 2003 and 2013. The proportion of patients with 3-month modified Rankin Scale scores of 3 to 6 was observed for each score point and compared with the predicted proportion according to the risk scores. Calibration was assessed using calibration plots, and predictive performance was assessed using area under the curve of the receiver operating characteristic. Multivariate logistic regression coefficients for the variables in the 2 scores were compared with the original derivation cohorts. The ASTRAL showed an area under the curve of 0.790 (95% confidence interval, 0.786-0.795) and the DRAGON an area under the curve of 0.774 (95% confidence interval, 0.769-0.779). All ASTRAL parameters except range of visual fields and all DRAGON parameters were significantly associated with functional outcome in multivariate analysis. The ASTRAL and DRAGON scores show an acceptable predictive performance. ASTRAL does not require imaging-data and therefore may have an advantage for the use in prehospital patient assessment. Prospective studies of both scores evaluating the impact of their use on patient outcomes after intravenous thrombolysis and endovascular therapy are needed. © 2016 American Heart Association, Inc.

Gender, TIMI risk score and in-hospital mortality in STEMI patients undergoing primary PCI: results from the Belgian STEMI registry.

PubMed

Gevaert, Sofie A; De Bacquer, Dirk; Evrard, Patrick; Convens, Carl; Dubois, Philippe; Boland, Jean; Renard, Marc; Beauloye, Christophe; Coussement, Patrick; De Raedt, Herbert; de Meester, Antoine; Vandecasteele, Els; Vranckx, Pascal; Sinnaeve, Peter R; Claeys, Marc J

2014-01-22

The relationship between the predictive performance of the TIMI risk score for STEMI and gender has not been evaluated in the setting of primary PCI (pPCI). Here, we compared in-hospital mortality and predictive performance of the TIMI risk score between Belgian women and men undergoing pPCI. In-hospital mortality was analysed in 8,073 (1,920 [23.8%] female and 6,153 [76.2%] male patients) consecutive pPCI-treated STEMI patients, included in the prospective, observational Belgian STEMI registry (January 2007 to February 2011). A multivariable logistic regression model, including TIMI risk score variables and gender, evaluated differences in in-hospital mortality between men and women. The predictive performance of the TIMI risk score according to gender was evaluated in terms of discrimination and calibration. Mortality rates for TIMI scores in women and men were compared. Female patients were older, had more comorbidities and longer ischaemic times. Crude in-hospital mortality was 10.1% in women vs. 4.9% in men (OR 2.2; 95% CI: 1.82-2.66, p<0.001). When adjusting for TIMI risk score variables, mortality remained higher in women (OR 1.47, 95% CI: 1.15-1.87, p=0.002). The TIMI risk score provided a good predictive discrimination and calibration in women as well as in men (c-statistic=0.84 [95% CI: 0.809-0.866], goodness-of-fit p=0.53 and c-statistic=0.89 [95% CI: 0.873-0.907], goodness-of-fit p=0.13, respectively), but mortality prediction for TIMI scores was better in men (p=0.02 for TIMI score x gender interaction). In the Belgian STEMI registry, pPCI-treated women had a higher in-hospital mortality rate even after correcting for TIMI risk score variables. The TIMI risk score was effective in predicting in-hospital mortality but performed slightly better in men. The database was registered with clinicaltrials.gov (NCT00727623).

Test anxiety and academic performance in chiropractic students.

PubMed

Zhang, Niu; Henderson, Charles N R

2014-01-01

Objective : We assessed the level of students' test anxiety, and the relationship between test anxiety and academic performance. Methods : We recruited 166 third-quarter students. The Test Anxiety Inventory (TAI) was administered to all participants. Total scores from written examinations and objective structured clinical examinations (OSCEs) were used as response variables. Results : Multiple regression analysis shows that there was a modest, but statistically significant negative correlation between TAI scores and written exam scores, but not OSCE scores. Worry and emotionality were the best predictive models for written exam scores. Mean total anxiety and emotionality scores for females were significantly higher than those for males, but not worry scores. Conclusion : Moderate-to-high test anxiety was observed in 85% of the chiropractic students examined. However, total test anxiety, as measured by the TAI score, was a very weak predictive model for written exam performance. Multiple regression analysis demonstrated that replacing total anxiety (TAI) with worry and emotionality (TAI subscales) produces a much more effective predictive model of written exam performance. Sex, age, highest current academic degree, and ethnicity contributed little additional predictive power in either regression model. Moreover, TAI scores were not found to be statistically significant predictors of physical exam skill performance, as measured by OSCEs.

Accuracy and Predictability of PANC-3 Scoring System over APACHE II in Acute Pancreatitis: A Prospective Study.

PubMed

Rathnakar, Surag Kajoor; Vishnu, Vikram Hubbanageri; Muniyappa, Shridhar; Prasath, Arun

2017-02-01

Acute Pancreatitis (AP) is one of the common conditions encountered in the emergency room. The course of the disease ranges from mild form to severe acute form. Most of these episodes are mild and spontaneously subsiding within 3 to 5 days. In contrast, Severe Acute Pancreatitis (SAP) occurring in around 15-20% of all cases, mortality can range between 10 to 85% across various centres and countries. In such a situation we need an indicator which can predict the outcome of an attack, as severe or mild, as early as possible and such an indicator should be sensitive and specific enough to trust upon. PANC-3 scoring is such a scoring system in predicting the outcome of an attack of AP. To assess the accuracy and predictability of PANC-3 scoring system over APACHE II in predicting severity in an attack of AP. This prospective study was conducted on 82 patients admitted with the diagnosis of pancreatitis. Investigations to evaluate PANC-3 and APACHE II were done on all the patients and the PANC-3 and APACHE II score was calculated. PANC-3 score has a sensitivity of 82.6% and specificity of 77.9%, the test had a Positive Predictive Value (PPV) of 0.59 and Negative Predictive Value (NPV) of 0.92. Sensitivity of APACHE II in predicting SAP was 91.3% and specificity was 96.6% with PPV of 0.91, NPV was 0.96. Our study shows that PANC-3 can be used to predict the severity of pancreatitis as efficiently as APACHE II. The interpretation of PANC-3 does not need expertise and can be applied at the time of admission which is an advantage when compared to classical scoring systems.

Do psychopathic traits assessed in mid-adolescence predict mental health, psychosocial, and antisocial, including criminal outcomes, over the subsequent 5 years?

PubMed

Hemphälä, Malin; Hodgins, Sheilagh

2014-01-01

To determine whether psychopathic traits assessed in mid-adolescence predicted mental health, psychosocial, and antisocial (including criminal) outcomes 5 years later and would thereby provide advantages over diagnosing conduct disorder (CD). Eighty-six women and 61 men were assessed in mid-adolescence when they first contacted a clinic for substance misuse and were reassessed 5 years later. Assessments in adolescence include the Psychopathy Checklist-Youth Version (PCL-YV), and depending on their age, either the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Aged Children or the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID). Assessments in early adulthood included the SCID, self-reports of psychosocial functioning, aggressive behaviour, and criminality and official criminal records. The antisocial facet score positively predicted the number of anxiety symptoms and likelihood of receiving treatment for substance use disorders (SUDs). Lifestyle and antisocial facet scores negatively predicted Global Assessment of Functioning scores. By contrast, the interpersonal score and male sex independently and positively predicted the number of months worked or studied, as did the interaction of Lifestyle × Sex indicating that among men, but not women, an increase in lifestyle facet score was associated with less time worked or studied. Interpersonal and antisocial scores positively predicted school drop-out. Antisocial facet scores predicted the number of symptoms of antisocial personality disorder, alcohol and SUDs, and violent and nonviolent criminality but much more strongly among males than females. Predictions from numbers of CD symptoms were similar. Psychopathic traits among adolescents who misuse substances predict an array of outcomes over the subsequent 5 years. Information on the levels of these traits may be useful for planning treatment.

Validation of a Clinical Scoring System for Outcome Prediction in Dogs with Acute Kidney Injury Managed by Hemodialysis.

PubMed

Segev, G; Langston, C; Takada, K; Kass, P H; Cowgill, L D

2016-05-01

A scoring system for outcome prediction in dogs with acute kidney injury (AKI) recently has been developed but has not been validated. The scoring system previously developed for outcome prediction will accurately predict outcome in a validation cohort of dogs with AKI managed with hemodialysis. One hundred fifteen client-owned dogs with AKI. Medical records of dogs with AKI treated by hemodialysis between 2011 and 2015 were reviewed. Dogs were included only if all variables required to calculate the final predictive score were available, and the 30-day outcome was known. A predictive score for 3 models was calculated for each dog. Logistic regression was used to evaluate the association of the final predictive score with each model's outcome. Receiver operating curve (ROC) analyses were performed to determine sensitivity and specificity for each model based on previously established cut-off values. Higher scores for each model were associated with decreased survival probability (P < .001). Based on previously established cut-off values, 3 models (models A, B, C) were associated with sensitivities/specificities of 73/75%, 71/80%, and 75/86%, respectively, and correctly classified 74-80% of the dogs. All models were simple to apply and allowed outcome prediction that closely corresponded with actual outcome in an independent cohort. As expected, accuracies were slightly lower compared with those from the previously reported cohort used initially to develop the models. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

ASTRAL, DRAGON and SEDAN scores predict stroke outcome more accurately than physicians.

PubMed

Ntaios, G; Gioulekas, F; Papavasileiou, V; Strbian, D; Michel, P

2016-11-01

ASTRAL, SEDAN and DRAGON scores are three well-validated scores for stroke outcome prediction. Whether these scores predict stroke outcome more accurately compared with physicians interested in stroke was investigated. Physicians interested in stroke were invited to an online anonymous survey to provide outcome estimates in randomly allocated structured scenarios of recent real-life stroke patients. Their estimates were compared to scores' predictions in the same scenarios. An estimate was considered accurate if it was within 95% confidence intervals of actual outcome. In all, 244 participants from 32 different countries responded assessing 720 real scenarios and 2636 outcomes. The majority of physicians' estimates were inaccurate (1422/2636, 53.9%). 400 (56.8%) of physicians' estimates about the percentage probability of 3-month modified Rankin score (mRS) > 2 were accurate compared with 609 (86.5%) of ASTRAL score estimates (P < 0.0001). 394 (61.2%) of physicians' estimates about the percentage probability of post-thrombolysis symptomatic intracranial haemorrhage were accurate compared with 583 (90.5%) of SEDAN score estimates (P < 0.0001). 160 (24.8%) of physicians' estimates about post-thrombolysis 3-month percentage probability of mRS 0-2 were accurate compared with 240 (37.3%) DRAGON score estimates (P < 0.0001). 260 (40.4%) of physicians' estimates about the percentage probability of post-thrombolysis mRS 5-6 were accurate compared with 518 (80.4%) DRAGON score estimates (P < 0.0001). ASTRAL, DRAGON and SEDAN scores predict outcome of acute ischaemic stroke patients with higher accuracy compared to physicians interested in stroke. © 2016 EAN.

Do MCAT scores predict USMLE scores? An analysis on 5 years of medical student data.

PubMed

Gauer, Jacqueline L; Wolff, Josephine M; Jackson, J Brooks

2016-01-01

The purpose of this study was to determine the associations and predictive values of Medical College Admission Test (MCAT) component and composite scores prior to 2015 with U.S. Medical Licensure Exam (USMLE) Step 1 and Step 2 Clinical Knowledge (CK) scores, with a focus on whether students scoring low on the MCAT were particularly likely to continue to score low on the USMLE exams. Multiple linear regression, correlation, and chi-square analyses were performed to determine the relationship between MCAT component and composite scores and USMLE Step 1 and Step 2 CK scores from five graduating classes (2011-2015) at the University of Minnesota Medical School ( N =1,065). The multiple linear regression analyses were both significant ( p <0.001). The three MCAT component scores together explained 17.7% of the variance in Step 1 scores ( p< 0.001) and 12.0% of the variance in Step 2 CK scores ( p <0.001). In the chi-square analyses, significant, albeit weak associations were observed between almost all MCAT component scores and USMLE scores (Cramer's V ranged from 0.05 to 0.24). Each of the MCAT component scores was significantly associated with USMLE Step 1 and Step 2 CK scores, although the effect size was small. Being in the top or bottom scoring range of the MCAT exam was predictive of being in the top or bottom scoring range of the USMLE exams, although the strengths of the associations were weak to moderate. These results indicate that MCAT scores are predictive of student performance on the USMLE exams, but, given the small effect sizes, should be considered as part of the holistic view of the student.

Do MCAT scores predict USMLE scores? An analysis on 5 years of medical student data

PubMed Central

Gauer, Jacqueline L.; Wolff, Josephine M.; Jackson, J. Brooks

2016-01-01

Introduction The purpose of this study was to determine the associations and predictive values of Medical College Admission Test (MCAT) component and composite scores prior to 2015 with U.S. Medical Licensure Exam (USMLE) Step 1 and Step 2 Clinical Knowledge (CK) scores, with a focus on whether students scoring low on the MCAT were particularly likely to continue to score low on the USMLE exams. Method Multiple linear regression, correlation, and chi-square analyses were performed to determine the relationship between MCAT component and composite scores and USMLE Step 1 and Step 2 CK scores from five graduating classes (2011–2015) at the University of Minnesota Medical School (N=1,065). Results The multiple linear regression analyses were both significant (p<0.001). The three MCAT component scores together explained 17.7% of the variance in Step 1 scores (p<0.001) and 12.0% of the variance in Step 2 CK scores (p<0.001). In the chi-square analyses, significant, albeit weak associations were observed between almost all MCAT component scores and USMLE scores (Cramer's V ranged from 0.05 to 0.24). Discussion Each of the MCAT component scores was significantly associated with USMLE Step 1 and Step 2 CK scores, although the effect size was small. Being in the top or bottom scoring range of the MCAT exam was predictive of being in the top or bottom scoring range of the USMLE exams, although the strengths of the associations were weak to moderate. These results indicate that MCAT scores are predictive of student performance on the USMLE exams, but, given the small effect sizes, should be considered as part of the holistic view of the student. PMID:27702431

Can Mapping Algorithms Based on Raw Scores Overestimate QALYs Gained by Treatment? A Comparison of Mappings Between the Roland-Morris Disability Questionnaire and the EQ-5D-3L Based on Raw and Differenced Score Data.

PubMed

Madan, Jason; Khan, Kamran A; Petrou, Stavros; Lamb, Sarah E

2017-05-01

Mapping algorithms are increasingly being used to predict health-utility values based on responses or scores from non-preference-based measures, thereby informing economic evaluations. We explored whether predictions in the EuroQol 5-dimension 3-level instrument (EQ-5D-3L) health-utility gains from mapping algorithms might differ if estimated using differenced versus raw scores, using the Roland-Morris Disability Questionnaire (RMQ), a widely used health status measure for low back pain, as an example. We estimated algorithms mapping within-person changes in RMQ scores to changes in EQ-5D-3L health utilities using data from two clinical trials with repeated observations. We also used logistic regression models to estimate response mapping algorithms from these data to predict within-person changes in responses to each EQ-5D-3L dimension from changes in RMQ scores. Predicted health-utility gains from these mappings were compared with predictions based on raw RMQ data. Using differenced scores reduced the predicted health-utility gain from a unit decrease in RMQ score from 0.037 (standard error [SE] 0.001) to 0.020 (SE 0.002). Analysis of response mapping data suggests that the use of differenced data reduces the predicted impact of reducing RMQ scores across EQ-5D-3L dimensions and that patients can experience health-utility gains on the EQ-5D-3L 'usual activity' dimension independent from improvements captured by the RMQ. Mappings based on raw RMQ data overestimate the EQ-5D-3L health utility gains from interventions that reduce RMQ scores. Where possible, mapping algorithms should reflect within-person changes in health outcome and be estimated from datasets containing repeated observations if they are to be used to estimate incremental health-utility gains.

Prognostic Value of the Thrombolysis in Myocardial Infarction Risk Score in ST-Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction (from the EPHESUS Trial).

PubMed

Popovic, Batric; Girerd, Nicolas; Rossignol, Patrick; Agrinier, Nelly; Camenzind, Edoardo; Fay, Renaud; Pitt, Bertram; Zannad, Faiez

2016-11-15

The Thrombolysis in Myocardial Infarction (TIMI) risk score remains a robust prediction tool for short-term and midterm outcome in the patients with ST-elevation myocardial infarction (STEMI). However, the validity of this risk score in patients with STEMI with reduced left ventricular ejection fraction (LVEF) remains unclear. A total of 2,854 patients with STEMI with early coronary revascularization participating in the randomized EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial were analyzed. TIMI risk score was calculated at baseline, and its predictive value was evaluated using C-indexes from Cox models. The increase in reclassification of other variables in addition to TIMI score was assessed using the net reclassification index. TIMI risk score had a poor predictive accuracy for all-cause mortality (C-index values at 30 days and 1 year ≤0.67) and recurrent myocardial infarction (MI; C-index values ≤0.60). Among TIMI score items, diabetes/hypertension/angina, heart rate >100 beats/min, and systolic blood pressure <100 mm Hg were inconsistently associated with survival, whereas none of the TIMI score items, aside from age, were significantly associated with MI recurrence. Using a constructed predictive model, lower LVEF, lower estimated glomerular filtration rate (eGFR), and previous MI were significantly associated with all-cause mortality. The predictive accuracy of this model, which included LVEF and eGFR, was fair for both 30-day and 1-year all-cause mortality (C-index values ranging from 0.71 to 0.75). In conclusion, TIMI risk score demonstrates poor discrimination in predicting mortality or recurrent MI in patients with STEMI with reduced LVEF. LVEF and eGFR are major factors that should not be ignored by predictive risk scores in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS.

