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Sample records for profiling predicts clinical

  1. Clinical, nociceptive and psychological profiling to predict acute pain after total knee arthroplasty

    DEFF Research Database (Denmark)

    Luna, I E; Kehlet, H; Petersen, M A

    2017-01-01

    outcome. Predictive variables collected prior to surgery included demographics, nociceptive testing (pressure pain threshold (PPT), cold pressor tolerance, electrical pain threshold and tolerance) and psychological profile (pain catastrophizing scale (PCS) and hospital anxiety and depression scale...... catastrophizing are predictive of moderate severe post-TKA pain. If validated in a larger population, the clinically applicable tests should be considered in future interventions aiming to minimize post-operative pain in high-risk patients....

  2. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  3. Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models.

    Science.gov (United States)

    Yousefi, Safoora; Amrollahi, Fatemeh; Amgad, Mohamed; Dong, Chengliang; Lewis, Joshua E; Song, Congzheng; Gutman, David A; Halani, Sameer H; Velazquez Vega, Jose Enrique; Brat, Daniel J; Cooper, Lee A D

    2017-09-15

    Translating the vast data generated by genomic platforms into accurate predictions of clinical outcomes is a fundamental challenge in genomic medicine. Many prediction methods face limitations in learning from the high-dimensional profiles generated by these platforms, and rely on experts to hand-select a small number of features for training prediction models. In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem of predicting cancer outcomes. We perform an extensive comparison of Bayesian optimized deep survival models and other state of the art machine learning methods for survival analysis, and describe a framework for interpreting deep survival models using a risk backpropagation technique. Finally, we illustrate that deep survival models can successfully transfer information across diseases to improve prognostic accuracy. We provide an open-source software implementation of this framework called SurvivalNet that enables automatic training, evaluation and interpretation of deep survival models.

  4. Prediction of Clinical Outcome Using Gene Expression Profiling and Artificial Neural Networks for Patients with Neuroblastoma

    Science.gov (United States)

    Wei, Jun S.; Greer, Braden T.; Westermann, Frank; Steinberg, Seth M.; Son, Chang-Gue; Chen, Qing-Rong; Whiteford, Craig C.; Bilke, Sven; Krasnoselsky, Alexei L.; Cenacchi, Nicola; Catchpoole, Daniel; Berthold, Frank; Schwab, Manfred; Khan, Javed

    2005-01-01

    Currently, patients with neuroblastoma are classified into risk groups (e.g., according to the Children’s Oncology Group risk-stratification) to guide physicians in the choice of the most appropriate therapy. Despite this careful stratification, the survival rate for patients with high-risk neuroblastoma remains artificial neural networks to develop an accurate predictor of survival for each individual patient with neuroblastoma. Using principal component analysis we found that neuroblastoma tumors exhibited inherent prognostic specific gene expression profiles. Subsequent artificial neural network-based prognosis prediction using expression levels of all 37,920 good-quality clones achieved 88% accuracy. Moreover, using an artificial neural network-based gene minimization strategy in a separate analysis we identified 19 genes, including 2 prognostic markers reported previously, MYCN and CD44, which correctly predicted outcome for 98% of these patients. In addition, these 19 predictor genes were able to additionally partition Children’s Oncology Group-stratified high-risk patients into two subgroups according to their survival status (P = 0.0005). Our findings provide evidence of a gene expression signature that can predict prognosis independent of currently known risk factors and could assist physicians in the individual management of patients with high-risk neuroblastoma. PMID:15466177

  5. Predicting clinical concussion measures at baseline based on motivation and academic profile.

    Science.gov (United States)

    Trinidad, Katrina J; Schmidt, Julianne D; Register-Mihalik, Johna K; Groff, Diane; Goto, Shiho; Guskiewicz, Kevin M

    2013-11-01

    The purpose of this study was to predict baseline neurocognitive and postural control performance using a measure of motivation, high school grade point average (hsGPA), and Scholastic Aptitude Test (SAT) score. Cross-sectional. Clinical research center. Eighty-eight National Collegiate Athletic Association Division I incoming student-athletes (freshman and transfers). Participants completed baseline clinical concussion measures, including a neurocognitive test battery (CNS Vital Signs), a balance assessment [Sensory Organization Test (SOT)], and motivation testing (Rey Dot Counting). Participants granted permission to access hsGPA and SAT total score. Standard scores for each CNS Vital Signs domain and SOT composite score. Baseline motivation, hsGPA, and SAT explained a small percentage of the variance of complex attention (11%), processing speed (12%), and composite SOT score (20%). Motivation, hsGPA, and total SAT score do not explain a significant amount of the variance in neurocognitive and postural control measures but may still be valuable to consider when interpreting neurocognitive and postural control measures.

  6. The clinical utility of lipid profile and positive troponin in predicting future cardiac events

    OpenAIRE

    Arun Kumar; Brijesh Sathian

    2012-01-01

    Objective: To study the usefulness of traditional lipid profile levels in screening subjects who had developed chest pain due to cardiac event as indicated by a positive troponin I (TnI) test. Methods: In this retrospective study data of the 740 patients presented to the emergency department with symptoms of cardiac ischemia that underwent both troponin and lipid profiles tests were compared with the lipid profiles of 411 normal healthy subjects (controls). The troponin was det...

  7. Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models

    National Research Council Canada - National Science Library

    Safoora Yousefi; Fatemeh Amrollahi; Mohamed Amgad; Chengliang Dong; Joshua E Lewis; Congzheng Song; David A Gutman; Sameer H Halani; Jose Enrique Velazquez Vega; Daniel J Brat; Lee A D Cooper

    2017-01-01

    .... In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem...

  8. Maximum predictive power of the microarray-based models for clinical outcomes is limited by correlation between endpoint and gene expression profile.

    Science.gov (United States)

    Zhao, Chen; Shi, Leming; Tong, Weida; Shaughnessy, John D; Oberthuer, André; Pusztai, Lajos; Deng, Youping; Symmans, W Fraser; Shi, Tieliu

    2011-12-23

    Microarray data have been used for gene signature selection to predict clinical outcomes. Many studies have attempted to identify factors that affect models' performance with only little success. Fine-tuning of model parameters and optimizing each step of the modeling process often results in over-fitting problems without improving performance. We propose a quantitative measurement, termed consistency degree, to detect the correlation between disease endpoint and gene expression profile. Different endpoints were shown to have different consistency degrees to gene expression profiles. The validity of this measurement to estimate the consistency was tested with significance at a p-value less than 2.2e-16 for all of the studied endpoints. According to the consistency degree score, overall survival milestone outcome of multiple myeloma was proposed to extend from 730 days to 1561 days, which is more consistent with gene expression profile. For various clinical endpoints, the maximum predictive powers of different microarray-based models are limited by the correlation between endpoint and gene expression profile of disease samples as indicated by the consistency degree score. In addition, previous defined clinical outcomes can also be reassessed and refined more coherent according to related disease gene expression profile. Our findings point to an entirely new direction for assessing the microarray-based predictive models and provide important information to gene signature based clinical applications.