PubMed

Beduschi, Murilo Gamba; Mello, André Luiz Parizi; VON-Mühlen, Bruno; Franzon, Orli

2016-03-01

About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis.

THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS

PubMed Central

BEDUSCHI, Murilo Gamba; MELLO, André Luiz Parizi; VON-MÜHLEN, Bruno; FRANZON, Orli

2016-01-01

Background : About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. Objective : To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Methods : Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Results : Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. Conclusion : The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis. PMID:27120730

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma.

PubMed

Tiveron, Rogério Costa; de Freitas, Luiz Carlos Conti; Figueiredo, David L; Serafini, Luciano N; Mamede, Rui Celso Martins; Zago, Marco A

2012-01-01

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer. This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx. Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared. The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%). S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.

Prognostic capability of different liver disease scoring systems for prediction of early mortality after transjugular intrahepatic portosystemic shunt creation.

PubMed

Gaba, Ron C; Couture, Patrick M; Bui, James T; Knuttinen, M Grace; Walzer, Natasha M; Kallwitz, Eric R; Berkes, Jamie L; Cotler, Scott J

2013-03-01

To compare the performance of various liver disease scoring systems in predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, eight scoring systems were used to grade liver disease in 211 patients (male-to-female ratio = 131:80; mean age, 54 y) before TIPS creation from 1999-2011. Scoring systems included bilirubin level, Child-Pugh (CP) score, Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease sodium (MELD-Na) score, Emory score, prognostic index (PI), Acute Physiology and Chronic Health Evaluation (APACHE) 2 score, and Bonn TIPS early mortality (BOTEM) score. Medical record review was used to identify 30-day and 90-day clinical outcomes. The relationship of scoring parameters with mortality outcomes was assessed with multivariate analysis, and the relative ability of systems to predict mortality after TIPS creation was evaluated by comparing area under receiver operating characteristic (AUROC) curves. TIPS were successfully created for variceal hemorrhage (n = 121), ascites (n = 72), hepatic hydrothorax (n = 15), and portal vein thrombosis (n = 3). All scoring systems had a significant association with 30-day and 90-day mortality (P<.050 in each case) on multivariate analysis. Based on 30-day and 90-day AUROC, MELD (0.878, 0.816) and MELD-Na (0.863, 0.823) scores had the best capability to predict early mortality compared with bilirubin (0.786, 0.749), CP (0.822, 0.771), Emory (0.786, 0.681), PI (0.854, 0.760), APACHE 2 (0.836, 0.735), and BOTEM (0.798, 0.698), with statistical superiority over bilirubin, Emory, and BOTEM scores. Several liver disease scoring systems have prognostic value for early mortality after TIPS creation. MELD and MELD-Na scores most effectively predict survival after TIPS creation. Copyright © 2013. Published by Elsevier Inc.

The New York risk score for in-hospital and 30-day mortality for coronary artery bypass graft surgery.

PubMed

Hannan, Edward L; Farrell, Louise Szypulski; Wechsler, Andrew; Jordan, Desmond; Lahey, Stephen J; Culliford, Alfred T; Gold, Jeffrey P; Higgins, Robert S D; Smith, Craig R

2013-01-01

Simplified risk scores for coronary artery bypass graft surgery are frequently in lieu of more complicated statistical models and are valuable for informed consent and choice of intervention. Previous risk scores have been based on in-hospital mortality, but a substantial number of patients die within 30 days of the procedure. These deaths should also be accounted for, so we have developed a risk score based on in-hospital and 30-day mortality. New York's Cardiac Surgery Reporting System was used to develop an in-hospital and 30-day logistic regression model for patients undergoing coronary artery bypass graft surgery in 2009, and this model was converted into a simple linear risk score that provides estimated in-hospital and 30-day mortality rates for different values of the score. The accuracy of the risk score in predicting mortality was tested. This score was also validated by applying it to 2008 New York coronary artery bypass graft data. Subsequent analyses evaluated the ability of the risk score to predict complications and length of stay. The overall in-hospital and 30-day mortality rate for the 10,148 patients in the study was 1.79%. There are seven risk factors comprising the score, with risk factor scores ranging from 1 to 5, and the highest possible total score is 23. The score accurately predicted mortality in 2009 as well as in 2008, and was strongly correlated with complications and length of stay. The risk score is a simple way of estimating short-term mortality that accurately predicts mortality in the year the model was developed as well as in the previous year. Perioperative complications and length of stay are also well predicted by the risk score. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of the Occlusion Duration on the Performance of J-CTO Score in Predicting Failure of Percutaneous Coronary Intervention for Chronic Total Occlusion.

PubMed

de Castro-Filho, Antonio; Lamas, Edgar Stroppa; Meneguz-Moreno, Rafael A; Staico, Rodolfo; Siqueira, Dimytri; Costa, Ricardo A; Braga, Sergio N; Costa, J Ribamar; Chamié, Daniel; Abizaid, Alexandre

2017-06-01

The present study examined the association between Multicenter CTO Registry in Japan (J-CTO) score in predicting failure of percutaneous coronary intervention (PCI) correlating with the estimated duration of chronic total occlusion (CTO). The J-CTO score does not incorporate estimated duration of the occlusion. This was an observational retrospective study that involved all consecutive procedures performed at a single tertiary-care cardiology center between January 2009 and December 2014. A total of 174 patients, median age 59.5 years (interquartile range [IQR], 53-65 years), undergoing CTO-PCI were included. The median estimated occlusion duration was 7.5 months (IQR, 4.0-12.0 months). The lesions were classified as easy (score = 0), intermediate (score = 1), difficult (score = 2), and very difficult (score ≥3) in 51.1%, 33.9%, 9.2%, and 5.7% of the patients, respectively. Failure rate significantly increased with higher J-CTO score (7.9%, 20.3%, 50.0%, and 70.0% in groups with J-CTO scores of 0, 1, 2, and ≥3, respectively; P<.001). There was no significant difference in success rate according to estimated duration of occlusion (P=.63). Indeed, J-CTO score predicted failure of CTO-PCI independently of the estimated occlusion duration (P=.24). Areas under receiver-operating characteristic curves were computed and it was observed that for each occlusion time period, the discriminatory capacity of the J-CTO score in predicting CTO-PCI failure was good, with a C-statistic >0.70. The estimated duration of occlusion had no influence on the J-CTO score performance in predicting failure of PCI in CTO lesions. The probability of failure was mainly determined by grade of lesion complexity.

Cost calculation and prediction in adult intensive care: a ground-up utilization study.

PubMed

Moran, J L; Peisach, A R; Solomon, P J; Martin, J

2004-12-01

The ability of various proxy cost measures, including therapeutic activity scores (TISS and Omega) and cumulative daily severity of illness scores, to predict individual ICU patient costs was assessed in a prospective "ground-up" utilization costing study over a six month period in 1991. Daily activity (TISS and Omega scores) and utilization in consecutive admissions to three adult university associated ICUs was recorded by dedicated data collectors. Cost prediction used linear regression with determination (80%) and validation (20%) data sets. The cohort, 1333 patients, had a mean (SD) age 57.5 (19.4) years, (41% female) and admission APACHE III score of 58 (27). ICU length of stay and mortality were 3.9 (6.1) days and 17.6% respectively. Mean total TISS and Omega scores were 117 (157) and 72 (113) respectively. Mean patient costs per ICU episode (1991 dollar AUS) were dollar 6801 (dollar 10311), with median costs of dollar 2534, range dollar 106 to dollar 95,602. Dominant cost fractions were nursing 43.3% and overheads 16.9%. Inflation adjusted year 2002 (mean) costs were dollar 9343 (dollar AUS). Total costs in survivors were predicted by Omega score, summed APACHE III score and ICU length of stay; determination R2, 0.91; validation 0.88. Omega was the preferred activity score. Without the Omega score, predictors were age, summed APACHE III score and ICU length of stay; determination R2, 0.73; validation 0.73. In non-survivors, predictors were age and ICU length of stay (plus interaction), and Omega score (determination R2, 0.97; validation 0.91). Patient costs may be predicted by a combination of ICU activity indices and severity scores.

The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in atrial fibrillation: the MAQI(2) experience.

PubMed

Barnes, Geoffrey D; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Froehlich, James B; Kaatz, Scott

2014-08-01

Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. 2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. 110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0±0.8years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. The CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Performance and Admission Variables as Predictors of Passage of the National Physical Therapy Examination.

PubMed

Meiners, Kelly M; Rush, Douglas K

2017-01-01

Prior studies have explored variables that had predictive relationships with National Physical Therapy Examination (NPTE) score or NPTE failure. The purpose of this study was to explore whether certain variables were predictive of test-takers' first-time score on the NPTE. The population consisted of 134 students who graduated from the university's Professional DPT Program in 2012 to 2014. This quantitative study used a retrospective design. Two separate data analyses were conducted. First, hierarchical linear multiple regression (HMR) analysis was performed to determine which variables were predictive of first-time NPTE score. Second, a correlation analysis was performed on all 18 Physical Therapy Clinical Performance Instrument (PT CPI) 2006 category scores obtained during the first long-term clinical rotation, overall PT CPI 2006 score, and NPTE passage. With all variables entered, the HMR model predicted 39% of the variance seen in NPTE scores. The HMR results showed that physical therapy program first-year GPA (1PTGPA) was the strongest predictor and explained 24% of the variance in NPTE scores (b=0.572, p<0.001). The correlational analysis found no statistically significant correlation between the 18 PT CPI 2006 category scores, overall PT CPI 2006 score, and NPTE passage. As 1PTGPA had the most significant contribution to prediction of NPTE scores, programs need to monitor first-year students who display academic difficulty. PT CPI version 2006 scores were significantly correlated with each other, but not with NPTE score or NPTE passage. Both tools measure many of the same professional requirements but use different modes of assessment, and they may be considered complementary tools to gain a full picture of both the student's ability and skills.

Small Size at Birth or Abnormal Intrauterine Growth Trajectory: Which Matters More for Child Growth?

PubMed Central

Hutcheon, Jennifer A.; Jacobsen, Geir W.; Kramer, Michael S.; Martinussen, Marit; Platt, Robert W.

2016-01-01

Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986–1988). Size at birth was classified using birth weight-for-gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks’ gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (β = 0.24 (95% confidence interval (CI): 0.18, 0.31), β = 0.16 (95% CI: 0.09, 0.23), β = 0.08 (95% CI: 0.01, 0.16), and β = 0.37 (95% CI: 0.22, 0.52), respectively). However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R2 increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional insight into child growth beyond that obtained from absolute size at birth. PMID:27257112

National Institutes of Health Stroke Scale-Time Score Predicts Outcome after Endovascular Therapy in Acute Ischemic Stroke: A Retrospective Single-Center Study.

PubMed

Todo, Kenichi; Sakai, Nobuyuki; Kono, Tomoyuki; Hoshi, Taku; Imamura, Hirotoshi; Adachi, Hidemitsu; Kohara, Nobuo

2016-05-01

Outcomes after successful endovascular therapy in acute ischemic stroke are associated with onset-to-reperfusion time (ORT) and the National Institutes of Health Stroke Scale (NIHSS) score. In intravenous recombinant tissue plasminogen activator therapy, the NIHSS-time score, calculated by multiplying onset-to-treatment time with the NIHSS score, has been shown to predict clinical outcomes. In this study, we assessed whether a similar combination of the ORT and the NIHSS score can be applied to predict the outcomes after endovascular therapy. We retrospectively reviewed the charts of 128 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy. We analyzed the association of the ORT, the NIHSS score, and the NIHSS-time score with good outcome (modified Rankin Scale score ≤ 2 at 3 months). Good outcome rates for patients with NIHSS-time scores of 84.7 or lower, scores higher than 84.7 up to 127.5 or lower, and scores higher than 127.5 were 72.1%, 44.2%, and 14.3%, respectively (P < .01). Multivariate logistic regression analysis revealed that the NIHSS-time score was an independent predictor of good outcomes (odds ratio, .372; 95% confidence interval, .175-.789) after adjusting for age, sex, internal carotid artery occlusion, plasma glucose level, ORT, and NIHSS score. The NIHSS-time score can predict good clinical outcomes after endovascular treatment. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A Comparative Study of Glasgow Coma Scale and Full Outline of Unresponsiveness Scores for Predicting Long-Term Outcome After Brain Injury.

PubMed

McNett, Molly M; Amato, Shelly; Philippbar, Sue Ann

2016-01-01

The aim of this study was to compare predictive ability of hospital Glasgow Coma Scale (GCS) scores and scores obtained using a novel coma scoring tool (the Full Outline of Unresponsiveness [FOUR] scale) on long-term outcomes among patients with traumatic brain injury. Preliminary research of the FOUR scale suggests that it is comparable with GCS for predicting mortality and functional outcome at hospital discharge. No research has investigated relationships between coma scores and outcome 12 months postinjury. This is a prospective cohort study. Data were gathered on adult patients with traumatic brain injury admitted to urban level I trauma center. GCS and FOUR scores were assigned at 24 and 72 hours and at hospital discharge. Glasgow Outcome Scale scores were assigned at 6 and 12 months. The sample size was n = 107. Mean age was 53.5 (SD = ±21, range = 18-91) years. Spearman correlations were comparable and strongest among discharge GCS and FOUR scores and 12-month outcome (r = .73, p < .000; r = .72, p < .000). Multivariate regression models indicate that age and discharge GCS were the strongest predictors of outcome. Areas under the curve were similar for GCS and FOUR scores, with discharge scores occupying the largest areas. GCS and FOUR scores were comparable in bivariate associations with long-term outcome. Discharge coma scores performed best for both tools, with GCS discharge scores predictive in multivariate models.

Birth timing and behavioral responsiveness predict individual differences in the mother-infant relationship and infant behavior during weaning and maternal breeding

PubMed Central

Vandeleest, Jessica J.; Capitanio, John P.

2012-01-01

There is a great deal of variability in mother-infant interactions and infant behavior across the first year of life in rhesus monkeys. The current paper has two specific aims: 1) to determine if birth timing predicts variability in the mother-infant relationship and infant behavior during weaning and maternal breeding, and 2) to identify predictors of infant behavior during a period of acute challenge, maternal breeding. Forty-one mother-infant pairs were observed during weaning when infants were 4.5 months old, and 33 were followed through maternal breeding. Subjective ratings of 16 adjectives reflecting qualities of maternal attitude, mother-infant interactions, and infant attitude were factor analyzed to construct factors relating to the mother-infant relationship (Relaxed and Aggressive), and infant behavior (Positive Engagement and Distress). During weaning, late born infants were more Positively Engaged than peak born infants (ANOVA, P < 0.05); however, birth timing did not affect the mother-infant relationship factors Relaxed and Aggressive or the infant attitude factor Distress. During maternal breeding early born infants had less Relaxed relationships with their mothers than peak or late born infants, higher Positive Engagement scores than peak or late born infants, and tended to have higher Distress scores than peak born infants (Repeated-measures ANOVA, P < 0.05). In addition, Distress scores were higher during maternal breeding than during the pre- and post-breeding phases. Finally, multiple regression (P < 0.05) indicated that while infant behavioral responsiveness predicted infant Positive Engagement during the acute challenge of maternal breeding, qualities of the mother-infant relationship predicted infant Distress. These data suggest that birth timing influences the patterns of mother-infant interactions during weaning and maternal breeding. Additionally, infant behavioral responsiveness and mother-infant relationship quality impact infant social engagement and affect expression, respectively. PMID:24436198

Investigating the Written Exam Scores' Prediction Power of TEOG Exam Scores

ERIC Educational Resources Information Center

Kontas, Hakki; Özpolat, Esen Turan

2017-01-01

The purpose of this study was to investigate exam scores' predicting Transition from Primary to Secondary Education (TEOG) exam scores. The research data were obtained from the records of 1035 students studying at the first term of eighth grade in 2015-2016 academic year in e-school system. The research was on relational screening model. Linear…

The peripheral messenger RNA expression of glycogen synthase kinase-3β genes in Alzheimer's disease patients: a preliminary study.

PubMed

Sheng, Jian-Hua; Ng, Tze-Pin; Li, Chun-Bo; Lu, Guang-Hua; He, Wei; Qian, Yi-Ping; Wang, Jing-Hua; Yu, Shun-Ying

2012-12-01

To explore the peripheral leucocytic messenger RNA (mRNA) expression of glycogen synthase kinase-3β (GSK-3β) gene in Alzheimer's disease (AD) patients. Using TaqMan relative quantitative real-time polymerase chain reaction, we analyzed leucocytic gene expression of GSK-3β in 48 AD patients and 49 healthy controls. Clinical data of AD patients were also collected. The mRNA expression level of the GSK-3β gene was significantly higher in the AD group (3.13±0.62) than in the normal group (2.77±0.77). Correlational analyses showed that the mRNA expression level of GSK-3β gene in AD patients was associated with the age of onset (P=0.047), age (P=0.055), and Behavioral Pathology in Alzheimer's Disease Rating Scale total score (P=0.062) and subscores: aggressiveness score (P=0.073) and anxieties and phobias score (P=0.067). Through multivariate regression model, older age, higher anxieties and phobias score and aggressiveness score were associated with higher mRNA expression level of GSK-3β gene. In AD patients, the mRNA expression level of the GSK-3β gene is increased and may be related to age and behavioural pathology in AD. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.

Quantitative prediction of drug side effects based on drug-related features.

PubMed

Niu, Yanqing; Zhang, Wen

2017-09-01

Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.

Validation of a prediction model that allows direct comparison of the Oxford Knee Score and American Knee Society clinical rating system.