  9. HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors.

    Science.gov (United States)

    de Jong, Monique C; Pramana, Jimmy; Knegjens, Joost L; Balm, Alfons J M; van den Brekel, Michiel W M; Hauptmann, Michael; Begg, Adrian C; Rasch, Coen R N

    2010-06-01

    The purpose of this study was to combine gene expression profiles and clinical factors to provide a better prediction model of local control after chemoradiotherapy for advanced head and neck cancer. Gene expression data were available for a series of 92 advanced stage head and neck cancer patients treated with primary chemoradiotherapy. The effect of the Chung high-risk and Slebos HPV expression profiles on local control was analyzed in a model with age at diagnosis, gender, tumor site, tumor volume, T-stage and N-stage and HPV profile status. Among 75 patients included in the study, the only factors significantly predicting local control were tumor site (oral cavity vs. Pharynx, hazard ratio 4.2 [95% CI 1.4-12.5]), Chung gene expression status (high vs. Low risk profile, hazard ratio 4.4 [95% CI 1.5-13.3]) and HPV profile (negative vs. Positive profile, hazard ratio 6.2 [95% CI 1.7-22.5]). Chung high-risk expression profile and a negative HPV expression profile were significantly associated with increased risk of local recurrence after chemoradiotherapy in advanced pharynx and oral cavity tumors, independent of clinical factors. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas

    NARCIS (Netherlands)

    Muris, JJF; Cillessen, SAGM; Vos, W; van Houdt, IS; Kummer, JA; van Krieken, JHJM; Jiwa, NM; Jansen, PM; Kluin-Nelemans, HC; Ossenkoppele, GJ; Gundy, C; Meijer, CJLM; Oudejans, JJ

    2005-01-01

    We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoplosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive

  11. Aliskiren: a clinical profile

    Directory of Open Access Journals (Sweden)

    Roland E Schmieder

    2006-06-01

    Full Text Available Aliskiren is a novel oral antihypertensive agent, and the first in the new class of direct renin inhibitors. Here we review the key criteria that a new antihypertensive drug should possess, notably effective blood pressure lowering as monotherapy and combination therapy, 24-hour blood pressure control, safety and tolerability, end-organ protective effects, minimal drug interaction and efficacy during long-term use.Aliskiren fulfils key criteria for a new antihypertensive agent.The drug demonstrates effective blood lowering in a number of studies as monotherapy and in combination with a thiazide diuretic (hydrochlorothiazide, an angiotensin-converting enzyme inhibitor (ramipril and a calcium channel blocker (amlodipine. Other studies applying ambulatory blood pressure monitoring show that aliskiren maintains blood pressure control for more than 24 hours. Aliskiren, 150 mg and 300 mg have demonstrated a placebo-like safety and tolerability profile, with no interactions with a wide range of commonly used drugs. Three studies (AVOID, ALOFT and ALLAY are ongoing properties. with aliskiren to assess end-organ protective properties.

  12. Aliskiren: A clinical profile

    Directory of Open Access Journals (Sweden)

    Roland E Schmieder

    2006-06-01

    Full Text Available Aliskiren is a novel oral antihypertensive agent, and the first in the new class of direct renin inhibitors. Here we review the key criteria that a new antihypertensive drug should possess, notably effective blood pressure lowering as monotherapy and combination therapy, 24-hour blood pressure control, safety and tolerability end-organ protective effects, minimal drug interaction and efficacy during long-term use. Aliskiren fulfils key criteria for a new antihypertensive agent. The drug demonstrates effective blood lowering in a number of studies as monotherapy and in combination with a thiazide diuretic (hydrochlorothiazide, an angiotensin-converting enzyme inhibitor (ramipril and a calcium channel blocker (amlodipine. Other studies applying ambulatory blood pressure monitoring show that aliskiren maintains blood pressure control for more than 24 hours. Aliskiren, 150 mg and 300 mg have demonstrated a placebo-like safety and tolerability profile with no interactions with a wide range of commonly used drugs. Three studies (AVOID, ALOFT and ALLAY are ongoing with aliskiren to assess end-organ protective properties.

  13. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Young, Ken H; Leroy, Karen; Møller, Michael Boe

    2008-01-01

    The purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients and the overall survival (OS) of pati...

  14. Geographic Profiling: Knowledge Through Prediction

    Science.gov (United States)

    2014-06-01

    acts. In general, geographic profiling “is based on crime pattern, routine activity, and rational choice theories from environmental criminology , a...Information Systems and Crime Analysis , ed. Fahui Wang (Hershey, PA: Idea Group, 2005), 104. 3 models to the actual outcomes and determine the...order to construct a geographic profile, the coordinates of crime scenes are entered into a software analysis program that contains an algorithm known

  15. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...... of subcutaneous fibrosis in breast cancer patients will be presented and discussed in relation to possible future studies in radiogenomics. One important and necessary basis for future studies is the collection of carefully designed clinical studies with the accrual of very large numbers of patients (the ESTRO...

  16. Motion Predicts Clinical Callus Formation

    Science.gov (United States)

    Elkins, Jacob; Marsh, J. Lawrence; Lujan, Trevor; Peindl, Richard; Kellam, James; Anderson, Donald D.; Lack, William

    2016-01-01

    Background: Mechanotransduction is theorized to influence fracture-healing, but optimal fracture-site motion is poorly defined. We hypothesized that three-dimensional (3-D) fracture-site motion as estimated by finite element (FE) analysis would influence callus formation for a clinical series of supracondylar femoral fractures treated with locking-plate fixation. Methods: Construct-specific FE modeling simulated 3-D fracture-site motion for sixty-six supracondylar femoral fractures (OTA/AO classification of 33A or 33C) treated at a single institution. Construct stiffness and directional motion through the fracture were investigated to assess the validity of construct stiffness as a surrogate measure of 3-D motion at the fracture site. Callus formation was assessed radiographically for all patients at six, twelve, and twenty-four weeks postoperatively. Univariate and multivariate linear regression analyses examined the effects of longitudinal motion, shear (transverse motion), open fracture, smoking, and diabetes on callus formation. Construct types were compared to determine whether their 3-D motion profile was associated with callus formation. Results: Shear disproportionately increased relative to longitudinal motion with increasing bridge span, which was not predicted by our assessment of construct stiffness alone. Callus formation was not associated with open fracture, smoking, or diabetes at six, twelve, or twenty-four weeks. However, callus formation was associated with 3-D fracture-site motion at twelve and twenty-four weeks. Longitudinal motion promoted callus formation at twelve and twenty-four weeks (p = 0.017 for both). Shear inhibited callus formation at twelve and twenty-four weeks (p = 0.017 and p = 0.022, respectively). Titanium constructs with a short bridge span demonstrated greater longitudinal motion with less shear than did the other constructs, and this was associated with greater callus formation (p callus formation, while shear inhibited

  17. Epidemiology, clinical profile and factors, predicting final visual outcome of pediatric ocular trauma in a tertiary eye care center of Central India

    Directory of Open Access Journals (Sweden)

    Satendra Singh

    2017-01-01

    Full Text Available Purpose: Ocular trauma constitutes an important cause of preventable visual morbidity worldwide. This study was done to study the incidence, sociodemographic pattern, and clinical profile of ocular trauma in pediatric age group. Also to evaluate the factors influencing final visual outcome in these patients. Methods: This was a prospective interventional study concerning ocular trauma in pediatric patients up to 16 years of age of either sex. Various variables having an impact on final visual outcome were studied, and results were analyzed using statistical indices – relative risk, Chi-square test, P value, and linear regression analysis. Results: A total of 220 cases of trauma were evaluated with the mean age being 8.74 ± 3.93 years, males were predominantly affected and open globe injuries outnumbered blunt injuries. Penetrating injuries accounted for 67.79% cases of open globe injury, rupture being the least (2.54%. Stepwise multiple linear regression analysis executed, showed the best predictors in the descending order for final visual outcome were presenting visual acuity, size of corneal tear, type of injury, zone of injury, time period between injury and treatment with a variance of 35.9%, 6.3%, 5.3%, 3.7%, and 2.7%, respectively. All above variables were also found to be statistically significant (P < 0.05 on Chi-square test. Conclusion: We report the first study on the epidemiology and clinical outcomes of pediatric ocular trauma in central India. Poor initial Visual Acuity and posterior segment involvement adversely affect the visual outcome. Early medical treatment and globe-salvaging repair should be done in all eyes suffering from trauma.

  18. Genetic profiling to predict recurrence of early cervical cancer.

    Science.gov (United States)

    Lee, Yoo-Young; Kim, Tae-Joong; Kim, Ji-Young; Choi, Chel Hun; Do, In-Gu; Song, Sang Yong; Sohn, Insuk; Jung, Sin-Ho; Bae, Duk-Soo; Lee, Jeong-Won; Kim, Byoung-Gie

    2013-12-01

    Recurrence is the major cause of death in early cervical cancer. We compared the prediction powers for disease recurrence between the gene set prognostic model and the clinical prognostic model. A gene set model to predict disease free survival was developed using the cDNA-mediated annealing, selection, extension, and ligation (DASL) assay data set from a cohort of early cervical cancer patients who had been treated with radical surgery with or without adjuvant therapy. A clinical prediction model was also developed using the same cohort, and the ability of predicting recurrence from each model was compared. Adequate DASL assay profiles were obtained from 300 patients, and we selected 12 genes for the gene set model. When patients were categorized as having a low or high risk by the prognostic score, the Kaplan-Meier curve showed significantly different recurrence rates between the two groups. The clinical model was developed using FIGO stage and post-surgical pathological findings. In multivariate Cox regression analysis of prognostic models, the gene set prognostic model showed a higher hazard ratio than that of the clinical prognostic model. The genetic quantitative approach may be better in predicting recurrence in early cervical cancer patients. © 2013 Elsevier Inc. All rights reserved.

  19. Profiling critical cancer gene mutations in clinical tumor samples.

    Directory of Open Access Journals (Sweden)

    Laura E MacConaill

    2009-11-01

    Full Text Available Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting.We developed and implemented an optimized mutation profiling platform ("OncoMap" to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact.Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.

  20. Clinical pharmacokinetic profile of modafinil.

    Science.gov (United States)

    Robertson, Philmore; Hellriegel, Edward T

    2003-01-01

    Modafinil is a unique wake-promoting agent for oral administration. Its pharmacological properties are distinct from those of other CNS agents, and it selectively targets neuronal pathways in the sleep/wake centres of the brain. After single or multiple oral doses, modafinil is readily absorbed, reaching maximum plasma concentrations at 2-4 hours after administration and pharmacokinetic steady state within 2-4 days. Its pharmacokinetics are dose-independent between 200 and 600 mg/day. The elimination half-life is approximately 12-15 hours, which is largely reflective of the pharmacokinetics of the longer-lived l-enantiomer. Modafinil is primarily eliminated via metabolism, mainly in the liver, with subsequent excretion in the urine. Less than 10% of the dose is excreted as unchanged drug. Metabolism is largely via amide hydrolysis, with lesser contributions from cytochrome P450 (CYP)-mediated oxidative pathways. In patients who are renally or hepatically compromised, the elimination processes can be slowed, and in a similar manner (although to a lesser extent), elimination in the elderly may be reduced due to normal effects of aging. Because modafinil is administered concomitantly with other medications, the potential for metabolic drug-drug interactions has been examined both in vitro and in vivo. In vitro, modafinil was observed to produce a reversible inhibition of CYP2C19 in human liver microsomes. It also caused a small, but concentration-dependent, induction of CYP1A2, CYP2B6 and CYP3A4 activities and suppression of CYP2C9 activity in primary cultures of human hepatocytes. Clinical studies have been conducted to examine the potential for interactions with methylphenidate, dexamfetamine, warfarin, ethinylestradiol and triazolam. The only substantive interactions observed were with ethinylestradiol and triazolam, apparently through induction of CYP3A4, primarily in the gastrointestinal system. Overall, the results of the interaction studies suggest that

  1. Adaptive method for electron bunch profile prediction

    Directory of Open Access Journals (Sweden)

    Alexander Scheinker

    2015-10-01

    Full Text Available We report on an experiment performed at the Facility for Advanced Accelerator Experimental Tests (FACET at SLAC National Accelerator Laboratory, in which a new adaptive control algorithm, one with known, bounded update rates, despite operating on analytically unknown cost functions, was utilized in order to provide quasi-real-time bunch property estimates of the electron beam. Multiple parameters, such as arbitrary rf phase settings and other time-varying accelerator properties, were simultaneously tuned in order to match a simulated bunch energy spectrum with a measured energy spectrum. The simple adaptive scheme was digitally implemented using matlab and the experimental physics and industrial control system. The main result is a nonintrusive, nondestructive, real-time diagnostic scheme for prediction of bunch profiles, as well as other beam parameters, the precise control of which are important for the plasma wakefield acceleration experiments being explored at FACET.

  2. Computational lipidology: predicting lipoprotein density profiles in human blood plasma.

    Directory of Open Access Journals (Sweden)

    Katrin Hübner

    2008-05-01

    Full Text Available Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond "bad" and "good" cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL, we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile is calculated. As our main results, we (i successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS, revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia.

  3. Slurry discharge management-beach profile prediction

    Energy Technology Data Exchange (ETDEWEB)

    Bravo, R.; Nawrot, J.R. [Southern Illinois University at Carbondale, Carbondale, IL (United States). Dept. of Civil Engineering

    1996-11-01

    Mine tailings dams are embankments used by the mining industry to retain the tailings products after the mineral preparation process. Based on the acid-waste stereotype that all coal slurry is acid producing, current reclamation requires a four foot soil cover for inactive slurry disposal areas. Compliance with this requirement is both difficult and costly and in some case unnecessary, as not all the slurry, or portions of slurry impoundments are acid producing. Reduced costs and recent popularity of wetland development has prompted many operators to request reclamation variances for slurry impoundments. Waiting to address slurry reclamation until after the impoundment is full, limits the flexibility of reclamation opportunities. This paper outlines a general methodology to predict the formation of the beach profile for mine tailings dams, by the discharge volume and location of the slurry into the impoundment. The review is presented under the perspective of geotechnical engineering and waste disposal management emphasizing the importance of pre-planning slurry disposal land reclamation. 4 refs., 5 figs.

  4. Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Ma, Zihao; Carr, Steven A.; Mertins, Philipp; Zhang, Hui; Zhang, Zhen; Chan, Daniel W.; Ellis, Matthew J. C.; Townsend, R. Reid; Smith, Richard D.; McDermott, Jason E.; Chen, Xian; Paulovich, Amanda G.; Boja, Emily S.; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Rodland, Karin D.; Liebler, Daniel C.; Zhang, Bing

    2016-11-11

    Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

  5. Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis

    Science.gov (United States)

    Sweeney, Shannon R; Kavanaugh, Arthur; Lodi, Alessia; Wang, Bo; Boyle, David; Tiziani, Stefano; Guma, Monica

    2016-01-01

    Objective: To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire 1H-NMR and ultra high pressure liquid chromatography (UPLC)–MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that 1H-NMR and UPLC–MS/MS may be promising tools for predicting response to rituximab. PMID:27651926

  6. Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis.

    Science.gov (United States)

    Sweeney, Shannon R; Kavanaugh, Arthur; Lodi, Alessia; Wang, Bo; Boyle, David; Tiziani, Stefano; Guma, Monica

    2016-01-01

    To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire (1)H-NMR and ultra high pressure liquid chromatography (UPLC)-MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that (1)H-NMR and UPLC-MS/MS may be promising tools for predicting response to rituximab.