PubMed

Maempel, J F; Clement, N D; Brenkel, I J; Walmsley, P J

2015-04-01

This study demonstrates a significant correlation between the American Knee Society (AKS) Clinical Rating System and the Oxford Knee Score (OKS) and provides a validated prediction tool to estimate score conversion. A total of 1022 patients were prospectively clinically assessed five years after TKR and completed AKS assessments and an OKS questionnaire. Multivariate regression analysis demonstrated significant correlations between OKS and the AKS knee and function scores but a stronger correlation (r = 0.68, p < 0.001) when using the sum of the AKS knee and function scores. Addition of body mass index and age (other statistically significant predictors of OKS) to the algorithm did not significantly increase the predictive value. The simple regression model was used to predict the OKS in a group of 236 patients who were clinically assessed nine to ten years after TKR using the AKS system. The predicted OKS was compared with actual OKS in the second group. Intra-class correlation demonstrated excellent reliability (r = 0.81, 95% confidence intervals 0.75 to 0.85) for the combined knee and function score when used to predict OKS. Our findings will facilitate comparison of outcome data from studies and registries using either the OKS or the AKS scores and may also be of value for those undertaking meta-analyses and systematic reviews. ©2015 The British Editorial Society of Bone & Joint Surgery.

Predictive power of the grace score in population with diabetes.

PubMed

Baeza-Román, Anna; de Miguel-Balsa, Eva; Latour-Pérez, Jaime; Carrillo-López, Andrés

2017-12-01

Current clinical practice guidelines recommend risk stratification in patients with acute coronary syndrome (ACS) upon admission to hospital. Diabetes mellitus (DM) is widely recognized as an independent predictor of mortality in these patients, although it is not included in the GRACE risk score. The objective of this study is to validate the GRACE risk score in a contemporary population and particularly in the subgroup of patients with diabetes, and to test the effects of including the DM variable in the model. Retrospective cohort study in patients included in the ARIAM-SEMICYUC registry, with a diagnosis of ACS and with available in-hospital mortality data. We tested the predictive power of the GRACE score, calculating the area under the ROC curve. We assessed the calibration of the score and the predictive ability based on type of ACS and the presence of DM. Finally, we evaluated the effect of including the DM variable in the model by calculating the net reclassification improvement. The GRACE score shows good predictive power for hospital mortality in the study population, with a moderate degree of calibration and no significant differences based on ACS type or the presence of DM. Including DM as a variable did not add any predictive value to the GRACE model. The GRACE score has an appropriate predictive power, with good calibration and clinical applicability in the subgroup of diabetic patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

A Predictive Model of the Oxygen and Heme Regulatory Network in Yeast

PubMed Central

Kundaje, Anshul; Xin, Xiantong; Lan, Changgui; Lianoglou, Steve; Zhou, Mei; Zhang, Li; Leslie, Christina

2008-01-01

Deciphering gene regulatory mechanisms through the analysis of high-throughput expression data is a challenging computational problem. Previous computational studies have used large expression datasets in order to resolve fine patterns of coexpression, producing clusters or modules of potentially coregulated genes. These methods typically examine promoter sequence information, such as DNA motifs or transcription factor occupancy data, in a separate step after clustering. We needed an alternative and more integrative approach to study the oxygen regulatory network in Saccharomyces cerevisiae using a small dataset of perturbation experiments. Mechanisms of oxygen sensing and regulation underlie many physiological and pathological processes, and only a handful of oxygen regulators have been identified in previous studies. We used a new machine learning algorithm called MEDUSA to uncover detailed information about the oxygen regulatory network using genome-wide expression changes in response to perturbations in the levels of oxygen, heme, Hap1, and Co2+. MEDUSA integrates mRNA expression, promoter sequence, and ChIP-chip occupancy data to learn a model that accurately predicts the differential expression of target genes in held-out data. We used a novel margin-based score to extract significant condition-specific regulators and assemble a global map of the oxygen sensing and regulatory network. This network includes both known oxygen and heme regulators, such as Hap1, Mga2, Hap4, and Upc2, as well as many new candidate regulators. MEDUSA also identified many DNA motifs that are consistent with previous experimentally identified transcription factor binding sites. Because MEDUSA's regulatory program associates regulators to target genes through their promoter sequences, we directly tested the predicted regulators for OLE1, a gene specifically induced under hypoxia, by experimental analysis of the activity of its promoter. In each case, deletion of the candidate regulator resulted in the predicted effect on promoter activity, confirming that several novel regulators identified by MEDUSA are indeed involved in oxygen regulation. MEDUSA can reveal important information from a small dataset and generate testable hypotheses for further experimental analysis. Supplemental data are included. PMID:19008939

CBM Reading, Mathematics, and Written Expression at the Secondary Level: Examining Latent Composite Relations Among Indices and Unique Predictions With a State Achievement Test

PubMed Central

Codding, Robin S.; Petscher, Yaacov; Truckenmiller, Adrea

2015-01-01

A paucity of research has examined the utility of curriculum-based measurement (CBM) for data-based decision making at the secondary level. As schools move to multitiered systems of service delivery, it is conceivable that multiple screening measures will be used that address various academic subject areas. The value of including different CBM indices measures is not well understood. The purpose of this study was to (a) examine the relationship among a variety of reading, writing, and mathematics CBM indices administered to 249 seventh-grade students; (b) investigate amount and patterns of growth; and (c) examine predictive validity to a high-stakes state test using latent factor analysis and multiple indicator growth models. Results indicated strong correspondence among CBM types for fall static scores but weak relationships among slopes. Different patterns of growth were yielded for CBM writing than for CBM reading and mathematics. Findings from this study suggested that although reading, mathematics, and writing CBM were independently and moderately related to both English Language Arts and Math test scores, reading was the strongest predictor when all 3 CBM constructs were considered jointly. PMID:26347201

CBM Reading, Mathematics, and Written Expression at the Secondary Level: Examining Latent Composite Relations Among Indices and Unique Predictions With a State Achievement Test.

PubMed

Codding, Robin S; Petscher, Yaacov; Truckenmiller, Adrea

2015-05-01

A paucity of research has examined the utility of curriculum-based measurement (CBM) for data-based decision making at the secondary level. As schools move to multitiered systems of service delivery, it is conceivable that multiple screening measures will be used that address various academic subject areas. The value of including different CBM indices measures is not well understood. The purpose of this study was to (a) examine the relationship among a variety of reading, writing, and mathematics CBM indices administered to 249 seventh-grade students; (b) investigate amount and patterns of growth; and (c) examine predictive validity to a high-stakes state test using latent factor analysis and multiple indicator growth models. Results indicated strong correspondence among CBM types for fall static scores but weak relationships among slopes. Different patterns of growth were yielded for CBM writing than for CBM reading and mathematics. Findings from this study suggested that although reading, mathematics, and writing CBM were independently and moderately related to both English Language Arts and Math test scores, reading was the strongest predictor when all 3 CBM constructs were considered jointly.

Relations among Teachers’ Emotion Socialization Beliefs and Practices, and Preschoolers’ Emotional Competence

PubMed Central

Morris, Carol A.S.; Denham, Susanne A.; Bassett, Hideko H.; Curby, Timothy W.

2013-01-01

Research Findings Utilizing a three-part model of emotion socialization that includes Modeling, Contingent Responding, and Teaching, this study examined the associations between 44 teachers’ self-reported and observed emotion socialization practices and 326 preschoolers’ emotion knowledge and observed emotional behavior. Multi-level analyses revealed that the majority of the variance in the children’s emotion knowledge scores and observed emotional behavior was predicted by factors within, rather than between, classrooms. Teachers’ use of all three emotion socialization techniques did contribute to the prediction of the children’s scores; however, the nature of these associations differed by children’s age and gender. Practice or Policy The development of children’s emotional competence is a complex, multi-faceted process in which many interaction partners play a role; early childhood teachers act as emotion socialization agents for the children in their care by modeling emotions, responding either supportively or punitively to children’s expressions of emotions, and engaging in direct instruction regarding emotional experience. This research may provide a basis for potential future interventions designed to assist teachers in developing their own emotion socialization skills so that they can be more effective emotion socialization agents for the children in their care. PMID:24159256

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

PubMed

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando; Treviño, Victor

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer

PubMed Central

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures. PMID:29596496

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Does the NBME Surgery Shelf exam constitute a "double jeopardy" of USMLE Step 1 performance?

PubMed

Ryan, Michael S; Colbert-Getz, Jorie M; Glenn, Salem N; Browning, Joel D; Anand, Rahul J

2017-02-01

Scores from the NBME Subject Examination in Surgery (Surgery Shelf) positively correlate with United States Medical Licensing Examination Step 1 (Step 1). Based on this relationship, the authors evaluated the predictive value of Step 1 on the Surgery Shelf. Surgery Shelf standard scores were substituted for Step 1 standard scores for 395 students in 2012-2014 at one medical school. Linear regression was used to determine how well Step 1 scores predicted Surgery Shelf scores. Percent match between original (with Shelf) and modified (with Step 1) clerkship grades were computed. Step 1 scores significantly predicted Surgery Shelf scores, R 2  = 0.42, P < 0.001. For every point increase in Step 1, a Surgery Shelf score increased by 0.30 points. Seventy-seven percent of original grades matched the modified grades. Replacing Surgery Shelf scores with Step 1 scores did not have an effect on the majority of final clerkship grades. This observation raises concern over use of Surgery Shelf scores as a measure of knowledge obtained during the Surgery clerkship. Copyright © 2016 Elsevier Inc. All rights reserved.

Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

PubMed

Tana, Claudio; Tana, Marco; Rossi, Stefano; Silingardi, Mauro; Schiavone, Cosima

2016-09-01

Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p < 0.0001). A significant difference was also found between the groups of NAFLD severity (p < 0.0001). There was also a difference between HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls (p < 0.0001) with a positive correlation between HARI and NAFLD fibrosis score. Conventional Doppler US can be helpful to detect NAFLD patients with the risk of fibrous tissue accumulation. HARI tends to exceed the range of controls for patients with NAFLD fibrosis score greater than 0.675. The detection of HARI greater than 0.9 in NAFLD patients, regardless of the US degree of severity of steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may be expression of lower risk, which does not necessitate any biopsy.

Comparison of anthropometric measurements in children to predict metabolic syndrome in adolescence: analysis of prospective cohort data.

PubMed

Wicklow, B A; Becker, A; Chateau, D; Palmer, K; Kozyrskij, A; Sellers, E A C

2015-07-01

The optimal screening measures for obesity in children remain controversial. Our study aimed to determine the anthropometric measurement at age 10 years that most strongly predicts the incidence of cardio-metabolic risk factors at age 13 years. This was a prospective cohort study of a population-based cohort of 438 children followed between age 7 and 13 years of age. The main exposure variables were adiposity at age 10 years determined from body mass index (BMI) Z-score, waist circumference (WC) Z-score, waist-to-hip ratio and waist-to-height ratio. Outcome measures included systolic (SBP) and diastolic blood pressure (DBP), fasting high-density (HDL-c) and low-density lipoprotein cholesterol (LDL-c), triglycerides, insulin and glucose (homeostasis model of assessment, HOMA), and the presence of metabolic syndrome (MetS). WC Z-score at age 10 years was a stronger predictor of SBP (β 0.21, R(2) 0.38, P<0.001 vs β 0.30, R(2) 0.20, P<0.001) and HOMA (β 0.51, R(2) 0.25, P<0.001 vs 0.40, R(2) 0.19, P<0.001) at age 13 years compared with BMI Z-score. WC relative to height and hip was stronger predictors of cardio- metabolic risk than BMI Z-score or WC Z-score. The relative risk (RR) of incident MetS was greater for an elevated BMI Z-score than for an elevated WC (girls: RR 2.52, 95% confidence interval (CI): 1.46-4.34 vs RR 1.56, 95% CI 1.18-2.07) and (boys: RR 2.86, 95% CI 1.79-4.62 vs RR 2.09, 95% CI 1.59-2.77). WC was a better predictor of SBP and HOMA compared with BMI or WC expressed relative to height or hip circumference. BMI was associated with higher odds of MetS compared with WC. Thus, BMI and WC may each be clinically relevant markers of different cardio-metabolic risk factors, and important in informing obesity-related prevention and treatment strategies.

[Non-invasive fibrosis indexes in predicting acute liver function deterioration after transcatheter arterial chemoembolization].

PubMed

Song, Y P; Zhao, Q Y; Li, S; Wang, H; Wu, P H

2016-03-08

To investigate the ability of two non-invasive fibrosis indexes-APRI, i. e. aspartate transaminase (AST) to platelet (PLT) ratio index, and fibrosis index based on the 4 factors (FIB-4)score in predicting ALFD in patients with unresectable primary HCC and underwent TACE. Clinical data of those patients treated with TACE in Department of Interventional Radiology of the Center from Jan 2010 to Aug 2014 were investigated retrospectively. A total of 366 cases were enrolled after randomized selection, 62 (18.5%) of which developed ALFD after TACE. Child-Pugh score, APRI and FIB-4 score in every case were calculated, receiver operating characteristic (ROC) curve of each model were performed and the predictive abilities of them were assessed by area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity. The AUC of Child-Pugh score, APRI and FIB-4 score were 0.783, 0.752 and 0.758 respectively, while the difference had no significance in statistics, indicating that predictive accuracies of them were similar. APRI≤1.15 and FIB-4≤3.08 had better NPV (90.6% and 93.6%) and sensitivity (65.6% and 80.0%) than Child-Pugh score>6 (NPV=85.8%, sensitivity=27.4%), PPV and specificity of them are 35.7%, 32.9%, 89.5% and 73.7%, 64.2%, 99.3% respectively. Comparing to Child-Pugh score, APRI and FIB-4 score have similar accuracy but better NPV and sensitivity in predicting post-TACE ALFD. Thereafter they are good for selection of low-risk patients for TACE treatment. Candidates with an APRI≤1.15 or a FIB-4≤3.08 or in Child-Pugh a stage are unlikely to develop ALFD thus could receive TACE safely.

The Novel Scoring System for 30-Day Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding.

PubMed

Hwang, Sejin; Jeon, Seong Woo; Kwon, Joong Goo; Lee, Dong Wook; Ha, Chang Yoon; Cho, Kwang Bum; Jang, ByungIk; Park, Jung Bae; Park, Youn Sun

2016-07-01

Although the mortality rates for non-variceal upper gastrointestinal bleeding (NVUGIB) have recently decreased, it remains a significant medical problem. The main aim of this prospective multicenter database study was to construct a clinically useful predictive scoring system by using our predictors and compare its prognostic accuracy with that of the Rockall scoring system. Data were collected from consecutive patients with NVUGIB. Logistic regression analysis was performed to identify the independent predictors of 30-day mortality. Each independent predictor was assigned an integral point proportional to the odds ratio (OR) and we used the area under the curve to compare the discrimination ability between the new predictive model and the Rockall score. The independent predictors of mortality included age >65 years [OR 2.627; 95 % confidence interval (CI) 1.298-5.318], hemodynamic instability (OR 2.217; 95 % CI 1.069-4.597), serum blood urea nitrogen level >40 mg/dL (OR 1.895; 95 % CI 1.029-3.490), active bleeding at endoscopy (OR 2.434; 95 % CI 1.283-4.616), transfusions (OR 3.811; 95 % CI 1.640-8.857), comorbidities (OR 3.481; 95 % CI 1.405-8.624), and rebleeding (OR 10.581; 95 % CI 5.590-20.030). The new predictive model showed a high discrimination capability and was significantly superior to the Rockall score in predicting the risk of death (OR 0.837;95 % CI 0.818-0.855 vs. 0.761; 0.739-0.782; P = 0.0123). The new predictive score was significantly more accurate than the Rockall score in predicting death in NVUGIB patients. We need to prospectively validate the accuracy of this score for predicting mortality in NVUGIB patients.

The novel EuroSCORE II algorithm predicts the hospital mortality of thoracic aortic surgery in 461 consecutive Japanese patients better than both the original additive and logistic EuroSCORE algorithms.

PubMed

Nishida, Takahiro; Sonoda, Hiromichi; Oishi, Yasuhisa; Tanoue, Yoshihisa; Nakashima, Atsuhiro; Shiokawa, Yuichi; Tominaga, Ryuji

2014-04-01

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was developed to improve the overestimation of surgical risk associated with the original (additive and logistic) EuroSCOREs. The purpose of this study was to evaluate the significance of the EuroSCORE II by comparing its performance with that of the original EuroSCOREs in Japanese patients undergoing surgery on the thoracic aorta. We have calculated the predicted mortalities according to the additive EuroSCORE, logistic EuroSCORE and EuroSCORE II algorithms in 461 patients who underwent surgery on the thoracic aorta during a period of 20 years (1993-2013). The actual in-hospital mortality rates in the low- (additive EuroSCORE of 3-6), moderate- (7-11) and high-risk (≥11) groups (followed by overall mortality) were 1.3, 6.2 and 14.4% (7.2% overall), respectively. Among the three different risk groups, the expected mortality rates were 5.5 ± 0.6, 9.1 ± 0.7 and 13.5 ± 0.2% (9.5 ± 0.1% overall) by the additive EuroSCORE algorithm, 5.3 ± 0.1, 16 ± 0.4 and 42.4 ± 1.3% (19.9 ± 0.7% overall) by the logistic EuroSCORE algorithm and 1.6 ± 0.1, 5.2 ± 0.2 and 18.5 ± 1.3% (7.4 ± 0.4% overall) by the EuroSCORE II algorithm, indicating poor prediction (P < 0.0001) of the mortality in the high-risk group, especially by the logistic EuroSCORE. The areas under the receiver operating characteristic curves of the additive EuroSCORE, logistic EuroSCORE and EuroSCORE II algorithms were 0.6937, 0.7169 and 0.7697, respectively. Thus, the mortality expected by the EuroSCORE II more closely matched the actual mortality in all three risk groups. In contrast, the mortality expected by the logistic EuroSCORE overestimated the risks in the moderate- (P = 0.0002) and high-risk (P < 0.0001) patient groups. Although all of the original EuroSCOREs and EuroSCORE II appreciably predicted the surgical mortality for thoracic aortic surgery in Japanese patients, the EuroSCORE II best predicted the mortalities in all risk groups.