  7. Copperhead envenomations: clinical profiles of three different subspecies.

    Science.gov (United States)

    Keyler, D E; Vandevoort, J T

    1999-06-01

    Copperhead envenomation cases reported in the literature frequently lack identification of the subspecies of copperhead responsible for the envenomation. Whether subspecific identity would be useful in predicting possible different toxicity profiles may have clinical relevance. We report here the clinical profiles from envenomations involving 3 different subspecies of captive adult copperhead snakes--the southern copperhead (Agkistrodon contortrix contortrix), the northern copperhead (Agkistrodon contortrix mokasen), and the broad-banded copperhead (Agkistrodon contortrix laticinctus). The bites occurred in the north-central region of the US where none of these subspecies are endemic and involved a professional and 2 amateur herpetologists. The victims were adult males with no previous history of venomous snake bite, and all bites were evidenced by fang puncture marks to their index finger or thumb. Envenomations from the broad-banded and northern copperhead subspecies caused localized symptoms of pain, edema and ecchymosis. In addition to these symptoms, southern copperhead envenomation resulted in a more severe clinical toxicity profile as evidenced by propulsive emesis, diarrhea and hematuria. Whether these differences in observed clinical toxicity were the result of unique subspecific venom pharmacological actions is an interesting question. However, independent of the copperhead subspecies involved, conservative medical management was effective in each case.

  8. Gene-expression profiling to predict responsiveness to immunotherapy.

    Science.gov (United States)

    Jamieson, N B; Maker, A V

    2017-03-01

    Recent clinical successes with immunotherapy have resulted in expanding indications for cancer therapy. To enhance antitumor immune responses, and to better choose specific strategies matched to patient and tumor characteristics, genomic-driven precision immunotherapy will be necessary. Herein, we explore the role that tumor gene-expression profiling (GEP) may have in the prediction of an immunotherapeutic response. Genetic markers associated with response to immunotherapy are addressed as they pertain to the tumor genomic landscape, the extent of DNA damage, tumor mutational load and tumor-specific neoantigens. Furthermore, genetic markers associated with resistance to checkpoint blockade and relapse are reviewed. Finally, the utility of GEP to identify new tumor types for immunotherapy and implications for combinatorial strategies are summarized.

  9. Clinical studies of biomarkers in suicide prediction

    OpenAIRE

    Jokinen, Jussi

    2007-01-01

    Suicide is a major clinical problem in psychiatry and suicidal behaviours can be seen as a nosological entity per se. Predicting suicide is difficult due to its low base-rate and the limited specificity of clinical predictors. Prospective biological studies suggest that dysfunctions in the hypothalamo pituitary adrenal (HPA) axis and the serotonergic system have predictive power for suicide in mood disorders. Suicide attempt is the most robust clinical predictor making suici...

  10. Gene Expression Profiling Predicts Survival in Conventional Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  11. Gene expression profiling predicts survival in conventional renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hongjuan Zhao

    2006-01-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  12. Friedreich ataxia: dysarthria profile and clinical data.

    Science.gov (United States)

    Brendel, Bettina; Ackermann, Hermann; Berg, Daniela; Lindig, Tobias; Schölderle, Theresa; Schöls, Ludger; Synofzik, Matthis; Ziegler, Wolfram

    2013-08-01

    Friedreich ataxia (FRDA) is the most frequent recessive ataxia in the Western world. Dysarthria is a cardinal feature of FRDA, often leading to severe impairments in daily functioning, but its exact characteristics are only poorly understood so far. We performed a comprehensive evaluation of dysarthria severity and the profile of speech motor deficits in 20 patients with a genetic diagnosis of FRDA based on a carefully selected battery of speaking tasks and two widely used paraspeech tasks, i.e., oral diadochokinesis and sustained vowel productions. Perceptual ratings of the speech samples identified respiration, voice quality, voice instability, articulation, and tempo as the most affected speech dimensions. Whereas vocal instability predicted ataxia severity, tempo turned out as a significant correlate of disease duration. Furthermore, articulation predicted the overall intelligibility score as determined by a systematic speech pathology assessment tool. In contrast, neurologists' ratings of intelligibility--a component of the "Scale for the Assessment and Rating of Ataxia"--were found to be related to perceived speech tempo. Obviously, clinicians are more sensitive to slowness of speech than to any other feature of spoken language during dysarthria evaluation. Our results suggest that different components of speech production and trunk/limb motor functions are differentially susceptible to FRDA pathology. Furthermore, evidence emerged that paraspeech tasks do not allow for an adequate scaling of speech deficits in FRDA.

  13. Hypertensive crisis: clinical-epidemiological profile.

    Science.gov (United States)

    Vilela-Martin, José Fernando; Vaz-de-Melo, Renan Oliveira; Kuniyoshi, Cristina Hiromi; Abdo, André Neder Ramires; Yugar-Toledo, Juan Carlos

    2011-03-01

    Hypertensive crisis (HC) stands out as one type of acute elevation in blood pressure (BP) and can manifest as hypertensive emergency (HE-with target-organ damage (TOD)) or hypertensive urgency (HU-without TOD), usually accompanied by levels of diastolic BP ≥120 mmHg. The aim of this study was to characterize the clinical-epidemiological profile of HC over the course of 1 year in a university reference hospital and perform a review of the literature. The study was a cross-sectional study, conducted over a period of 1 year (2006) in 362 patients who presented for treatment at the emergency hospital with HC, as described above. Among all patients examined, 231 individuals met the criteria for HE and 131 met the criteria for HU. Patients with HE were older (Phypertension. © 2011 The Japanese Society of Hypertension All rights reserved

  14. A predictable Java profile - rationale and implementations

    DEFF Research Database (Denmark)

    Søndergaard, Hans; Bøgholm, Thomas; Hansen, Rene Rydhof

    2009-01-01

    , and is directly inspired by interactions with the Open Group on their on-going work on a safety critical Java profile (JSR-302). The main contribution is an arrangement of the class hierarchy such that the proposal is a generalization of Real-Time Specification for Java (RTSJ). A further contribution...... is to integrate the mission concept as a handler, such that mission memory becomes a handler private memory and such that mission initialization and finalization are scheduled activities. Two implementations are presented: one directly on an open source JVM using Xenomai and another, based on delegation...

  15. Predicting Academic Success Using Admission Profiles

    Science.gov (United States)

    Davidovitch, Nitza; Soen, Dan

    2015-01-01

    This study, conducted at a tertiary education institution in Israel, following two previous studies, was designed to deal again with a question that is a topic of debate in Israel and worldwide: Is there justification for the approach that considers restrictive university admission policies an efficient tool for predicting students' success at the…

  16. CLINICAL PROFILE OF SNAKEBITE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Chandrashekar

    2015-07-01

    Full Text Available A retrospective study of 37 cases of snakebites admitted in the pediatrics wards, MVJ Medical College from January 2012 to December 2014 was done. A detailed history, a methodological clinical profile, established treatment and follow - up in the hospital was done for all the cases and recorded. There was definite male preponderance and all the patients were from rural background. Most of the bites occurred while playing or working away from home during evening times. Most of the patients did not receive first aid after the snakebite. This shows lack of aw areness of the first aid in the management of the snakebites in rural population. Most of the patients were admitted within 2 hours of the bite. Pain and swelling were the most common clinical manifestations. Other local manifestations included cellulitis and local necrosis. The neurological manifestations that were seen are ptosis and drowsiness followed by respiratory paralysis in few cases. In present study there were no cases of hypovolemic shock, intracerebral hemorrhage or DIC. All patients with signs of envenomation were given ASV according to the grading and progression of symptoms and signs. Mild early reactions were noticed in few cases, but in none of the cases there was severe reaction. Supportive treatment like IV fluids, tetanus toxoid, antibio tic coverage and anti - inflammatory drugs were given in all patients. Fasciotomy was the most common surgical intervention required. The mean duration of hospital stay in the present study was 6 days. There was no mortality in the present study