Significance of DNA Replication Licensing Proteins (MCM2, MCM5 and CDC6), p16 and p63 as Markers of Premalignant Lesions of the Uterine Cervix: Its Usefulness to Predict Malignant Potential

PubMed Central

Saritha, VN; Veena, VS; Krishna, KM Jagathnath; Somanathan, Thara; Sujathan, K

2018-01-01

Cervical cancer continues to be a leading cancer among women in many parts of the world. Nation-wide screening with the Pap smear has not been implemented in India due to the lack of adequately trained cytologists. Identification of biomarkers to predict malignant potential of the identified low risk lesions is essential to avoid excessive retesting and follow up. The current study analyzed the expression patterns of DNA replication licensing proteins, proliferation inhibitor protein p16INK4A and tumor suppresser protein p63 in cervical tissues and smears to assess the ability of these proteins to predict progression. Methods: Cervical smears and corresponding tissues were immunostained using mouse monoclonal antibodies against MCM2, MCM5, CDC6, p16 and p63. Smears were treated with a non-ionic surfactant sodium deoxycholate prior to immuno-cytochemistry. The standard ABC method of immunohistochemistry was performed using DAB as the chromogen. The immunostained samples were scored on a 0-3+ scale and staining patterns of smears were compared with those of tissue sections. Sensitivity and specificity for each of these markers were calculated taking histopathology as the gold standard. Result: All the markers were positive in malignant and dysplastic cells. MCM protein expression was found to be up-regulated in LSIL, HSIL and in malignancies to a greater extent than p16 as well as p63. CDC6 protein was preferentially expressed in high grade lesions and in invasive squamous cell carcinomas. A progressive increase in the expression of DNA replication licensing proteins in accordance with the grades of cervical intraepithelial lesion suggests these markers as significant to predict malignant potential of low grade lesions in cervical smears. Conclusion: MCMs and CDC6 can be applied as biomarkers to predict malignant potential of low grade lesions identified in screening programmes and retesting / follow up might be confined to those with high risk lesions alone so that overuse of resources can be safely avoided. PMID:29373905

Relationship between COMLEX-USA scores and performance on the American Osteopathic Board of Emergency Medicine Part I certifying examination.

PubMed

Li, Feiming; Gimpel, John R; Arenson, Ethan; Song, Hao; Bates, Bruce P; Ludwin, Fredric

2014-04-01

Few studies have investigated how well scores from the Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) series predict resident outcomes, such as performance on board certification examinations. To determine how well COMLEX-USA predicts performance on the American Osteopathic Board of Emergency Medicine (AOBEM) Part I certification examination. The target study population was first-time examinees who took AOBEM Part I in 2011 and 2012 with matched performances on COMLEX-USA Level 1, Level 2-Cognitive Evaluation (CE), and Level 3. Pearson correlations were computed between AOBEM Part I first-attempt scores and COMLEX-USA performances to measure the association between these examinations. Stepwise linear regression analysis was conducted to predict AOBEM Part I scores by the 3 COMLEX-USA scores. An independent t test was conducted to compare mean COMLEX-USA performances between candidates who passed and who failed AOBEM Part I, and a stepwise logistic regression analysis was used to predict the log-odds of passing AOBEM Part I on the basis of COMLEX-USA scores. Scores from AOBEM Part I had the highest correlation with COMLEX-USA Level 3 scores (.57) and slightly lower correlation with COMLEX-USA Level 2-CE scores (.53). The lowest correlation was between AOBEM Part I and COMLEX-USA Level 1 scores (.47). According to the stepwise regression model, COMLEX-USA Level 1 and Level 2-CE scores, which residency programs often use as selection criteria, together explained 30% of variance in AOBEM Part I scores. Adding Level 3 scores explained 37% of variance. The independent t test indicated that the 397 examinees passing AOBEM Part I performed significantly better than the 54 examinees failing AOBEM Part I in all 3 COMLEX-USA levels (P<.001 for all 3 levels). The logistic regression model showed that COMLEX-USA Level 1 and Level 3 scores predicted the log-odds of passing AOBEM Part I (P=.03 and P<.001, respectively). The present study empirically supported the predictive and discriminant validities of the COMLEX-USA series in relation to the AOBEM Part I certification examination. Although residency programs may use COMLEX-USA Level 1 and Level 2-CE scores as partial criteria in selecting residents, Level 3 scores, though typically not available at the time of application, are actually the most statistically related to performances on AOBEM Part I.

Framework for making better predictions by directly estimating variables' predictivity.

PubMed

Lo, Adeline; Chernoff, Herman; Zheng, Tian; Lo, Shaw-Hwa

2016-12-13

We propose approaching prediction from a framework grounded in the theoretical correct prediction rate of a variable set as a parameter of interest. This framework allows us to define a measure of predictivity that enables assessing variable sets for, preferably high, predictivity. We first define the prediction rate for a variable set and consider, and ultimately reject, the naive estimator, a statistic based on the observed sample data, due to its inflated bias for moderate sample size and its sensitivity to noisy useless variables. We demonstrate that the [Formula: see text]-score of the PR method of VS yields a relatively unbiased estimate of a parameter that is not sensitive to noisy variables and is a lower bound to the parameter of interest. Thus, the PR method using the [Formula: see text]-score provides an effective approach to selecting highly predictive variables. We offer simulations and an application of the [Formula: see text]-score on real data to demonstrate the statistic's predictive performance on sample data. We conjecture that using the partition retention and [Formula: see text]-score can aid in finding variable sets with promising prediction rates; however, further research in the avenue of sample-based measures of predictivity is much desired.

Framework for making better predictions by directly estimating variables’ predictivity

PubMed Central

Chernoff, Herman; Lo, Shaw-Hwa

2016-01-01

We propose approaching prediction from a framework grounded in the theoretical correct prediction rate of a variable set as a parameter of interest. This framework allows us to define a measure of predictivity that enables assessing variable sets for, preferably high, predictivity. We first define the prediction rate for a variable set and consider, and ultimately reject, the naive estimator, a statistic based on the observed sample data, due to its inflated bias for moderate sample size and its sensitivity to noisy useless variables. We demonstrate that the I-score of the PR method of VS yields a relatively unbiased estimate of a parameter that is not sensitive to noisy variables and is a lower bound to the parameter of interest. Thus, the PR method using the I-score provides an effective approach to selecting highly predictive variables. We offer simulations and an application of the I-score on real data to demonstrate the statistic’s predictive performance on sample data. We conjecture that using the partition retention and I-score can aid in finding variable sets with promising prediction rates; however, further research in the avenue of sample-based measures of predictivity is much desired. PMID:27911830

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

PubMed

Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Neale, Benjamin M; Davis, Lea K; Gamazon, Eric R; Derks, Eske M; Evans, Patrick; Edlund, Christopher K; Crane, Jacquelyn; Fagerness, Jesen A; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Brentani, Helena; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond D; Cappi, Carolina; Silgado, Julio C Cardona; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Cook, Edwin H; Cookson, M R; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L; Girard, Simon L; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hezel, Dianne M; Hoekstra, Pieter J; Jankovic, Joseph; Kennedy, James L; King, Robert A; Konkashbaev, Anuar I; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T; Mesa Restrepo, Sandra C; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L; Naarden, Allan L; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L; Renner, Tobias; Reus, Victor I; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Romero, Roxana; Rosário, Maria C; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Service, Susan K; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H; Stein, Dan J; Strengman, Eric; Tischfield, Jay A; Turiel, Maurizio; Valencia Duarte, Ana V; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R; Westenberg, Herman G M; Shugart, Yin Yao; Hounie, Ana G; Miguel, Euripedes C; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C; McMahon, William; Posthuma, Danielle; Oostra, Ben A; Nestadt, Gerald; Rouleau, Guy A; Purcell, Shaun; Jenike, Michael A; Heutink, Peter; Hanna, Gregory L; Conti, David V; Arnold, Paul D; Freimer, Nelson B; Stewart, S Evelyn; Knowles, James A; Cox, Nancy J; Pauls, David L

2015-01-01

Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy.

PubMed

Esteva, Francisco J; Sahin, Aysegul A; Cristofanilli, Massimo; Coombes, Kevin; Lee, Sang-Joon; Baker, Joffre; Cronin, Maureen; Walker, Michael; Watson, Drew; Shak, Steven; Hortobagyi, Gabriel N

2005-05-01

To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-microm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.

Prediction of distal residue participation in enzyme catalysis

PubMed Central

Brodkin, Heather R; DeLateur, Nicholas A; Somarowthu, Srinivas; Mills, Caitlyn L; Novak, Walter R; Beuning, Penny J; Ringe, Dagmar; Ondrechen, Mary Jo

2015-01-01

A scoring method for the prediction of catalytically important residues in enzyme structures is presented and used to examine the participation of distal residues in enzyme catalysis. Scores are based on the Partial Order Optimum Likelihood (POOL) machine learning method, using computed electrostatic properties, surface geometric features, and information obtained from the phylogenetic tree as input features. Predictions of distal residue participation in catalysis are compared with experimental kinetics data from the literature on variants of the featured enzymes; some additional kinetics measurements are reported for variants of Pseudomonas putida nitrile hydratase (ppNH) and for Escherichia coli alkaline phosphatase (AP). The multilayer active sites of P. putida nitrile hydratase and of human phosphoglucose isomerase are predicted by the POOL log ZP scores, as is the single-layer active site of P. putida ketosteroid isomerase. The log ZP score cutoff utilized here results in over-prediction of distal residue involvement in E. coli alkaline phosphatase. While fewer experimental data points are available for P. putida mandelate racemase and for human carbonic anhydrase II, the POOL log ZP scores properly predict the previously reported participation of distal residues. PMID:25627867

Detecting determinism with improved sensitivity in time series: rank-based nonlinear predictability score.

PubMed

Naro, Daniel; Rummel, Christian; Schindler, Kaspar; Andrzejak, Ralph G

2014-09-01

The rank-based nonlinear predictability score was recently introduced as a test for determinism in point processes. We here adapt this measure to time series sampled from time-continuous flows. We use noisy Lorenz signals to compare this approach against a classical amplitude-based nonlinear prediction error. Both measures show an almost identical robustness against Gaussian white noise. In contrast, when the amplitude distribution of the noise has a narrower central peak and heavier tails than the normal distribution, the rank-based nonlinear predictability score outperforms the amplitude-based nonlinear prediction error. For this type of noise, the nonlinear predictability score has a higher sensitivity for deterministic structure in noisy signals. It also yields a higher statistical power in a surrogate test of the null hypothesis of linear stochastic correlated signals. We show the high relevance of this improved performance in an application to electroencephalographic (EEG) recordings from epilepsy patients. Here the nonlinear predictability score again appears of higher sensitivity to nonrandomness. Importantly, it yields an improved contrast between signals recorded from brain areas where the first ictal EEG signal changes were detected (focal EEG signals) versus signals recorded from brain areas that were not involved at seizure onset (nonfocal EEG signals).

Detecting determinism with improved sensitivity in time series: Rank-based nonlinear predictability score

NASA Astrophysics Data System (ADS)

Naro, Daniel; Rummel, Christian; Schindler, Kaspar; Andrzejak, Ralph G.

2014-09-01

The rank-based nonlinear predictability score was recently introduced as a test for determinism in point processes. We here adapt this measure to time series sampled from time-continuous flows. We use noisy Lorenz signals to compare this approach against a classical amplitude-based nonlinear prediction error. Both measures show an almost identical robustness against Gaussian white noise. In contrast, when the amplitude distribution of the noise has a narrower central peak and heavier tails than the normal distribution, the rank-based nonlinear predictability score outperforms the amplitude-based nonlinear prediction error. For this type of noise, the nonlinear predictability score has a higher sensitivity for deterministic structure in noisy signals. It also yields a higher statistical power in a surrogate test of the null hypothesis of linear stochastic correlated signals. We show the high relevance of this improved performance in an application to electroencephalographic (EEG) recordings from epilepsy patients. Here the nonlinear predictability score again appears of higher sensitivity to nonrandomness. Importantly, it yields an improved contrast between signals recorded from brain areas where the first ictal EEG signal changes were detected (focal EEG signals) versus signals recorded from brain areas that were not involved at seizure onset (nonfocal EEG signals).

Development of a novel score for the prediction of hospital mortality in patients with severe sepsis: the use of electronic healthcare records with LASSO regression.

PubMed

Zhang, Zhongheng; Hong, Yucai

2017-07-25

There are several disease severity scores being used for the prediction of mortality in critically ill patients. However, none of them was developed and validated specifically for patients with severe sepsis. The present study aimed to develop a novel prediction score for severe sepsis. A total of 3206 patients with severe sepsis were enrolled, including 1054 non-survivors and 2152 survivors. The LASSO score showed the best discrimination (area under curve: 0.772; 95% confidence interval: 0.735-0.810) in the validation cohort as compared with other scores such as simplified acute physiology score II, acute physiological score III, Logistic organ dysfunction system, sequential organ failure assessment score, and Oxford Acute Severity of Illness Score. The calibration slope was 0.889 and Brier value was 0.173. The study employed a single center database called Medical Information Mart for Intensive Care-III) MIMIC-III for analysis. Severe sepsis was defined as infection and acute organ dysfunction. Clinical and laboratory variables used in clinical routines were included for screening. Subjects without missing values were included, and the whole dataset was split into training and validation cohorts. The score was coined LASSO score because variable selection was performed using the least absolute shrinkage and selection operator (LASSO) technique. Finally, the LASSO score was evaluated for its discrimination and calibration in the validation cohort. The study developed the LASSO score for mortality prediction in patients with severe sepsis. Although the score had good discrimination and calibration in a randomly selected subsample, external validations are still required.

Expressing Anger Is More Dangerous than Feeling Angry when Driving

PubMed Central

Qu, Weina; Dai, Mengnuo; Zhao, Wenguo; Zhang, Kan

2016-01-01

Anger is an emotion that drivers often feel and express while driving, and it is believed by researchers to be an important cause of dangerous driving behavior. In this study, the relationships between driving trait anger, driving anger expression, and dangerous driving behaviors were analyzed. The Driving Anger Scale (DAS) was used to measure driving trait anger, whereas the Driving Anger Expression (DAX) Inventory was used to measure expressions of driving anger. A sample of 38 drivers completed the DAS, DAX, and a driving simulation session on a simulator where their driving behaviors were recorded. Correlation analysis showed that the higher scores on the DAS were associated with longer durations of speeding in the simulator. The more participants expressed their anger in verbal and physical ways, the more likely they were to crash the virtual vehicle during the simulation. Regression analyses illustrated the same pattern. The findings suggest that, although trait anger is related to speeding, the passive expression of anger is the real factor underling traffic accidents. This study extends findings about the predictive effects of self-report scales of driving behaviors to behaviors recorded on a simulator. Thus, if in traffic safety propaganda, guiding drivers to use positive ways to cope with driving anger is recommended by our findings. PMID:27258144

Expressing Anger Is More Dangerous than Feeling Angry when Driving.

PubMed

Qu, Weina; Dai, Mengnuo; Zhao, Wenguo; Zhang, Kan; Ge, Yan

2016-01-01

Anger is an emotion that drivers often feel and express while driving, and it is believed by researchers to be an important cause of dangerous driving behavior. In this study, the relationships between driving trait anger, driving anger expression, and dangerous driving behaviors were analyzed. The Driving Anger Scale (DAS) was used to measure driving trait anger, whereas the Driving Anger Expression (DAX) Inventory was used to measure expressions of driving anger. A sample of 38 drivers completed the DAS, DAX, and a driving simulation session on a simulator where their driving behaviors were recorded. Correlation analysis showed that the higher scores on the DAS were associated with longer durations of speeding in the simulator. The more participants expressed their anger in verbal and physical ways, the more likely they were to crash the virtual vehicle during the simulation. Regression analyses illustrated the same pattern. The findings suggest that, although trait anger is related to speeding, the passive expression of anger is the real factor underling traffic accidents. This study extends findings about the predictive effects of self-report scales of driving behaviors to behaviors recorded on a simulator. Thus, if in traffic safety propaganda, guiding drivers to use positive ways to cope with driving anger is recommended by our findings.

A machine learning approach to predicting protein-ligand binding affinity with applications to molecular docking.

PubMed

Ballester, Pedro J; Mitchell, John B O

2010-05-01

Accurately predicting the binding affinities of large sets of diverse protein-ligand complexes is an extremely challenging task. The scoring functions that attempt such computational prediction are essential for analysing the outputs of molecular docking, which in turn is an important technique for drug discovery, chemical biology and structural biology. Each scoring function assumes a predetermined theory-inspired functional form for the relationship between the variables that characterize the complex, which also include parameters fitted to experimental or simulation data and its predicted binding affinity. The inherent problem of this rigid approach is that it leads to poor predictivity for those complexes that do not conform to the modelling assumptions. Moreover, resampling strategies, such as cross-validation or bootstrapping, are still not systematically used to guard against the overfitting of calibration data in parameter estimation for scoring functions. We propose a novel scoring function (RF-Score) that circumvents the need for problematic modelling assumptions via non-parametric machine learning. In particular, Random Forest was used to implicitly capture binding effects that are hard to model explicitly. RF-Score is compared with the state of the art on the demanding PDBbind benchmark. Results show that RF-Score is a very competitive scoring function. Importantly, RF-Score's performance was shown to improve dramatically with training set size and hence the future availability of more high-quality structural and interaction data is expected to lead to improved versions of RF-Score. pedro.ballester@ebi.ac.uk; jbom@st-andrews.ac.uk Supplementary data are available at Bioinformatics online.