  17. The Reliability and Predictive Validity of the Stalking Risk Profile.

    Science.gov (United States)

    McEwan, Troy E; Shea, Daniel E; Daffern, Michael; MacKenzie, Rachel D; Ogloff, James R P; Mullen, Paul E

    2018-03-01

    This study assessed the reliability and validity of the Stalking Risk Profile (SRP), a structured measure for assessing stalking risks. The SRP was administered at the point of assessment or retrospectively from file review for 241 adult stalkers (91% male) referred to a community-based forensic mental health service. Interrater reliability was high for stalker type, and moderate-to-substantial for risk judgments and domain scores. Evidence for predictive validity and discrimination between stalking recidivists and nonrecidivists for risk judgments depended on follow-up duration. Discrimination was moderate (area under the curve = 0.66-0.68) and positive and negative predictive values good over the full follow-up period ( Mdn = 170.43 weeks). At 6 months, discrimination was better than chance only for judgments related to stalking of new victims (area under the curve = 0.75); however, high-risk stalkers still reoffended against their original victim(s) 2 to 4 times as often as low-risk stalkers. Implications for the clinical utility and refinement of the SRP are discussed.

  18. Revised prediction (estimation) of Cape Kennedy, Florida, wind speed profile

    Science.gov (United States)

    Guttman, N. B.; Crutcher, H. L.

    1975-01-01

    The prediction of the wind profile maximum speed at Cape Kennedy, Florida, is made for any selected calendar data. The prediction is based on a normal probability distribution model with 15 years of smoothed input data and is static in the sense that no dynamic principles of persistence or synoptic features are considered. Comparison with similar predictions based on 6 years of data shows the same general pattern, but the variability decreased with the increase of sample size.

  19. Clinical profile of distal renal tubular acidosis

    Directory of Open Access Journals (Sweden)

    Ratan Jha

    2011-01-01

    Full Text Available To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA, we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA, acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54% patients. Urological defect in children (22/44 and autoimmune disease in adults (11/52 were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR 60 mL/min (P <0.005. In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period.

  20. Cognitive and Motivational Profile Shape Predicts Mathematical Skills over and above Profile Level

    Science.gov (United States)

    Reimann, Giselle; Stoecklin, Markus; Lavallee, Kristen; Gut, Janine; Frischknecht, Marie-Claire; Grob, Alexander

    2013-01-01

    The interpretation of subtest profiles from intelligence testing remains popular among many practitioners who use subtest performance to draw diagnostic conclusions, in spite of criticism by some researchers, who point to the low reliability and predictive validity of subtest scores in predicting achievement outcomes. Prior research outlines two…

  1. Clinical profile of leprosy patients: a prospective study

    National Research Council Canada - National Science Library

    Thakkar, Sejal; Patel, Sangita V

    2014-01-01

    .... The present study was carried out to know the clinical profile of leprosy patients, concordance between clinical and histopathological diagnosis in cases of leprosy, and to assess the therapeutic...

  2. Clinical pharmacology profile of care in Hepatology clinic

    Directory of Open Access Journals (Sweden)

    Talita Rocha Passos

    Full Text Available Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as diabetes, hypertension and dyslipidemia. Most patients took their medication in the Basic Health Units. We found that 30% of patients use of more than five medications and the most prescribed were omeprazole 208 (42.3%, metformin 132 (26.8% and losartan 80 (16.3%. Because it is an adult/elderly population, with several comorbidities and polymedication, it is important to be aware of the rational use of medication. The multidisciplinary team is important in applying correct conducts for the safe use of medicines, to reduce the burden on health spending and improving the quality of life of patients.

  3. Clinical profile of acute flaccid paralysis

    Directory of Open Access Journals (Sweden)

    Naveed Mohsin

    2016-01-01

    Full Text Available Background and Aim: As a part of the Global Polio Eradication Program by the World Health Organization (WHO, 1988, surveillance of acute flaccid paralysis (AFP was an important public health activity in many countries. With nearing eradication of poliomyelitis, other causes of AFP are gaining importance in both children and adults. Our study was designed to know the clinical characteristics, and differential diagnosis of causes of AFP, including distribution by age, gender, and time. This was a prospective observational study. Materials and Methods: AFP cases were diagnosed on history and physical examination. The underlying etiology was ascertained by appropriate laboratory investigations such as arterial blood gas analysis, urinary pH, electrolytes, thyroid profile, electrophysiological studies, cerebrospinal fluid analysis, and imaging. Results: Between July 2010 and September 2012, 106 cases of AFP were enrolled. The mean age in males was 40.2 years (standard deviation [SD] 17.1 and the mean age in females was 33.4 years (SD 14.1. Males constituted 57.5% (61/106 and females constituted 42.5% (45/106. Out of 106 patients, 58 (54.7% were suffering from Guillain–Barré syndrome (GBS, 15 (14.2% from hypokalemic paralysis, 8 (7.5% from myasthenia gravis, 8 (7.5% from thiamine deficiency, 5 (4.7% from transverse myelitis, and 2 (1.9% from cord compression. Other diagnoses include acute motor axonal neuropathy (AMAN 3 (2.8%, acute disseminated encephalomyelitis 2 (1.9%, meningoencephalitis 2 (1.9%, diabetic polyneuropathy 2 (1.9%, and chemotherapy-induced neuropathy 1 (0.9%. Most cases 42/106 (39.6% were admitted during spring season. Conclusion: GBS was the most common cause of AFP in all age groups. Most AFP cases occurred during spring season. No case of polio myelitis was found.

  4. Insulin Resistance Predicts Atherogenic Lipoprotein Profile in Nondiabetic Subjects

    Directory of Open Access Journals (Sweden)

    Flávia De C. Cartolano

    2017-01-01

    Full Text Available Background. Atherogenic diabetes is associated with an increased cardiovascular risk and mortality in diabetic individuals; however, the impact of insulin resistance (IR in lipid metabolism in preclinical stages is generally underreported. For that, we evaluated the capacity of IR to predict an atherogenic lipid subfraction profile. Methods. Complete clinical evaluation and biochemical analysis (lipid, glucose profile, LDL, and HDL subfractions and LDL phenotype and size were performed in 181 patients. The impact of IR as a predictor of atherogenic lipoproteins was tested by logistic regression analysis in raw and adjusted models. Results. HDL-C and Apo AI were significantly lower in individuals with IR. Individuals with IR had a higher percentage of small HDL particles, lower percentage in the larger ones, and reduced frequency of phenotype A (IR = 62%; non-IR = 83%. IR individuals had reduced probability to have large HDL (OR = 0.213; CI = 0.999–0.457 and had twice more chances to show increased small HDL (OR = 2.486; CI = 1.341–7.051. IR was a significant predictor of small LDL (OR = 3.075; CI = 1.341–7.051 and atherogenic phenotype (OR = 3.176; CI = 1.469–6.867. Conclusion. IR, previously DM2 diagnosis, is a strong predictor of quantitative and qualitative features of lipoproteins directly associated with an increased atherogenic risk.