Predictive values of D-dimer assay, GRACE scores and TIMI scores for adverse outcome in patients with non-ST-segment elevation myocardial infarction

PubMed Central

Satilmisoglu, Muhammet Hulusi; Ozyilmaz, Sinem Ozbay; Gul, Mehmet; Ak Yildirim, Hayriye; Kayapinar, Osman; Gokturk, Kadir; Aksu, Huseyin; Erkanli, Korhan; Eksik, Abdurrahman

2017-01-01

Purpose To determine the predictive values of D-dimer assay, Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk scores for adverse outcome in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Patients and methods A total of 234 patients (mean age: 57.2±11.7 years, 75.2% were males) hospitalized with NSTEMI were included. Data on D-dimer assay, GRACE and TIMI risk scores were recorded. Logistic regression analysis was conducted to determine the risk factors predicting increased mortality. Results Median D-dimer levels were 349.5 (48.0–7,210.0) ng/mL, the average TIMI score was 3.2±1.2 and the GRACE score was 90.4±27.6 with high GRACE scores (>118) in 17.5% of patients. The GRACE score was correlated positively with both the D-dimer assay (r=0.215, P=0.01) and TIMI scores (r=0.504, P=0.000). Multivariate logistic regression analysis revealed that higher creatinine levels (odds ratio =18.465, 95% confidence interval: 1.059–322.084, P=0.046) constituted the only significant predictor of increased mortality risk with no predictive values for age, D-dimer assay, ejection fraction, glucose, hemoglobin A1c, sodium, albumin or total cholesterol levels for mortality. Conclusion Serum creatinine levels constituted the sole independent determinant of mortality risk, with no significant values for D-dimer assay, GRACE or TIMI scores for predicting the risk of mortality in NSTEMI patients. PMID:28408834

The effect of obesity on the rate of heparin-induced thrombocytopenia.

PubMed

Marler, Jacob L; Jones, G Morgan; Wheeler, Brian J; Alshaya, Abdulrahman; Hartmann, Jonathan L; Oliphant, Carrie S

2018-06-01

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

Operating Comfort Prediction Model of Human-Machine Interface Layout for Cabin Based on GEP.

PubMed

Deng, Li; Wang, Guohua; Chen, Bo

2015-01-01

In view of the evaluation and decision-making problem of human-machine interface layout design for cabin, the operating comfort prediction model is proposed based on GEP (Gene Expression Programming), using operating comfort to evaluate layout scheme. Through joint angles to describe operating posture of upper limb, the joint angles are taken as independent variables to establish the comfort model of operating posture. Factor analysis is adopted to decrease the variable dimension; the model's input variables are reduced from 16 joint angles to 4 comfort impact factors, and the output variable is operating comfort score. The Chinese virtual human body model is built by CATIA software, which will be used to simulate and evaluate the operators' operating comfort. With 22 groups of evaluation data as training sample and validation sample, GEP algorithm is used to obtain the best fitting function between the joint angles and the operating comfort; then, operating comfort can be predicted quantitatively. The operating comfort prediction result of human-machine interface layout of driller control room shows that operating comfort prediction model based on GEP is fast and efficient, it has good prediction effect, and it can improve the design efficiency.

Operating Comfort Prediction Model of Human-Machine Interface Layout for Cabin Based on GEP

PubMed Central

Wang, Guohua; Chen, Bo

2015-01-01

In view of the evaluation and decision-making problem of human-machine interface layout design for cabin, the operating comfort prediction model is proposed based on GEP (Gene Expression Programming), using operating comfort to evaluate layout scheme. Through joint angles to describe operating posture of upper limb, the joint angles are taken as independent variables to establish the comfort model of operating posture. Factor analysis is adopted to decrease the variable dimension; the model's input variables are reduced from 16 joint angles to 4 comfort impact factors, and the output variable is operating comfort score. The Chinese virtual human body model is built by CATIA software, which will be used to simulate and evaluate the operators' operating comfort. With 22 groups of evaluation data as training sample and validation sample, GEP algorithm is used to obtain the best fitting function between the joint angles and the operating comfort; then, operating comfort can be predicted quantitatively. The operating comfort prediction result of human-machine interface layout of driller control room shows that operating comfort prediction model based on GEP is fast and efficient, it has good prediction effect, and it can improve the design efficiency. PMID:26448740

Evaluation of prenatal risk factors for prediction of outcome in right heart lesions: CVP score in fetal right heart defects.

PubMed

Neves, Ana Luisa; Mathias, Leigh; Wilhm, Marilyn; Leshko, Jennifer; Linask, Kersti K; Henriques-Coelho, Tiago; Areias, José C; Huhta, James C

2014-09-01

To determine the prenatal variables predicting the risk of perinatal death in congenital right heart defects. Retrospective analysis of 28 fetuses with right heart defects was performed. Logistic regression analyses were performed to obtain odds ratios (OR) for the relationship between the risk of death and echocardiographic parameters. The parameters that correlated with the outcome were incorporated in an attempt to devise a disease-specific cardiovascular profile score. Fetal echocardiograms (143) from 28 patients were analyzed. The cardiovascular profile score predicted the risk of death. A lower right ventricle (RV) pressure was associated with mortality (OR 0.959; 95% confidence intervals (CI) 0.940-0.978). Higher peak aortic velocity through the aortic valve (OR 0.104; 95% CI 0.020-0.529) was associated with a better outcome. These cardiac function parameters were incorporated in a modified disease-specific CVP Score. Patients with a mean modified cardiovascular profile score of ≤ 6 were over 3.7 times more likely to die than those with scores of 7-10. The original Cardiovascular Profile Score predicted the risk of death in right heart defects. The modified score was not validated as a good prediction tool by this study. Fetal RV pressure estimate and peak aortic velocity can be used as independent prognostic predictors.

Similar predictions of etravirine sensitivity regardless of genotypic testing method used: comparison of available scoring systems.

PubMed

Vingerhoets, Johan; Nijs, Steven; Tambuyzer, Lotke; Hoogstoel, Annemie; Anderson, David; Picchio, Gaston

2012-01-01

The aims of this study were to compare various genotypic scoring systems commonly used to predict virological outcome to etravirine, and examine their concordance with etravirine phenotypic susceptibility. Six etravirine genotypic scoring systems were assessed: Tibotec 2010 (based on 20 mutations; TBT 20), Monogram, Stanford HIVdb, ANRS, Rega (based on 37, 30, 27 and 49 mutations, respectively) and virco(®)TYPE HIV-1 (predicted fold change based on genotype). Samples from treatment-experienced patients who participated in the DUET trials and with both genotypic and phenotypic data (n=403) were assessed using each scoring system. Results were retrospectively correlated with virological response in DUET. κ coefficients were calculated to estimate the degree of correlation between the different scoring systems. Correlation between the five scoring systems and the TBT 20 system was approximately 90%. Virological response by etravirine susceptibility was comparable regardless of which scoring system was utilized, with 70-74% of DUET patients determined as susceptible to etravirine by the different scoring systems achieving plasma viral load <50 HIV-1 RNA copies/ml. In samples classed as phenotypically susceptible to etravirine (fold change in 50% effective concentration ≤3), correlations with genotypic score were consistently high across scoring systems (≥70%). In general, the etravirine genotypic scoring systems produced similar results, and genotype-phenotype concordance was high. As such, phenotypic interpretations, and in their absence all genotypic scoring systems investigated, may be used to reliably predict the activity of etravirine.

The Dynamics of Self-Esteem in Cognitive Therapy for Avoidant and Obsessive-Compulsive Personality Disorders: An Adaptive Role of Self-Esteem Variability?

PubMed Central

Cummings, Jorden A.; Hayes, Adele M.; Cardaciotto, LeeAnn; Newman, Cory F.

2011-01-01

Self-esteem variability is often associated with poor functioning. However, in disorders with entrenched negative views of self and in a context designed to challenge those views, variable self-esteem might represent a marker of change. We examined self-esteem variability in a sample of 27 patients with Avoidant and Obsessive-Compulsive Personality Disorders who received Cognitive Therapy (CT). A therapy coding system was used to rate patients’ positive and negative views of self expressed in the first ten sessions of a 52-week treatment. Ratings of negative (reverse scored) and positive view of self were summed to create a composite score for each session. Self-esteem variability was calculated as the standard deviation of self-esteem scores across sessions. More self-esteem variability predicted more improvement in personality disorder and depression symptoms at the end of treatment, beyond baseline and average self-esteem. Early variability in self-esteem, in this population and context, appeared to be a marker of therapeutic change. PMID:22923855

Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells

PubMed Central

Zhong, Guocai; Wang, Haimin; Bailey, Charles C; Gao, Guangping; Farzan, Michael

2016-01-01

Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in mammalian systems. Here we describe a rational-design approach that enables rapid development of efficient cis-acting aptazyme riboswitches. We identified communication-module characteristics associated with aptazyme functionality through analysis of a 32-aptazyme test panel. We then developed a scoring system that predicts an aptazymes’s activity by integrating three characteristics of communication-module bases: hydrogen bonding, base stacking, and distance to the enzymatic core. We validated the power and generality of this approach by designing aptazymes responsive to three distinct ligands, each with markedly wider dynamic ranges than any previously reported. These aptayzmes efficiently regulated adeno-associated virus (AAV)-vectored transgene expression in cultured mammalian cells and mice, highlighting one application of these broadly usable regulatory switches. Our approach enables efficient, protein-independent control of gene expression by a range of small molecules. DOI: http://dx.doi.org/10.7554/eLife.18858.001 PMID:27805569

Utility of different cardiovascular disease prediction models in rheumatoid arthritis.

PubMed

Purcarea, A; Sovaila, S; Udrea, G; Rezus, E; Gheorghe, A; Tiu, C; Stoica, V

2014-01-01

Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted.

Utility of different cardiovascular disease prediction models in rheumatoid arthritis

PubMed Central

Purcarea, A; Sovaila, S; Udrea, G; Rezus, E; Gheorghe, A; Tiu, C; Stoica, V

2014-01-01

Background. Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. Methods. In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. Results. In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. Conclusion. The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted. PMID:25713628

Predicting Coronary Artery Aneurysms in Kawasaki Disease at a North American Center: An Assessment of Baseline z Scores.

PubMed

Son, Mary Beth F; Gauvreau, Kimberlee; Kim, Susan; Tang, Alexander; Dedeoglu, Fatma; Fulton, David R; Lo, Mindy S; Baker, Annette L; Sundel, Robert P; Newburger, Jane W

2017-05-31

Accurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area ( z scores) for future CAAs in Kawasaki disease and explored the extent to which addition of established Japanese risk scores to baseline coronary artery z scores improved discrimination for CAA development. We explored the relationships of CAA with baseline z scores; with Kobayashi, Sano, Egami, and Harada risk scores; and with the combination of baseline z scores and risk scores. We defined CAA as a maximum z score (zMax) ≥2.5 of the left anterior descending or right coronary artery at 4 to 8 weeks of illness. Of 261 patients, 77 patients (29%) had a baseline zMax ≥2.0. CAAs occurred in 15 patients (6%). CAAs were strongly associated with baseline zMax ≥2.0 versus <2.0 (12 [16%] versus 3 [2%], respectively, P <0.001). Baseline zMax ≥2.0 had a C statistic of 0.77, good sensitivity (80%), and excellent negative predictive value (98%). None of the risk scores alone had adequate discrimination. When high-risk status per the Japanese risk scores was added to models containing baseline zMax ≥2.0, none were significantly better than baseline zMax ≥2.0 alone. In a North American center, baseline zMax ≥2.0 in children with Kawasaki disease demonstrated high predictive utility for later development of CAA. Future studies should validate the utility of our findings. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Measurement Error and Bias in Value-Added Models. Research Report. ETS RR-17-25

ERIC Educational Resources Information Center

Kane, Michael T.

2017-01-01

By aggregating residual gain scores (the differences between each student's current score and a predicted score based on prior performance) for a school or a teacher, value-added models (VAMs) can be used to generate estimates of school or teacher effects. It is known that random errors in the prior scores will introduce bias into predictions of…

Development and validation of an endoscopic classification of diverticular disease of the colon: the DICA classification.

PubMed

Tursi, Antonio; Brandimarte, Giovanni; Di Mario, Francesco; Andreoli, Arnaldo; Annunziata, Maria Laura; Astegiano, Marco; Bianco, Maria Antonietta; Buri, Luigi; Cammarota, Giovanni; Capezzuto, Erminio; Chilovi, Fausto; Cianci, Massimo; Conigliaro, Rita; Del Favero, Giuseppe; Di Cesare, Luigi; Di Fonzo, Michela; Elisei, Walter; Faggiani, Roberto; Farroni, Ferruccio; Forti, Giacomo; Germanà, Bastianello; Giorgetti, Gian Marco; Giovannone, Maurizio; Lecca, Piera Giuseppina; Loperfido, Silvano; Marmo, Riccardo; Morucci, Piero; Occhigrossi, Giuseppe; Penna, Antonio; Rossi, Alfredo Francesco; Spadaccini, Antonio; Zampaletta, Costantino; Zilli, Maurizio; Zullo, Angelo; Scarpignato, Carmelo; Picchio, Marcello

2015-01-01

A validated endoscopic classification of diverticular disease (DD) of the colon is lacking at present. Our aim was to develop a simple endoscopic score of DD: the Diverticular Inflammation and Complication Assessment (DICA) score. The DICA score for DD resulted in the sum of the scores for the extension of diverticulosis, the number of diverticula per region, the presence and type of inflammation, and the presence and type of complications: DICA 1 (≤ 3), DICA 2 (4-7) and DICA 3 (>7). A comparison with abdominal pain and inflammatory marker expression was also performed. A total of 50 videos of DD patients were reassessed in order to investigate the predictive role of DICA on the outcome of the disease. Overall agreement in using DICA was 0.847 (95% confidence interval, CI, 0.812-0.893): 0.878 (95% CI 0.832-0.895) for DICA 1, 0.765 (95% CI 0.735-0.786) for DICA 2 and 0.891 (95% CI 0.845-0.7923) for DICA 3. Intra-observer agreement (kappa) was 0.91 (95% CI 0.886-0.947). A significant correlation was found between the DICA score and C-reactive protein values (p = 0.0001), as well as between the median pain score and the DICA score (p = 0.0001). With respect to the 50 patients retrospectively reassessed, occurrence/recurrence of disease complications was recorded in 29 patients (58%): 10 (34.5%) were classified as DICA 1 and 19 (65.5%) as DICA 2 (p = 0.036). The DICA score is a simple, reproducible, validated and easy-to-use endoscopic scoring system for DD of the colon. © 2014 S. Karger AG, Basel.

scoringRules - A software package for probabilistic model evaluation

NASA Astrophysics Data System (ADS)

Lerch, Sebastian; Jordan, Alexander; Krüger, Fabian

2016-04-01

Models in the geosciences are generally surrounded by uncertainty, and being able to quantify this uncertainty is key to good decision making. Accordingly, probabilistic forecasts in the form of predictive distributions have become popular over the last decades. With the proliferation of probabilistic models arises the need for decision theoretically principled tools to evaluate the appropriateness of models and forecasts in a generalized way. Various scoring rules have been developed over the past decades to address this demand. Proper scoring rules are functions S(F,y) which evaluate the accuracy of a forecast distribution F , given that an outcome y was observed. As such, they allow to compare alternative models, a crucial ability given the variety of theories, data sources and statistical specifications that is available in many situations. This poster presents the software package scoringRules for the statistical programming language R, which contains functions to compute popular scoring rules such as the continuous ranked probability score for a variety of distributions F that come up in applied work. Two main classes are parametric distributions like normal, t, or gamma distributions, and distributions that are not known analytically, but are indirectly described through a sample of simulation draws. For example, Bayesian forecasts produced via Markov Chain Monte Carlo take this form. Thereby, the scoringRules package provides a framework for generalized model evaluation that both includes Bayesian as well as classical parametric models. The scoringRules package aims to be a convenient dictionary-like reference for computing scoring rules. We offer state of the art implementations of several known (but not routinely applied) formulas, and implement closed-form expressions that were previously unavailable. Whenever more than one implementation variant exists, we offer statistically principled default choices.

Tools for outcome prediction in patients with community acquired pneumonia.

PubMed

Khan, Faheem; Owens, Mark B; Restrepo, Marcos; Povoa, Pedro; Martin-Loeches, Ignacio

2017-02-01

Community-acquired pneumonia (CAP) is one of the most common causes of mortality world-wide. The mortality rate of patients with CAP is influenced by the severity of the disease, treatment failure and the requirement for hospitalization and/or intensive care unit (ICU) management, all of which may be predicted by biomarkers and clinical scoring systems. Areas covered: We review the recent literature examining the efficacy of established and newly-developed clinical scores, biological and inflammatory markers such as C-Reactive protein (CRP), procalcitonin (PCT) and Interleukin-6 (IL-6), whether used alone or in conjunction with clinical severity scores to assess the severity of CAP, predict treatment failure, guide acute in-hospital or ICU admission and predict mortality. Expert commentary: The early prediction of treatment failure using clinical scores and biomarkers plays a developing role in improving survival of patients with CAP by identifying high-risk patients requiring hospitalization or ICU admission; and may enable more efficient allocation of resources. However, it is likely that combinations of scoring systems and biomarkers will be of greater use than individual markers. Further larger studies are needed to corroborate the additive value of these markers to clinical prediction scores to provide a safer and more effective assessment tool for clinicians.