  5. What predicts performance during clinical psychology training?

    Science.gov (United States)

    Scior, Katrina; Bradley, Caroline E; Potts, Henry W W; Woolf, Katherine; de C Williams, Amanda C

    2014-06-01

    While the question of who is likely to be selected for clinical psychology training has been studied, evidence on performance during training is scant. This study explored data from seven consecutive intakes of the UK's largest clinical psychology training course, aiming to identify what factors predict better or poorer outcomes. Longitudinal cross-sectional study using prospective and retrospective data. Characteristics at application were analysed in relation to a range of in-course assessments for 274 trainee clinical psychologists who had completed or were in the final stage of their training. Trainees were diverse in age, pre-training experience, and academic performance at A-level (advanced level certificate required for university admission), but not in gender or ethnicity. Failure rates across the three performance domains (academic, clinical, research) were very low, suggesting that selection was successful in screening out less suitable candidates. Key predictors of good performance on the course were better A-levels and better degree class. Non-white students performed less well on two outcomes. Type and extent of pre-training clinical experience on outcomes had varied effects on outcome. Research supervisor ratings emerged as global indicators and predicted nearly all outcomes, but may have been biased as they were retrospective. Referee ratings predicted only one of the seven outcomes examined, and interview ratings predicted none of the outcomes. Predicting who will do well or poorly in clinical psychology training is complex. Interview and referee ratings may well be successful in screening out unsuitable candidates, but appear to be a poor guide to performance on the course. © 2013 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of the British Psychological Society.

  6. Predicting Post-Editor Profiles from the Translation Process

    DEFF Research Database (Denmark)

    Singla, Karan; Orrego-Carmona, David; Gonzales, Ashleigh Rhea

    2014-01-01

    The purpose of the current investigation is to predict post-editor profiles based on user behaviour and demographics using machine learning techniques to gain a better understanding of post-editor styles. Our study extracts process unit features from the CasMaCat LS14 database from the CRITT...

  7. Prediction of clinical change by ethological methods.

    Science.gov (United States)

    Bouhuys, A L; Beersma, D G; Van den Hoofdakker, R H

    1988-01-01

    The aim of this paper is to show that ethology may contribute to the search for early indicators of clinical changes in depression. Three studies are presented. One study deals with the prediction of treatment outcome over 10 weeks and the other two with the prediction of the acute clinical response to total sleep deprivation (TSD). In each study a number of behaviours were observed, as displayed during a baseline psychiatric interview by the patients as well as the psychiatrist. In this report, the predictive potency of directly observed behaviours is compared to the predictive value of global clinical measures of psychomotor activation. The behaviours of the patients were interpreted as "relational" and "nonrelational" behaviours. The relational behaviours (i.e., variation in looking, yes-nodding, gesturing) occurred less, the nonrelational behaviours (i.e., intensive body touching, head movements) occurred more in responders than in nonresponders to 10 weeks of treatment. Also in the TSD studies body touching was positively related to improvement. Global clinical assessment of psychomotor activation could not be related to outcome. The advantages of the observational methods are discussed.

  8. Prediction accuracy of soft tissue profile in orthognathic surgery.

    Science.gov (United States)

    Mankad, B; Cisneros, G J; Freeman, K; Eisig, S B

    1999-01-01

    The purpose of this study was to compare soft tissue prediction accuracy of model surgery combined with computer software prediction with that of computer software prediction alone and to assess surgical accuracy by comparing the immediate postsurgical cephalogram with the planned movement of skeletal hard tissue. The predicted and actual soft tissue changes and the corresponding skeletal changes of 16 patients were compared using the Quick Ceph Image cephalometric treatment simulation software. A custom analysis was created to measure the hard tissue and soft tissue changes that occurred as a result of the surgical procedure. On average, the predictions were not significantly different from the actual postsurgical profile changes. Surgical changes of hard tissues from presurgery to postsurgery were accurate as planned except for the position of N-ANS. All lower soft tissue points moved significantly during treatment. Quick Ceph Image offers a rapid and reliable method of profile prediction that does not require artistic skill. If predictions are interpreted with caution and transferred accurately to the model surgery, they can provide an excellent visual aid during presurgical treatment planning and patient presentation.

  9. Template-based quaternary structure prediction of proteins using enhanced profile-profile alignments.

    Science.gov (United States)

    Nakamura, Tsukasa; Oda, Toshiyuki; Fukasawa, Yoshinori; Tomii, Kentaro

    2017-11-27

    Proteins often exist as their multimeric forms when they function as so-called biological assemblies consisting of the specific number and arrangement of protein subunits. Consequently, elucidating biological assemblies is necessary to improve understanding of protein function. Template-Based Modeling (TBM), based on known protein structures, has been used widely for protein structure prediction. Actually, TBM has become an increasingly useful approach in recent years because of the increased amounts of information related to protein amino acid sequences and three-dimensional structures. An apparently similar situation exists for biological assembly structure prediction as protein complex structures in the PDB increase, although the inference of biological assemblies is not a trivial task. Many methods using TBM, including ours, have been developed for protein structure prediction. Using enhanced profile-profile alignments, we participated in the 12th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP12), as the FONT team (Group # 480). Herein, we present experimental procedures and results of retrospective analyses using our approach for the Quaternary Structure Prediction category of CASP12. We performed profile-profile alignments of several types, based on FORTE, our profile-profile alignment algorithm, to identify suitable templates. Results show that these alignment results enable us to find templates in almost all possible cases. Moreover, we have come to understand the necessity of developing a model selection method that provides improved accuracy. Results also demonstrate that, to some extent, finding templates of protein complexes is useful even for MEDIUM and HARD assembly prediction. © 2017 The Authors Proteins: Structure, Function and Bioinformatics Published by Wiley Periodicals, Inc.

  10. Meehl's contribution to clinical versus statistical prediction.

    Science.gov (United States)

    Grove, William M; Lloyd, Martin

    2006-05-01

    Paul E. Meehl's work on the clinical versus statistical prediction controversy is reviewed. His contributions included the following: putting the controversy center stage in applied psychology; clarifying concepts underpinning the debate (especially his crucial distinction between ways of gathering data and ways of combining them) as well as establishing that the controversy was real and not concocted, analyzing clinical inference from both theoretical and probabilistic points of view, and reviewing studies that compared the accuracy of these 2 methods of data combination. Meehl's (1954/1996) conclusion that statistical prediction consistently outperforms clinical judgment has stood up extremely well for half a century. His conceptual analyses have not been significantly improved since he published them in the 1950s and 1960s. His work in this area contains several citation classics, which are part of the working knowledge of all competent applied psychologists today.

  11. What predicts performance during clinical psychology training?

    Science.gov (United States)

    Scior, Katrina; Bradley, Caroline E; Potts, Henry W W; Woolf, Katherine; de C Williams, Amanda C

    2014-01-01

    Objectives While the question of who is likely to be selected for clinical psychology training has been studied, evidence on performance during training is scant. This study explored data from seven consecutive intakes of the UK's largest clinical psychology training course, aiming to identify what factors predict better or poorer outcomes. Design Longitudinal cross-sectional study using prospective and retrospective data. Method Characteristics at application were analysed in relation to a range of in-course assessments for 274 trainee clinical psychologists who had completed or were in the final stage of their training. Results Trainees were diverse in age, pre-training experience, and academic performance at A-level (advanced level certificate required for university admission), but not in gender or ethnicity. Failure rates across the three performance domains (academic, clinical, research) were very low, suggesting that selection was successful in screening out less suitable candidates. Key predictors of good performance on the course were better A-levels and better degree class. Non-white students performed less well on two outcomes. Type and extent of pre-training clinical experience on outcomes had varied effects on outcome. Research supervisor ratings emerged as global indicators and predicted nearly all outcomes, but may have been biased as they were retrospective. Referee ratings predicted only one of the seven outcomes examined, and interview ratings predicted none of the outcomes. Conclusions Predicting who will do well or poorly in clinical psychology training is complex. Interview and referee ratings may well be successful in screening out unsuitable candidates, but appear to be a poor guide to performance on the course. Practitioner points While referee and selection interview ratings did not predict performance during training, they may be useful in screening out unsuitable candidates at the application stage High school final academic performance

  12. Clinical Profile Of Atopic Dermatitis In Benin City, Nigeria | Onunu ...

    African Journals Online (AJOL)

    Conclusion: The clinical characteristics of atopic dermatitis in our study population were similar to the pattern in other parts of the world. There is need for increased awareness of its importance as a cause of morbidity especially in children. Keywords: Atopic dermatitis, Clinical profile,Nigeria. Nigerian Journal of Clinical ...

  13. [Profile of clinical trials enrolling Brazilian children].

    Science.gov (United States)

    Vieira, Jean Mendes de Lucena; Lima, Elisangela da Costa; Land, Marcelo Gerardin Poirot; Ventura, Miriam; Coelho, Helena Lutescia Luna

    2017-06-12

    This study aimed to characterize the clinical trials with medicines enrolling Brazilian children and adolescents, registered in the databases of Clinical Trials and the Brazilian Clinical Trials Network (ReBEC) from 1994 to 2014. Only 462 clinical trials enrolled Brazilian children and adolescents. There was an increase in registrations beginning in 2003, with an important drop in 2011. Among these trials, 35.5% were hosted in Brazil. The international clinical trials were mostly conducted by North American companies. In both cases, multinational industry was the principal source of funding. The clinical trials were predominantly phase III with injectable and solid oral pharmaceutical forms of antiviral drugs. Domestic clinical trials showed wider variation in the pharmaceutical forms and higher percentage of liquid formulations, when compared to the international trials. In addition to heavy external dependence for conducting clinical trials, the study emphasized the challenge for pediatric care in Brazil, which presents epidemiological peculiarities in an environment prone to the use of unlicensed medicines for children.

  14. In silico pKa prediction and ADME profiling.

    Science.gov (United States)

    Cruciani, Gabriele; Milletti, Francesca; Storchi, Loriano; Sforna, Gianluca; Goracci, Laura

    2009-11-01

    Improving the ADME profile of drug candidates is a critical step in lead optimization, and because pKa affects most ADME properties such as lipophilicity, solubility, and metabolism, it is extremely advantageous to predict pKa in order to guide the design of new compounds. However, accurately (designed for computational and medicinal chemists to predict the pKa values of organic compounds. Here, we present the major issues considered when we developed MoKa, such as the accurate selection of training data, the fundamentals of the methodology (which has also been extended to predict protein pKa), the treatment of multiprotic compounds, and the selection of the dominant tautomer for the calculation. Last, we illustrate some specific applications of MoKa to predict solubility, lipophilicity, and metabolism.

  15. Physiotherapy clinical educators' perceptions and experiences of clinical prediction rules.

    Science.gov (United States)

    Knox, Grahame M; Snodgrass, Suzanne J; Rivett, Darren A

    2015-12-01

    Clinical prediction rules (CPRs) are widely used in medicine, but their application to physiotherapy practice is more recent and less widespread, and their implementation in physiotherapy clinical education has not been investigated. This study aimed to determine the experiences and perceptions of physiotherapy clinical educators regarding CPRs, and whether they are teaching CPRs to students on clinical placement. Cross-sectional observational survey using a modified Dillman method. Clinical educators (n=211, response rate 81%) supervising physiotherapy students from 10 universities across 5 states and territories in Australia. Half (48%) of respondents had never heard of CPRs, and a further 25% had never used CPRs. Only 27% reported using CPRs, and of these half (51%) were rarely if ever teaching CPRs to students in the clinical setting. However most respondents (81%) believed CPRs assisted in the development of clinical reasoning skills and few (9%) were opposed to teaching CPRs to students. Users of CPRs were more likely to be male (pphysiotherapy (pphysiotherapy clinical practice. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  16. Bayesian prediction of RNA translation from ribosome profiling.

    Science.gov (United States)

    Malone, Brandon; Atanassov, Ilian; Aeschimann, Florian; Li, Xinping; Großhans, Helge; Dieterich, Christoph

    2017-04-07

    Ribosome profiling via high-throughput sequencing (ribo-seq) is a promising new technique for characterizing the occupancy of ribosomes on messenger RNA (mRNA) at base-pair resolution. The ribosome is responsible for translating mRNA into proteins, so information about its occupancy offers a detailed view of ribosome density and position which could be used to discover new translated open reading frames (ORFs), among other things. In this work, we propose Rp-Bp, an unsupervised Bayesian approach to predict translated ORFs from ribosome profiles. We use state-of-the-art Markov chain Monte Carlo techniques to estimate posterior distributions of the likelihood of translation of each ORF. Hence, an important feature of Rp-Bp is its ability to incorporate and propagate uncertainty in the prediction process. A second novel contribution is automatic Bayesian selection of read lengths and ribosome P-site offsets (BPPS). We empirically demonstrate that our read length selection technique modestly improves sensitivity by identifying more canonical and non-canonical ORFs. Proteomics- and quantitative translation initiation sequencing-based validation verifies the high quality of all of the predictions. Experimental comparison shows that Rp-Bp results in more peptide identifications and proteomics-validated ORF predictions compared to another recent tool for translation prediction. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Clinical profile of cyanotic congenital heart disease in neonatal ...

    African Journals Online (AJOL)

    Ashraf Abou-Taleb

    2016-02-01

    % of congenital heart defects and has a high morbidity and mortality in neonates. Objective: The aim of this work was to study clinical profile and available therapeutic modalities used in the management of CCHD. Subjects ...

  18. The demographic, clinical and forensic profile of offenders ...

    African Journals Online (AJOL)

    The demographic, clinical and forensic profile of offenders diagnosed with epilepsy referred to the Free State Psychiatric Complex Observation Unit in terms of section 77 and/or 78 of the Criminal Procedure Act 51 of 1977.

  19. Health profiles of foreigners attending primary care clinics in Malaysia

    National Research Council Canada - National Science Library

    Ab Rahman, Norazida; Sivasampu, Sheamini; Mohamad Noh, Kamaliah; Khoo, Ee Ming

    2016-01-01

    .... Little is known about the health profiles of foreign population in Malaysia. The aim of this study was to provide a detailed description of the health problems presented by foreigners attending primary care clinics in Malaysia...

  20. Random Subspace Aggregation for Cancer Prediction with Gene Expression Profiles

    Directory of Open Access Journals (Sweden)

    Liying Yang

    2016-01-01

    Full Text Available Background. Precisely predicting cancer is crucial for cancer treatment. Gene expression profiles make it possible to analyze patterns between genes and cancers on the genome-wide scale. Gene expression data analysis, however, is confronted with enormous challenges for its characteristics, such as high dimensionality, small sample size, and low Signal-to-Noise Ratio. Results. This paper proposes a method, termed RS_SVM, to predict gene expression profiles via aggregating SVM trained on random subspaces. After choosing gene features through statistical analysis, RS_SVM randomly selects feature subsets to yield random subspaces and training SVM classifiers accordingly and then aggregates SVM classifiers to capture the advantage of ensemble learning. Experiments on eight real gene expression datasets are performed to validate the RS_SVM method. Experimental results show that RS_SVM achieved better classification accuracy and generalization performance in contrast with single SVM, K-nearest neighbor, decision tree, Bagging, AdaBoost, and the state-of-the-art methods. Experiments also explored the effect of subspace size on prediction performance. Conclusions. The proposed RS_SVM method yielded superior performance in analyzing gene expression profiles, which demonstrates that RS_SVM provides a good channel for such biological data.