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx.

PubMed

Huber, Gerhard F; Züllig, Lena; Soltermann, Alex; Roessle, Matthias; Graf, Nicole; Haerle, Stephan K; Studer, Gabriela; Jochum, Wolfram; Moch, Holger; Stoeckli, Sandro J

2011-06-03

Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease. E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance. pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis. These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx. 2b.

Automated Assessment of Patients' Self-Narratives for Posttraumatic Stress Disorder Screening Using Natural Language Processing and Text Mining.

PubMed

He, Qiwei; Veldkamp, Bernard P; Glas, Cees A W; de Vries, Theo

2017-03-01

Patients' narratives about traumatic experiences and symptoms are useful in clinical screening and diagnostic procedures. In this study, we presented an automated assessment system to screen patients for posttraumatic stress disorder via a natural language processing and text-mining approach. Four machine-learning algorithms-including decision tree, naive Bayes, support vector machine, and an alternative classification approach called the product score model-were used in combination with n-gram representation models to identify patterns between verbal features in self-narratives and psychiatric diagnoses. With our sample, the product score model with unigrams attained the highest prediction accuracy when compared with practitioners' diagnoses. The addition of multigrams contributed most to balancing the metrics of sensitivity and specificity. This article also demonstrates that text mining is a promising approach for analyzing patients' self-expression behavior, thus helping clinicians identify potential patients from an early stage.

Individual differences in individualism and collectivism predict ratings of virtual cities' liveability and environmental quality.

PubMed

Rubin, Mark; Morrison, Tessa

2014-01-01

The present research investigated individual differences in individualism and collectivism as predictors of people's reactions to cities. Psychology undergraduate students (N = 148) took virtual guided tours around historical cities. They then evaluated the cities' liveability and environmental quality and completed measures of individualism and collectivism. Mediation analyses showed that people who scored high in self-responsibility (individualism) rated the cities as more liveable because they perceived them to be richer and better resourced. In contrast, people who scored high in collectivism rated the cities as having a better environmental quality because they perceived them to (1) provide a greater potential for community and social life and (2) allow people to express themselves. These results indicate that people's evaluations of virtual cities are based on the degree to which certain aspects of the cities are perceived to be consistent with individualist and collectivist values.

Elaboration over a Discourse Facilitates Retrieval in Sentence Processing.

PubMed

Troyer, Melissa; Hofmeister, Philip; Kutas, Marta

2016-01-01

Language comprehension requires access to stored knowledge and the ability to combine knowledge in new, meaningful ways. Previous work has shown that processing linguistically more complex expressions ('Texas cattle rancher' vs. 'rancher') leads to slow-downs in reading during initial processing, possibly reflecting effort in combining information. Conversely, when this information must subsequently be retrieved (as in filler-gap constructions), processing is facilitated for more complex expressions, possibly because more semantic cues are available during retrieval. To follow up on this hypothesis, we tested whether information distributed across a short discourse can similarly provide effective cues for retrieval. Participants read texts introducing two referents (e.g., two senators), one of whom was described in greater detail than the other (e.g., 'The Democrat had voted for one of the senators, and the Republican had voted for the other, a man from Ohio who was running for president'). The final sentence (e.g., 'The senator who the {Republican/Democrat}had voted for…') contained a relative clause picking out either the Many-Cue referent (with 'Republican') or the One-Cue referent (with 'Democrat'). We predicted facilitated retrieval (faster reading times) for the Many-Cue condition at the verb region ('had voted for'), where readers could understand that 'The senator' is the object of the verb. As predicted, this pattern was observed at the retrieval region and continued throughout the rest of the sentence. Participants also completed the Author/Magazine Recognition Tests (ART/MRT; Stanovich and West, 1989), providing a proxy for world knowledge. Since higher ART/MRT scores may index (a) greater experience accessing relevant knowledge and/or (b) richer/more highly structured representations in semantic memory, we predicted it would be positively associated with effects of elaboration on retrieval. We did not observe the predicted interaction between ART/MRT scores and Cue condition at the retrieval region, though ART/MRT interacted with Cue condition in other locations in the sentence. In sum, we found that providing more elaborative information over the course of a text can facilitate retrieval for referents, consistent with a framework in which referential elaboration over a discourse and not just local linguistic information directly impacts information retrieval during sentence processing.

MISS-Prot: web server for self/non-self discrimination of protein residue networks in parasites; theory and experiments in Fasciola peptides and Anisakis allergens.

PubMed

González-Díaz, Humberto; Muíño, Laura; Anadón, Ana M; Romaris, Fernanda; Prado-Prado, Francisco J; Munteanu, Cristian R; Dorado, Julián; Sierra, Alejandro Pazos; Mezo, Mercedes; González-Warleta, Marta; Gárate, Teresa; Ubeira, Florencio M

2011-06-01

Infections caused by human parasites (HPs) affect the poorest 500 million people worldwide but chemotherapy has become expensive, toxic, and/or less effective due to drug resistance. On the other hand, many 3D structures in Protein Data Bank (PDB) remain without function annotation. We need theoretical models to quickly predict biologically relevant Parasite Self Proteins (PSP), which are expressed differentially in a given parasite and are dissimilar to proteins expressed in other parasites and have a high probability to become new vaccines (unique sequence) or drug targets (unique 3D structure). We present herein a model for PSPs in eight different HPs (Ascaris, Entamoeba, Fasciola, Giardia, Leishmania, Plasmodium, Trypanosoma, and Toxoplasma) with 90% accuracy for 15 341 training and validation cases. The model combines protein residue networks, Markov Chain Models (MCM) and Artificial Neural Networks (ANN). The input parameters are the spectral moments of the Markov transition matrix for electrostatic interactions associated with the protein residue complex network calculated with the MARCH-INSIDE software. We implemented this model in a new web-server called MISS-Prot (MARCH-INSIDE Scores for Self-Proteins). MISS-Prot was programmed using PHP/HTML/Python and MARCH-INSIDE routines and is freely available at: . This server is easy to use by non-experts in Bioinformatics who can carry out automatic online upload and prediction with 3D structures deposited at PDB (mode 1). We can also study outcomes of Peptide Mass Fingerprinting (PMFs) and MS/MS for query proteins with unknown 3D structures (mode 2). We illustrated the use of MISS-Prot in experimental and/or theoretical studies of peptides from Fasciola hepatica cathepsin proteases or present on 10 Anisakis simplex allergens (Ani s 1 to Ani s 10). In doing so, we combined electrophoresis (1DE), MALDI-TOF Mass Spectroscopy, and MASCOT to seek sequences, Molecular Mechanics + Molecular Dynamics (MM/MD) to generate 3D structures and MISS-Prot to predict PSP scores. MISS-Prot also allows the prediction of PSP proteins in 16 additional species including parasite hosts, fungi pathogens, disease transmission vectors, and biotechnologically relevant organisms.

Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma.

PubMed

Zhao, Hui; Hua, Ye; Dai, Tu; He, Jian; Tang, Min; Fu, Xu; Mao, Liang; Jin, Huihan; Qiu, Yudong

2017-03-01

Microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) cannot be accurately predicted preoperatively. This study aimed to establish a predictive scoring model of MVI in solitary HCC patients without macroscopic vascular invasion. A total of 309 consecutive HCC patients who underwent curative hepatectomy were divided into the derivation (n=206) and validation cohort (n=103). A predictive scoring model of MVI was established according to the valuable predictors in the derivation cohort based on multivariate logistic regression analysis. The performance of the predictive model was evaluated in the derivation and validation cohorts. Preoperative imaging features on CECT, such as intratumoral arteries, non-nodular type of HCC and absence of radiological tumor capsule were independent predictors for MVI. The predictive scoring model was established according to the β coefficients of the 3 predictors. Area under receiver operating characteristic (AUROC) of the predictive scoring model was 0.872 (95% CI, 0.817-0.928) and 0.856 (95% CI, 0.771-0.940) in the derivation and validation cohorts. The positive and negative predictive values were 76.5% and 88.0% in the derivation cohort and 74.4% and 88.3% in the validation cohort. The performance of the model was similar between the patients with tumor size ≤5cm and >5cm in AUROC (P=0.910). The predictive scoring model based on intratumoral arteries, non-nodular type of HCC, and absence of the radiological tumor capsule on preoperative CECT is of great value in the prediction of MVI regardless of tumor size. Copyright © 2017 Elsevier B.V. All rights reserved.

Boundary curves of individual items in the distribution of total depressive symptom scores approximate an exponential pattern in a general population.

PubMed

Tomitaka, Shinichiro; Kawasaki, Yohei; Ide, Kazuki; Akutagawa, Maiko; Yamada, Hiroshi; Furukawa, Toshiaki A; Ono, Yutaka

2016-01-01

Previously, we proposed a model for ordinal scale scoring in which individual thresholds for each item constitute a distribution by each item. This lead us to hypothesize that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores follow a common mathematical model, which is expressed as the product of the frequency of the total depressive symptom scores and the probability of the cumulative distribution function of each item threshold. To verify this hypothesis, we investigated the boundary curves of the distribution of total depressive symptom scores in a general population. Data collected from 21,040 subjects who had completed the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire as part of a national Japanese survey were analyzed. The CES-D consists of 20 items (16 negative items and four positive items). The boundary curves of adjacent item scores in the distribution of total depressive symptom scores for the 16 negative items were analyzed using log-normal scales and curve fitting. The boundary curves of adjacent item scores for a given symptom approximated a common linear pattern on a log normal scale. Curve fitting showed that an exponential fit had a markedly higher coefficient of determination than either linear or quadratic fits. With negative affect items, the gap between the total score curve and boundary curve continuously increased with increasing total depressive symptom scores on a log-normal scale, whereas the boundary curves of positive affect items, which are not considered manifest variables of the latent trait, did not exhibit such increases in this gap. The results of the present study support the hypothesis that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores commonly follow the predicted mathematical model, which was verified to approximate an exponential mathematical pattern.

Boundary curves of individual items in the distribution of total depressive symptom scores approximate an exponential pattern in a general population

PubMed Central

Kawasaki, Yohei; Akutagawa, Maiko; Yamada, Hiroshi; Furukawa, Toshiaki A.; Ono, Yutaka

2016-01-01

Background Previously, we proposed a model for ordinal scale scoring in which individual thresholds for each item constitute a distribution by each item. This lead us to hypothesize that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores follow a common mathematical model, which is expressed as the product of the frequency of the total depressive symptom scores and the probability of the cumulative distribution function of each item threshold. To verify this hypothesis, we investigated the boundary curves of the distribution of total depressive symptom scores in a general population. Methods Data collected from 21,040 subjects who had completed the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire as part of a national Japanese survey were analyzed. The CES-D consists of 20 items (16 negative items and four positive items). The boundary curves of adjacent item scores in the distribution of total depressive symptom scores for the 16 negative items were analyzed using log-normal scales and curve fitting. Results The boundary curves of adjacent item scores for a given symptom approximated a common linear pattern on a log normal scale. Curve fitting showed that an exponential fit had a markedly higher coefficient of determination than either linear or quadratic fits. With negative affect items, the gap between the total score curve and boundary curve continuously increased with increasing total depressive symptom scores on a log-normal scale, whereas the boundary curves of positive affect items, which are not considered manifest variables of the latent trait, did not exhibit such increases in this gap. Discussion The results of the present study support the hypothesis that the boundary curves of each depressive symptom score in the distribution of total depressive symptom scores commonly follow the predicted mathematical model, which was verified to approximate an exponential mathematical pattern. PMID:27761346

Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients.

PubMed

Khabaz, Mohamad Nidal; Abdelrahman, Amer Shafie; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Al-Maghrabi, Jaudah

2017-10-01

Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P=0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are <40years of age while high proportions of negative staining were observed in older age groups. Histologic type of tissue was also significantly related to cyclin D1 immunohistochemical staining (P-value=0.0001), high staining is more common in normal proliferative and secretory endometrium while serous carcinoma is more prevalent with negative staining. Stage of tumor was significantly associated with cyclin D1 immunohistochemical staining (P-value=0.029), proportion of stage III and IV are higher in negative cyclin D1 immunostaining. Significantly higher proportion of high score cyclin D1 immunostaining is observed in controls while higher proportion of negative cyclin D1 immunostaining is observed among carcinoma cases (P-value=0.0001). No significant associations between cyclin D1 immunohistochemical staining and grade, recurrence and alive status were observed. Significant different survival distributions were observed (P-value=0.011) and poor survival behavior was correlated with negative cyclin D1 immunohistochemical staining. In conclusion, greater frequency of cyclin D1 expression was revealed in normal endometrial tissues in comparison with carcinomas. The distribution pattern of cyclin D1 immunoexpression suggests poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A.

PubMed

Park, Chan Hyuk; Lee, Jung Hwa; Lee, Na Keum; Lee, Yong Chan; Lee, Sang Kil

2016-09-15

Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer.

Pretest Scores Uniquely Predict 1-Year-Delayed Performance in a Simulation-Based Mastery Course for Central Line Insertion.

PubMed

Diederich, Emily; Thomas, Laura; Mahnken, Jonathan; Lineberry, Matthew

2018-06-01

Within simulation-based mastery learning (SBML) courses, there is inconsistent inclusion of learner pretesting, which requires considerable resources and is contrary to popular instructional frameworks. However, it may have several benefits, including its direct benefit as a form of deliberate practice and its facilitation of more learner-specific subsequent deliberate practice. We consider an unexplored potential benefit of pretesting: its ability to predict variable long-term learner performance. Twenty-seven residents completed an SBML course in central line insertion. Residents were tested on simulated central line insertion precourse, immediately postcourse, and after between 64 and 82 weeks. We analyzed pretest scores' prediction of delayed test scores, above and beyond prediction by program year, line insertion experiences in the interim, and immediate posttest scores. Pretest scores related strongly to delayed test scores (r = 0.59, P = 0.01; disattenuated ρ = 0.75). The number of independent central lines inserted also related to year-delayed test scores (r = 0.44, P = 0.02); other predictors did not discernibly relate. In a regression model jointly predicting delayed test scores, pretest was a significant predictor (β = 0.487, P = 0.011); number of independent insertions was not (β = 0.234, P = 0.198). This study suggests that pretests can play a major role in predicting learner variance in learning gains from SBML courses, thus facilitating more targeted refresher training. It also exposes a risk in SBML courses that learners who meet immediate mastery standards may be incorrectly assumed to have equal long-term learning gains.

SCORE should be preferred to Framingham to predict cardiovascular death in French population.

PubMed

Marchant, Ivanny; Boissel, Jean-Pierre; Kassaï, Behrouz; Bejan, Theodora; Massol, Jacques; Vidal, Chrystelle; Amsallem, Emmanuel; Naudin, Florence; Galan, Pilar; Czernichow, Sébastien; Nony, Patrice; Gueyffier, François

2009-10-01

Numerous studies have examined the validity of available scores to predict the absolute cardiovascular risk. We developed a virtual population based on data representative of the French population and compared the performances of the two most popular risk equations to predict cardiovascular death: Framingham and SCORE. A population was built based on official French demographic statistics and summarized data from representative observational studies. The 10-year coronary and cardiovascular death risk and their ratio were computed for each individual by SCORE and Framingham equations. The resulting rates were compared with those derived from national vital statistics. Framingham overestimated French coronary deaths by 2.8 in men and 1.9 in women, and cardiovascular deaths by 1.5 in men and 1.3 in women. SCORE overestimated coronary death by 1.6 in men and 1.7 in women, and underestimated cardiovascular death by 0.94 in men and 0.85 in women. Our results revealed an exaggerated representation of coronary among cardiovascular death predicted by Framingham, with coronary death exceeding cardiovascular death in some individual profiles. Sensitivity analyses gave some insights to explain the internal inconsistency of the Framingham equations. Evidence is that SCORE should be preferred to Framingham to predict cardiovascular death risk in French population. This discrepancy between prediction scores is likely to be observed in other populations. To improve the validation of risk equations, specific guidelines should be issued to harmonize the outcomes definition across epidemiologic studies. Prediction models should be calibrated for risk differences in the space and time dimensions.

Scoring annual earthquake predictions in China

NASA Astrophysics Data System (ADS)

Zhuang, Jiancang; Jiang, Changsheng

2012-02-01

The Annual Consultation Meeting on Earthquake Tendency in China is held by the China Earthquake Administration (CEA) in order to provide one-year earthquake predictions over most China. In these predictions, regions of concern are denoted together with the corresponding magnitude range of the largest earthquake expected during the next year. Evaluating the performance of these earthquake predictions is rather difficult, especially for regions that are of no concern, because they are made on arbitrary regions with flexible magnitude ranges. In the present study, the gambling score is used to evaluate the performance of these earthquake predictions. Based on a reference model, this scoring method rewards successful predictions and penalizes failures according to the risk (probability of being failure) that the predictors have taken. Using the Poisson model, which is spatially inhomogeneous and temporally stationary, with the Gutenberg-Richter law for earthquake magnitudes as the reference model, we evaluate the CEA predictions based on 1) a partial score for evaluating whether issuing the alarmed regions is based on information that differs from the reference model (knowledge of average seismicity level) and 2) a complete score that evaluates whether the overall performance of the prediction is better than the reference model. The predictions made by the Annual Consultation Meetings on Earthquake Tendency from 1990 to 2003 are found to include significant precursory information, but the overall performance is close to that of the reference model.

Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer

PubMed Central

Yamoah, Kosj; Johnson, Michael H.; Choeurng, Voleak; Faisal, Farzana A.; Yousefi, Kasra; Haddad, Zaid; Ross, Ashley E.; Alshalafa, Mohammed; Den, Robert; Lal, Priti; Feldman, Michael; Dicker, Adam P.; Klein, Eric A.; Davicioni, Elai; Rebbeck, Timothy R.; Schaeffer, Edward M.

2015-01-01

Purpose We studied the ethnicity-specific expression of prostate cancer (PC) –associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression. Patients and Methods A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes. Results Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002). Conclusion We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men. PMID:26195723

Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer.

PubMed

Yamoah, Kosj; Johnson, Michael H; Choeurng, Voleak; Faisal, Farzana A; Yousefi, Kasra; Haddad, Zaid; Ross, Ashley E; Alshalafa, Mohammed; Den, Robert; Lal, Priti; Feldman, Michael; Dicker, Adam P; Klein, Eric A; Davicioni, Elai; Rebbeck, Timothy R; Schaeffer, Edward M

2015-09-01

We studied the ethnicity-specific expression of prostate cancer (PC) -associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression. A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes. Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002). We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men. © 2015 by American Society of Clinical Oncology.

Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer.

PubMed

Tóth, Csaba; Sükösd, Farkas; Valicsek, Erzsébet; Herpel, Esther; Schirmacher, Peter; Renner, Marcus; Mader, Christoph; Tiszlavicz, László; Kriegsmann, Jörg

2017-11-01

Liver metastasis in colorectal cancer is common and the primary treatment is chemotherapy. To date, there is no routinely used test in clinical practice to predict the effectiveness of conventional chemotherapy. Therefore, biomarkers with predictive value for conventional chemotherapy would be of considerable benefit in treatment planning. We analysed three proteins [excision repair cross-complementing 1 (ERCC1), ribonucleoside-diphosphate reductase 1 (RRM1) and class III β-tubulin (TUBB3)] in colorectal cancer liver metastasis. We used tissue microarray slides with 101 liver metastasis samples, stained for ERCC1, RRM1 and TUBB3 and established scoring systems (fitted for tissue microarray) for each protein. In statistical analysis, we compared the expression of ERCC1, RRM1 and TUBB3 to mismatch proteins (MLH1, MSH2, MSH6 and PMS2), p53 and to apoptosis repressor protein (ARC). Statistically significant correlations were found between ERCC1, TUBB3 and MLH1, MSH2 and RRM1 and MSH2, MSH6. Noteworthy, our analysis revealed a strong significant correlation between cytoplasmic ARC expression and RRM1, TUBB3 (p=0.000 and p=0.001, respectively), implying an additional role of TUBB3 and RRM1 not only in therapy resistance, but also in the apoptotic machinery. Our data strengthens the importance of ERCC1, TUBB3 and RRM1 in the prediction of chemotherapy effectiveness and suggest new functional connections in DNA repair, microtubule network and apoptotic signaling (i.e. ARC protein). In conclusion, we showed the importance and need of predictive biomarkers in metastasized colorectal cancer and pointed out the relevance not only of single predictive markers but also of their interactions with other known and newly explored relations between different signaling pathways.

Predictive score of sarcopenia occurrence one year after bariatric surgery in severely obese patients.

PubMed

Voican, Cosmin Sebastian; Lebrun, Amandine; Maitre, Sophie; Lainas, Panagiotis; Lamouri, Karima; Njike-Nakseu, Micheline; Gaillard, Martin; Tranchart, Hadrien; Balian, Axel; Dagher, Ibrahim; Perlemuter, Gabriel; Naveau, Sylvie

2018-01-01

Sarcopenic obesity is a risk factor of morbidity and mortality. The aim of this study was to generate a predictive score of sarcopenia occurrence one year after bariatric surgery. We conducted an observational prospective cohort study on a total of 184 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Skeletal muscle cross-sectional area at the third lumbar vertebrae (SMA, cm2) was measured from the routinely performed computed tomography. The skeletal muscle index (SMI) was calculated as follows: SMA/height2 (cm2/m2). Sarcopenia was defined as an SMI < 38.5 cm2/m2 for women and < 52.4 cm2/m2 for men. Measurements were performed at surgery and one year later. Most of the included patients were female (79%), with a mean age of 42±0.9 years and body mass index of 43.2±0.5 kg/m2. Fifteen patients (8%) had sarcopenia before surgery and 59 (32%) at the one-year follow-up. Male gender (p<0.0001), SMA before surgery (p<0.0001), and SMI before surgery (p<0.0001) significantly correlated with the occurrence of sarcopenia one year after surgery by multivariate analysis. Two predictive sarcopenia occurrence scores were constructed using SMA and gender (SS1 score) or SMI and gender (SS2 score). The area under receiver operating characteristic (AUROC) curve of the SS2 score was significantly greater than that of the SS1 score for the diagnosis of postoperative sarcopenia occurrence (0.95±0.02 versus 0.90±0.02; p<0.01). A cut-off value for the SS2 score of 0.53 had a sensitivity of 90%, a specificity of 91%, a positive predictive value of 83%, and a negative predictive value of 95%. In the group of patients without baseline sarcopenia, the SS2 score had still an excellent AUROC of 0.92±0.02. A cut-off of 0.55 predicted development of sarcopenia one year after sleeve gastrectomy in these patients with a sensitivity of 87%, a specificity of 88%, and negative predictive value of 95%. The SS2 score has excellent predictive value for the occurrence of sarcopenia one year after sleeve gastrectomy. This score can be used to target early intensification of nutritional and dietetic follow-up to the predicted high-risk population.

Alberta Stroke Program Early CT Score-Time Score Predicts Outcome after Endovascular Therapy in Patients with Acute Ischemic Stroke: A Retrospective Single-Center Study.

PubMed

Todo, Kenichi; Sakai, Nobuyuki; Kono, Tomoyuki; Hoshi, Taku; Imamura, Hirotoshi; Adachi, Hidemitsu; Yamagami, Hiroshi; Kohara, Nobuo

2018-04-01

Clinical outcomes after successful endovascular therapy in patients with acute ischemic stroke are associated with several factors including onset-to-reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS) score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time score, calculated as follows: [NIHSS score] × [onset-to-treatment time (h)] or [NIHSS score] × [ORT (h)], has been reported to predict clinical outcomes after intravenous recombinant tissue plasminogen activator therapy and endovascular therapy for acute stroke. The objective of the current study was to assess whether the combination of the ASPECTS and the ORT can predict the outcomes after endovascular therapy. The charts of 117 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy were retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as follows: [11 - ASPECTS] × [ORT (h)]. Rates of good outcome for patients with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and 33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that the ASPECTS-time score (per category increase) was an independent predictor for better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P < .05). A lower ASPECTS-time score may predict better clinical outcomes after endovascular treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

PCTFPeval: a web tool for benchmarking newly developed algorithms for predicting cooperative transcription factor pairs in yeast.

PubMed

Lai, Fu-Jou; Chang, Hong-Tsun; Wu, Wei-Sheng

2015-01-01

Computational identification of cooperative transcription factor (TF) pairs helps understand the combinatorial regulation of gene expression in eukaryotic cells. Many advanced algorithms have been proposed to predict cooperative TF pairs in yeast. However, it is still difficult to conduct a comprehensive and objective performance comparison of different algorithms because of lacking sufficient performance indices and adequate overall performance scores. To solve this problem, in our previous study (published in BMC Systems Biology 2014), we adopted/proposed eight performance indices and designed two overall performance scores to compare the performance of 14 existing algorithms for predicting cooperative TF pairs in yeast. Most importantly, our performance comparison framework can be applied to comprehensively and objectively evaluate the performance of a newly developed algorithm. However, to use our framework, researchers have to put a lot of effort to construct it first. To save researchers time and effort, here we develop a web tool to implement our performance comparison framework, featuring fast data processing, a comprehensive performance comparison and an easy-to-use web interface. The developed tool is called PCTFPeval (Predicted Cooperative TF Pair evaluator), written in PHP and Python programming languages. The friendly web interface allows users to input a list of predicted cooperative TF pairs from their algorithm and select (i) the compared algorithms among the 15 existing algorithms, (ii) the performance indices among the eight existing indices, and (iii) the overall performance scores from two possible choices. The comprehensive performance comparison results are then generated in tens of seconds and shown as both bar charts and tables. The original comparison results of each compared algorithm and each selected performance index can be downloaded as text files for further analyses. Allowing users to select eight existing performance indices and 15 existing algorithms for comparison, our web tool benefits researchers who are eager to comprehensively and objectively evaluate the performance of their newly developed algorithm. Thus, our tool greatly expedites the progress in the research of computational identification of cooperative TF pairs.

PCTFPeval: a web tool for benchmarking newly developed algorithms for predicting cooperative transcription factor pairs in yeast

PubMed Central

2015-01-01

Background Computational identification of cooperative transcription factor (TF) pairs helps understand the combinatorial regulation of gene expression in eukaryotic cells. Many advanced algorithms have been proposed to predict cooperative TF pairs in yeast. However, it is still difficult to conduct a comprehensive and objective performance comparison of different algorithms because of lacking sufficient performance indices and adequate overall performance scores. To solve this problem, in our previous study (published in BMC Systems Biology 2014), we adopted/proposed eight performance indices and designed two overall performance scores to compare the performance of 14 existing algorithms for predicting cooperative TF pairs in yeast. Most importantly, our performance comparison framework can be applied to comprehensively and objectively evaluate the performance of a newly developed algorithm. However, to use our framework, researchers have to put a lot of effort to construct it first. To save researchers time and effort, here we develop a web tool to implement our performance comparison framework, featuring fast data processing, a comprehensive performance comparison and an easy-to-use web interface. Results The developed tool is called PCTFPeval (Predicted Cooperative TF Pair evaluator), written in PHP and Python programming languages. The friendly web interface allows users to input a list of predicted cooperative TF pairs from their algorithm and select (i) the compared algorithms among the 15 existing algorithms, (ii) the performance indices among the eight existing indices, and (iii) the overall performance scores from two possible choices. The comprehensive performance comparison results are then generated in tens of seconds and shown as both bar charts and tables. The original comparison results of each compared algorithm and each selected performance index can be downloaded as text files for further analyses. Conclusions Allowing users to select eight existing performance indices and 15 existing algorithms for comparison, our web tool benefits researchers who are eager to comprehensively and objectively evaluate the performance of their newly developed algorithm. Thus, our tool greatly expedites the progress in the research of computational identification of cooperative TF pairs. PMID:26677932

Bishop score and ultrasound assessment of the cervix for prediction of time to onset of labor and time to delivery in prolonged pregnancy.

PubMed

Strobel, E; Sladkevicius, P; Rovas, L; De Smet, F; Karlsson, E Dejin; Valentin, L

2006-09-01

To determine the ability of Bishop score and sonographic cervical length to predict time to spontaneous onset of labor and time to delivery in prolonged pregnancy. Ninety-seven women underwent transvaginal ultrasound examination and palpation of the cervix at 291-296 days' gestation according to ultrasound fetometry at 12-20 weeks' gestation. Sonographic cervical length and Bishop score were recorded. Multivariate logistic regression analysis was used to determine which variables were independent predictors of the onset of labor/delivery < or = 24 h, < or = 48 h, and < or = 96 h. Receiver-operating characteristics (ROC) curves were drawn to assess diagnostic performance. In nulliparous women (n = 45), both Bishop score and sonographic cervical length predicted the onset of labor/delivery < or = 24 h and < or = 48 h (area under ROC curve for the onset of labor < or = 24 h 0.79 vs. 0.80, P = 0.94; for delivery < or = 24 h 0.81 vs. 0.85, P = 0.64; for the onset of labor < or = 48 h 0.73 vs. 0.74, P = 0.90; for delivery < or = 48 h 0.77 vs. 0.71, P = 0.50). Only Bishop score discriminated between nulliparous women who went into labor/delivered < or = 96 h or > 96 h. A logistic regression model including Bishop score and cervical length was superior to Bishop score alone in predicting delivery < or = 24 h (area under ROC curve 0.93 vs. 0.81, P = 0.03) and superior to Bishop score alone and cervical length alone in predicting the onset of labor < or = 24 h (area under ROC curve 0.90 vs. 0.79, P = 0.06; and 0.90 vs. 0.80, P = 0.06). In parous women (n = 52), Bishop score and sonographic cervical length predicted the onset of labor/delivery < or = 24 h (area under ROC curve for the onset of labor 0.75 vs. 0.69, P = 0.49; for delivery 0.74 vs. 0.70, P = 0.62), but only Bishop score discriminated between women who went into labor/delivered < or = 48 h and > 48 h. Three parous women had not gone into labor and six had not given birth at 96 h. In parous women logistic regression models including both Bishop score and cervical length did not substantially improve prediction of the time to onset of labor/delivery. In prolonged pregnancy Bishop score and sonographic cervical length have a similar ability to predict the time to the onset of labor and delivery. In nulliparous women the use of logistic regression models including Bishop score and cervical length is likely to offer better prediction of the onset of labor/delivery < or = 24 h than the use of the Bishop score alone. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Maternal Depression and Expressive Communication in One-Year-Old Infants

PubMed Central

Kaplan, Peter S.; Danko, Christina M.; Everhart, Kevin D.; Diaz, Andres; Asherin, Ryan; Vogeli, JoAnn; Fekri, Shiva

2014-01-01

To separate effects of maternal depression on infant cognitive versus language development, 1-year-olds were assessed using the revised Bayley Scales of Infant and Toddler Development (BSID-III). Percentile scores on the Bayley Expressive Communication (EC) subscale were significantly negatively correlated with maternal self-report scores on the Beck Depression Inventory (BDI-II). However, mothers’ BDI-II scores did not correlate with infant percentile scores on the general cognitive (COG) or receptive communication (RC) subscales. Boys had significantly lower percentile scores than girls on the RC and EC scales, but did not differ on the Cog scale. Gender and maternal depression did not significantly interact on any of the scales. These findings suggest problems with expressive communication precede, and may at least partially account for, apparent deficits in general cognitive development. PMID:24953222

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

PubMed

Thandassery, Ragesh B; Al Kaabi, Saad; Soofi, Madiha E; Mohiuddin, Syed A; John, Anil K; Al Mohannadi, Muneera; Al Ejji, Khalid; Yakoob, Rafie; Derbala, Moutaz F; Wani, Hamidullah; Sharma, Manik; Al Dweik, Nazeeh; Butt, Mohammed T; Kamel, Yasser M; Sultan, Khaleel; Pasic, Fuad; Singh, Rajvir

2016-07-01

Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

PubMed

Mucci, A; Galderisi, S; Green, M F; Nuechterlein, K; Rucci, P; Gibertoni, D; Rossi, A; Rocca, P; Bertolino, A; Bucci, P; Hellemann, G; Spisto, M; Palumbo, D; Aguglia, E; Amodeo, G; Amore, M; Bellomo, A; Brugnoli, R; Carpiniello, B; Dell'Osso, L; Di Fabio, F; di Giannantonio, M; Di Lorenzo, G; Marchesi, C; Monteleone, P; Montemagni, C; Oldani, L; Romano, R; Roncone, R; Stratta, P; Tenconi, E; Vita, A; Zeppegno, P; Maj, M

2018-06-01

The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Dietary diversity scores can be improved through the use of portion requirements: an analysis in young Filipino children.

PubMed

Daniels, M C; Adair, L S; Popkin, B M; Truong, Y K

2009-02-01

Early childhood malnutrition is a pressing international concern which dietary diversity scores (summary scores of food groups in the diet) may be helpful in addressing. We explored three current research needs surrounding diversity scores: the impact of portion size on score function, the relationship of scores to nutrient adequacy and density and the ability of scores to function as screening tools. 1810 children, age 24 months. Cross sectional study of a birth cohort. We evaluated two nine food group dietary diversity scores based on 0 and 10 g minimum food group requirements for their relationship to nutrient adequacy and nutrient density. Both scores were significantly correlated with nutrient adequacy and density and predicted statistically significant increases (P<0.05) in the probability of adequacy for all nutrients. However, correlations and predicted increases were somewhat larger for the 10 g score. We also considered the sensitivity and specificity of each score for detecting low and high nutrient adequacy in the population. The 10 g cutoff improved score ability to predict low nutrient adequacy, and reduced the misclassification of subjects for all comparisons. This research suggests that the score without portion requirements reflects dietary adequacy, but when feasible, further refinement of diversity scores is desirable through the application of minimum portion requirements.

Psychological Assessment of Adolescents and Adults with Autism.

ERIC Educational Resources Information Center

Perez, Juan; del Sol Fortea Sevilla, Maria

1993-01-01

This study compared scores of 17 children with autism and mental retardation on the Psychoeducational Profile with scores on the Adolescent and Adult Psychoeducational Profile 5 years later. Eye-hand coordination predicted scores in vocational skills, independent functioning, and vocational behavior; imitation predicted interpersonal behavior;…

A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival.

PubMed

Botta, C; Di Martino, M T; Ciliberto, D; Cucè, M; Correale, P; Rossi, M; Tagliaferri, P; Tassone, P

2016-12-16

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.

The prognostic value of a seven-microRNA classifier as a novel biomarker for the prediction and detection of recurrence in glioma patients.

PubMed

Chen, Wanghao; Yu, Qiang; Chen, Bo; Lu, Xingyu; Li, Qiaoyu

2016-08-16

Glioma is often diagnosed at a later stage, and the high risk of recurrence remains a major challenge. We hypothesized that the microRNA expression profile may serve as a biomarker for the prognosis and prediction of glioblastoma recurrence. We defined microRNAs that were associated with good and poor prognosis in 300 specimens of glioblastoma from the Cancer Genome Atlas. By analyzing microarray gene expression data and clinical information from three random groups, we identified 7 microRNAs that have prognostic and prognostic accuracy: microRNA-124a, microRNA-129, microRNA-139, microRNA-15b, microRNA-21, microRNA-218 and microRNA-7. The differential expression of these miRNAs was verified using an independent set of glioma samples from the Affiliated People's Hospital of Jiangsu University. We used the log-rank test and the Kaplan-Meier method to estimate correlations between the miRNA signature and disease-free survival/overall survival. Using the LASSO model, we observed a uniform significant difference in disease-free survival and overall survival between patients with high-risk and low-risk miRNA signature scores. Furthermore, the prognostic capability of the seven-miRNA signature was demonstrated by receiver operator characteristic curve analysis. A Circos plot was generated to examine the network of genes and pathways predicted to be targeted by the seven-miRNA signature. The seven-miRNA-based classifier should be useful in the stratification and individualized management of patients with glioma.

Language Impairment From 4 to 12 Years: Prediction and Etiology

PubMed Central

Hayiou-Thomas, Marianna E.; Dale, Philip S.; Plomin, Robert

2014-01-01

Purpose The authors of this article examined the etiology of developmental language impairment (LI) at 4 and 12 years of age, as well as the relationship between the 2. Method Phenotypic and quantitative genetic analyses using longitudinal data from the Twins Early Development Study (Oliver & Plomin, 2007) were conducted. A total of 2,923 pairs of twins (1,075 monozygotic [MZ]; 975 dizygotic same sex [DZss]; and 873 dizygotic opposite sex [DZos]) provided data at 4 and 12 years. At 4 years, (a) psychometric LI was defined on the basis of a low parent-reported expressive vocabulary score (−1.25 SDs; 226 MZ and 115 DZss probands for genetic analysis); and (b) parent referral was defined as having seen a medical professional or speech-language pathologist following parental concern (112 MZ and 104 DZss probands). The 12-year language measure was a composite of 4 web-administered receptive language tests. Results (a) Psychometric LI at 4 years is more predictive than parent referral of poor language performance at age 12 years, and (b) parent referral is substantially and significantly more heritable than psychometric LI. Conclusions Parents’ concern about their child’s language development seems to be the marker of a more heritable disorder than poor expressive language skills alone. However, the language difficulties that arouse parental concern in preschool children, although more heritable, are not predictive of language difficulties in early adolescence. Rather, poor expressive language skills at age 4 years, psychometrically defined, are a better predictor than parent referral of continuing language difficulties at age 12 years. PMID:24167234

The STarT Back Screening Tool and Individual Psychological Measures: Evaluation of Prognostic Capabilities for Low Back Pain Clinical Outcomes in Outpatient Physical Therapy Settings

PubMed Central

Bishop, Mark D.; Fritz, Julie M.; Robinson, Michael E.; Asal, Nabih R.; Nisenzon, Anne N.

2013-01-01

Background Psychologically informed practice emphasizes routine identification of modifiable psychological risk factors being highlighted. Objective The purpose of this study was to test the predictive validity of the STarT Back Screening Tool (SBT) in comparison with single-construct psychological measures for 6-month clinical outcomes. Design This was an observational, prospective cohort study. Methods Patients (n=146) receiving physical therapy for low back pain were administered the SBT and a battery of psychological measures (Fear-Avoidance Beliefs Questionnaire physical activity scale and work scale [FABQ-PA and FABQ-W, respectively], Pain Catastrophizing Scale [PCS], 11-item version of the Tampa Scale of Kinesiophobia [TSK-11], and 9-item Patient Health Questionnaire [PHQ-9]) at initial evaluation and 4 weeks later. Treatment was at the physical therapist's discretion. Clinical outcomes consisted of pain intensity and self-reported disability. Prediction of 6-month clinical outcomes was assessed for intake SBT and psychological measure scores using multiple regression models while controlling for other prognostic variables. In addition, the predictive capabilities of intake to 4-week changes in SBT and psychological measure scores for 6-month clinical outcomes were assessed. Results Intake pain intensity scores (β=.39 to .45) and disability scores (β=.47 to .60) were the strongest predictors in all final regression models, explaining 22% and 24% and 43% and 48% of the variance for the respective clinical outcome at 6 months. Neither SBT nor psychological measure scores improved prediction of 6-month pain intensity. The SBT overall scores (β=.22) and SBT psychosocial scores (β=.25) added to the prediction of disability at 6 months. Four-week changes in TSK-11 scores (β=−.18) were predictive of pain intensity at 6 months. Four-week changes in FABQ-PA scores (β=−.21), TSK-11 scores (β=−.20) and SBT overall scores (β=−.18) were predictive of disability at 6 months. Limitations Physical therapy treatment was not standardized or accounted for in the analysis. Conclusions Prediction of clinical outcomes by psychology-based measures was dependent upon the clinical outcome domain of interest. Similar to studies from the primary care setting, initial screening with the SBT provided additional prognostic information for 6-month disability and changes in SBT overall scores may provide important clinical decision-making information for treatment monitoring. PMID:23125279

Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer.

PubMed

Wako, K; Kawasaki, T; Yamana, K; Suzuki, K; Jiang, S; Umezu, H; Nishiyama, T; Takahashi, K; Hamakubo, T; Kodama, T; Naito, M

2008-04-01

The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined. PCa specimens from 44 cases of stage II, 10 cases of stage III, four cases of stage IV and two recurrent cases were semi-quantitatively studied with immunohistochemistry for AR and androgen-converting enzymes. The expression scores for AR, 5alpha-reductase type 1 (SRD5A1), 5alpha-reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion of stage IV or recurrent cancer (n = 6) were 284.2 (30.1), 300 (0.0), 279.2 (51) and 254.2 (74.9), respectively; these scores were significantly higher than the respective scores of 121.8 (82.1), 135.1 (59.7), 167.0 (66.4) and 150.5 (62.8) for stage II and III cancer (n = 54) (p<0.001, p<0.001, p = 0.002 and p = 0.018, respectively). The expression scores for AR and SRD5A1 in stage II and III cancer with Gleason score 7 (n = 19) were 128.7 (72.3) and 150.5 (52.9); these were significantly higher than the scores of 78.8 (67.2) and 100.0 (39.6), respectively, for cancers with a Gleason score of < or =6 (n = 20) (p = 0.032 and p = 0.002, respectively). The expression scores for AR, SRD5A1 and AKR1C3 in stage II and III cancer with primary Gleason pattern > or =4 (n = 21) were 158.1 (84.3), 158.3 (61.1) and 173.8 (64.8); these were significantly higher than the scores of 98.6 (72.8), 120.3 (54.7) and 135.6 (57.6), respectively, for cancers with primary Gleason pattern < or =3 (n = 33) (p = 0.011, p = 0.026 and p = 0.034, respectively). Within Gleason score 9 cancer, the expression scores for AR and SRD5A1 in the primary lesion of stage IV (n = 3) were 276.7 (5.8) and 283.3 (28.9); these scores were significantly higher than the scores of 182.1 (86.0) and 140.0 (56.6), respectively, for stage II and III cancer (n = 7) (p = 0.027 and p = 0.001, respectively). Both AR and androgen-converting enzymes were upregulated in high-grade or advanced PCa.

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

PubMed

Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

2014-07-30

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Use of a pretest strategy for physical therapist assistant programs to predict success rate on the national physical therapy exam.

PubMed

Sloas, Stacey B; Keith, Becky; Whitehead, Malcolm T

2013-01-01

This study investigated a pretest strategy that identified physical therapist assistant (PTA) students who were at risk of failure on the National Physical Therapy Examination (NPTE). Program assessment data from five cohorts of PTA students (2005-2009) were used to develop a stepwise multiple regression formula that predicted first-time NPTE licensure scores. Data used included the Nelson-Denny Reading Test, grades from eight core courses, grade point average upon admission to the program, and scores from three mock NPTE exams given during the program. Pearson correlation coefficients were calculated between each of the 15 variables and NPTE scores. Stepwise multiple regression analysis was performed using data collected at the ends of the first, second, and third (final) semesters of the program. Data from the class of 2010 were then used to validate the formula. The end-of-program formula accounted for the greatest variance (57%) in predicted scores. Those students scoring below a predicted scaled score of 620 were identified to be at risk of failure of the licensure exam. These students were counseled, and a remedial plan was developed based on regression predictions prior to them sitting for the licensure exam.

RBANS memory percentage retention: No evidence of incremental validity beyond RBANS scores for diagnostic classification of mild cognitive impairment and dementia and for prediction of daily function.

PubMed

Jodouin, Kara A; O'Connell, Megan E; Morgan, Debra G

2017-01-01

RBANS percentage retention scores may be useful for diagnosis, but their incremental validity is unclear. Percentage retention versus RBANS immediate and delayed memory subtests and delayed index scores were compared for diagnostic classification and for prediction of function. Data from 173 memory clinic patients with an interdisciplinary diagnosis (no cognitive impairment, amnestic mild cognitive impairment [aMCI], and dementia due to Alzheimer's disease [AD]) and complete RBANS data were analyzed. Across diagnostic contrasts, list percentage retention classification accuracy was similar to List Learning delayed recall, but below the Delayed Memory Index (DMI). Similarly, for classifying no cognitive impairment versus aMCI or dementia due to AD, story percentage retention was similar to Story Memory subtests and below the DMI. For classifying aMCI versus AD; however, Story Memory exceeded the DMI, but was similar to Story Memory subtest scores. Similarly, for prediction of function percentage retention measures did not predict variance beyond that predicted by the RBANS subtest or index scores. In sum, there is no evidence that calculation of percentage retention for RBANS adds clinical utility beyond those provided by the standard RBANS scores.

Noninvasive scoring system for significant inflammation related to chronic hepatitis B

NASA Astrophysics Data System (ADS)

Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

2017-03-01

Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (-) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (-) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

Estimating severity of burn in children: Pediatric Risk of Mortality (PRISM) score versus Abbreviated Burn Severity Index (ABSI).

PubMed

Berndtson, Allison E; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

2013-09-01

The purpose of our study is to validate the Pediatric Risk of Mortality (PRISM) score and compare the accuracy of PRISM predicted outcomes to the Abbreviated Burn Severity Index (ABSI). We hypothesized that the PRISM score is more accurate in predicting mortality and hospital length of stay than the ABSI in children with severe burns. All children <18 years of age admitted to a regional pediatric burn center between January 1, 2008 and July 1, 2010 were reviewed. Those with a Total Body Surface Area (TBSA) burn ≥20% who were admitted within 7 days of injury were selected for our study. Measured parameters included: demographics, burn characteristics, PRISM and ABSI scores at admission, and outcomes (mortality, hospital length of stay (LOS), ventilator days and cause of death). A total of 83 patients met criteria and had complete data sets. The mean age (±SEM) was 8.0±0.6 years, mean % TBSA burn 49.9±2.1%, 62.7% were male, and 45.8% had inhalation injury. Hospital LOS was 74.4±7.9 days, with 31.5±4.9 ventilator days. Mean PRISM score ranged from 14.2 to 16.0, with ABSI scores 7.9 to 8.5. Actual overall mortality was 18.1% compared to a PRISM predicted mortality of 19.8±2.5% (p<0.001, r=0.570). ABSI predicted mortality varied from 10 to 20% for a score of 7.9 to 30-50% for a score of 8.5. Logistic regression showed that both PRISM (p<0.001) and ABSI (p<0.001) mortality predictions accurately estimated actual mortality, which remained true in a combined model. ABSI was predictive of hospital LOS (p<0.001) and ventilator days (p<0.001) while PRISM was not (p=0.326 and p=0.863). Both PRISM and ABSI scores are predictive of mortality in severely burned children. Only ABSI correlates with hospital length of stay and ventilator days, and thus may also be more useful in predicting ICU resource utilization. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

The impact of undergraduate occupational therapy students' interpersonal skills on their practice education performance: A pilot study.

PubMed

Yu, Mong-Lin; Brown, Ted; White, Carolynne; Marston, Celia; Thyer, Laura

2018-04-01

Interpersonal skills such as active listening, verbal communication and body language are essential competencies for occupational therapists, and students are expected to demonstrate these skills when completing practice placements. To investigate whether interpersonal skills are predictive of occupational therapy students' practice performance. A cross-sectional study was conducted involving third and fourth year occupational therapy undergraduate students (n = 70). Students' interpersonal skills were measured using the Interpersonal Communication Competence Scale (ICCS), Listening Styles Profile (LSP-R) and Active-Empathic Listening Scale (AELS). Students' practice performances at the mid-way and final points of their placements were measured using the Student Practice Evaluation Form-Revised (SPEF-R). The relationships between students' interpersonal skills and practice performance were examined using univariate and multi-variate regressions. Higher ICCS Interaction Management subscale scores predicted better SPEF-R Self-Management Skills at the mid-way point through practice placements (β = 1.93, SE = 0.76), and better Professional Behaviours (β = 1.28, SE = 0.64) and better Service Evaluation Skills (β = 2.84, SE = 0.95) at the final SPEF-R completion point. Higher ICCS Empathy subscale scores predicted lower SPEF-R Documentation scores at the mid-way point (β = -0.81, SE = 0.38), while higher ICCS Supportiveness subscale scores predicted lower mid-way SPEF-R Service Provision scores (β = -2.84, SE = 1.77). No ICCS subscale scores were predictive of the SPEF-R communication, co-worker communication and information gathering subscale scores. As well, LSP-R and AELS subscale scores were not predictive of the SPEF-R subscale scores. While predictive relationships were not found between occupational therapy students' communication, co-worker communication and information gathering skills, this preliminary evidence indicates that students' interpersonal skills (including interaction management and empathetic supportiveness) were predictive of some notable SPEF-R competencies (including Professional Behaviours, Self-Management, Documentation, Service Provision and Service Evaluation). Therefore, students' exposure to professional interpersonal skills should be incorporated into the curriculum of academic education programs with the aim of better preparing them for practice education. © 2018 Occupational Therapy Australia.

Vietnamese children and language-based processing tasks.

PubMed

Hwa-Froelich, Deborah A; Matsuo, Hisako

2005-07-01

Vietnamese children's performance on language-based processing tasks of fast-mapping (FM) word-learning and dynamic assessment (DA) word- and rule-learning tasks were investigated. Twenty-one first- and second-generation Vietnamese preschool children participated in this study. All children were enrolled in 2 Head Start programs in a large city in the Midwest. All children had passed a developmental assessment and routine speech, language, and hearing screenings. All participants were taught 4 invented monosyllabic words in an FM word task, an invented monosyllabic suffix rule (-po) meaning "a part of" in a DA rule task, and 4 invented bisyllabic words in a DA word task. Potential relationships among task performances were investigated. Receptive task performances, expressive task performances, and task totals were added to create receptive total, expressive total, and accumulated performance total (APT) scores. Relationships among receptive total, expressive total, and APT scores were also investigated. Significant correlations were found between FM word, DA rule, and the receptive total. The expressive total correlated with all task total scores, APT, age, and modifiability scores. Modifiability scores correlated with the two DA tasks, expressive total, and the APT. Findings indicate that FM word and the expressive total were positively correlated with most of the other tasks, composite totals, and age. Performance on language-based processing tasks may provide valuable information for separating typically developing Vietnamese preschool children from their peers with language disorders. Practitioners should consider linguistic characteristics of target stimuli. Comparisons should include task, receptive, expressive, and APT.

A method for predicting target drug efficiency in cancer based on the analysis of signaling pathway activation.

PubMed

Artemov, Artem; Aliper, Alexander; Korzinkin, Michael; Lezhnina, Ksenia; Jellen, Leslie; Zhukov, Nikolay; Roumiantsev, Sergey; Gaifullin, Nurshat; Zhavoronkov, Alex; Borisov, Nicolas; Buzdin, Anton

2015-10-06

A new generation of anticancer therapeutics called target drugs has quickly developed in the 21st century. These drugs are tailored to inhibit cancer cell growth, proliferation, and viability by specific interactions with one or a few target proteins. However, despite formally known molecular targets for every "target" drug, patient response to treatment remains largely individual and unpredictable. Choosing the most effective personalized treatment remains a major challenge in oncology and is still largely trial and error. Here we present a novel approach for predicting target drug efficacy based on the gene expression signature of the individual tumor sample(s). The enclosed bioinformatic algorithm detects activation of intracellular regulatory pathways in the tumor in comparison to the corresponding normal tissues. According to the nature of the molecular targets of a drug, it predicts whether the drug can prevent cancer growth and survival in each individual case by blocking the abnormally activated tumor-promoting pathways or by reinforcing internal tumor suppressor cascades. To validate the method, we compared the distribution of predicted drug efficacy scores for five drugs (Sorafenib, Bevacizumab, Cetuximab, Sorafenib, Imatinib, Sunitinib) and seven cancer types (Clear Cell Renal Cell Carcinoma, Colon cancer, Lung adenocarcinoma, non-Hodgkin Lymphoma, Thyroid cancer and Sarcoma) with the available clinical trials data for the respective cancer types and drugs. The percent of responders to a drug treatment correlated significantly (Pearson's correlation 0.77 p = 0.023) with the percent of tumors showing high drug scores calculated with the current algorithm.