  1. Prevalence and clinical profile of fungal rhinosinusitis

    OpenAIRE

    Suresh, Sandeep; Arumugam, Dayanand; Zacharias, George; Palaninathan, Sengottaiah; Vishwanathan, Ravisankar; Venkatraman, Vaidyanathan

    2016-01-01

    Background: There are only a few landmark studies from the Indian subcontinent on fungal rhinosinusitis. The lack of awareness among clinicians regarding the varying clinical presentations of fungal rhinosinusitis prompted us to undertake this study. Objective: To determine the prevalence, etiologic basis, clinical features, radiologic features, and microscopic features of fungal rhinosinusitis, and to evaluate the various treatment modalities available. Methods: This was a prospective study ...

  2. Prevalence and clinical profile of fungal rhinosinusitis.

    Science.gov (United States)

    Suresh, Sandeep; Arumugam, Dayanand; Zacharias, George; Palaninathan, Sengottaiah; Vishwanathan, Ravisankar; Venkatraman, Vaidyanathan

    2016-01-01

    There are only a few landmark studies from the Indian subcontinent on fungal rhinosinusitis. The lack of awareness among clinicians regarding the varying clinical presentations of fungal rhinosinusitis prompted us to undertake this study. To determine the prevalence, etiologic basis, clinical features, radiologic features, and microscopic features of fungal rhinosinusitis, and to evaluate the various treatment modalities available. This was a prospective study in which evaluation of 100 patients with chronic rhinosinusitis was done. Specimens collected were subjected to both microbiology and pathologic examination; data collected, including clinical and radiologic features, were analyzed by the Pearson χ(2) test and Fisher's exact test. The prevalence of fungal rhinosinusitis in our study was 30% (n = 30). Mucor was the most commonly isolated species (n = 15 [50%]) of fungus. Pathologic examination had a higher sensitivity (76.67%) compared with microbiology tests (50%) in the diagnosis of fungal rhinosinusitis. Fungus ball (n = 14 [46.6%]) was the most prevalent entity in the spectrum of fungal rhinosinusitis. Forty percent of cases (n = 12) were of invasive fungal rhinosinusitis. The prevalence of fungal rhinosinusitis was higher among individuals who were immunocompetent (n = 17 [56.6%]). Of patients who were immunocompromised, 84.6% (n = 11) had mucormycosis. Unilateral involvement of paranasal sinuses was more in favor of fungal etiology. Complications were more common in fungal rhinosinusitis caused by Mucor species. Mucormycosis, a rare clinical entity, in subjects who were immunocompetent, had a high prevalence in our study.

  3. Clinical profile and pattern of adenoid hypertrophy among children ...

    African Journals Online (AJOL)

    Introduction: The objective of this study was to determine the pattern, clinical profile and surgical intervention in children presenting with adenoids hypertrophy in a private hospital. Methods: The study was conducted at the general pediatric clinic of a private hospital in Enugu, south east Nigeria in collaboration with a ...

  4. Clinical features and antinuclear antibodies profile among adults ...

    African Journals Online (AJOL)

    Introduction: Limited data is available regarding the clinical manifestations and pattern of Systemic Lupus Erythematosus (SLE) in Sudan. This study aimed to determine the clinical manifestations and Antinuclear Antibodies (ANA) profile among Sudanese adults with SLE and lupus nephritis (LN). Methods: A descriptive ...

  5. Comparison of clinical profiles and treatment outcomes between ...

    African Journals Online (AJOL)

    a dearth of information on the clinical status of this group in low-income countries. ... Key words: Vagrant; mental illness; clinical profile; outcome; Nigeria ... It is a World Health. Organization (WHO) collaborating centre for training and research in mental health. The hospital plays a vital role in mental health care for patients ...

  6. Clinical Profile of Vitiligo in North India

    Directory of Open Access Journals (Sweden)

    R V Koranne

    1986-01-01

    Full Text Available A clinical analysis of L50 patients having vitiligo revealed the incidence among new patients to be 1.25%. The male /female ratio was 1.3:1. Patients below the age of 30 years constituted 85%. Family history of vitiligo was available in 240/o. The different morphologic, Patterns consisted of vitiligo vulgaris (90 cases, vitiligo areata (22 cases, vitiligo acro-facialis (11 cases, vitiligo univers (11 cases , vitiligo mucoaae (9 cases,and vitiligo zosteriformis (7 cases. Association with diabetes meffitus (5 cases, alopecia areata (4 cases, Hashimoto′s thyroiditis (1 case and pemphigus vulgaris ( 1 case was observed.

  7. Clinical profile of subacute sclerosing panencephalitis.

    Science.gov (United States)

    Akram, Muhammad; Naz, Farrah; Malik, Akbar; Hamid, Haroon

    2008-08-01

    To describe the clinical manifestations of subacute sclerosing panencephalitis in children. Case series. This study was conducted in the Department of Neurology at The Children's Hospital and the Institute of Child Health, Lahore, from April 2005 to April 2007. Fifty patients were diagnosed as subacute sclerosing panencephalitis during the study period. Their diagnosis was based on a detailed history, clinical examination, presence of antimeasles antibodies in Cerebrospinal Fluid (CSF) and typical electroencephalogram (EEG). The findings were described as average, mean and percentages. Fifty patients were included in this study. The average age of the patients was 8 years. Thirty-eight (76%) were males and 12 (24%) were females. The average duration of symptoms before presentation was 66.72 days. History of measles infection was present in 31 patients (62%) and measles vaccination in 43 patients (86%). Motor regression was present in all (100%) patients and cognition decline in 43 patients (86%). Seizures were focal (10%), generalized tonicclonic (16%) and myoclonic (74%). Burst-suppression pattern Electroencephalogram (EEG) and the antimeasles antibody in CSF were positive in 100% of patients. SSPE is an indicator of high incidence of measles infection among the paediatric population even among vaccinated children. Males are more common sufferers. SSPE can present with different types of seizures, cognition decline and motor regression being supported by suggestive EEG and presence of anti-measles antibodies in CSF.

  8. Clinical profile of patients with fibromyalgia syndrome

    Directory of Open Access Journals (Sweden)

    Andrei Pereira Pernambuco

    Full Text Available Abstract Introduction: The new diagnostic criteria for fibromyalgia (FM include the presence of chronic, widespread pain associated with other symptoms such as fatigue, sleep disturbance, anxiety and depression. All these symptoms should be considered when thinking and clinical decision making of physiotherapists dealing with FM. However, it is clear that the other symptoms that accompany the pain are often neglected. Objective: To measure the levels of fatigue, sleep disturbances, anxiety and depression in patients with FM and compare them to levels found in healthy controls. Methods: Forty-six women diagnosed with FM and 30 healthy controls participated in the study. The levels of each of the symptoms were assessed by four validated questionnaires in Brazil (Piper Fatigue Scale - Revised, Pittsburgh Sleep Quality Index, Beck Anxiety Inventory and the Beck Depression Inventory. Statistical analysis was performed using GraphPad Prism software and all tests used a significance level of 5% (α = 0.05. Results: FM patients had significantly elevated levels of fatigue (p = 0.0005, sleep disturbances (p = 0.003, anxiety (p = 0.0012 and depression (p = 0.0003 compared to healthy controls. Symptoms fatigue and depression correlated strongly and positively with one another and with other symptoms evaluated. Conclusion: The other symptoms that comprise the clinical picture of FM need be considered not only in order to recover the health of patients, but above all in an attempt to preserve it and promote it.

  9. Prediction of propagated wave profiles based on point measurement

    Directory of Open Access Journals (Sweden)

    Sang-Beom Lee

    2014-03-01

    Full Text Available This study presents the prediction of propagated wave profiles using the wave information at a fixed point. The fixed points can be fixed in either space or time. Wave information based on the linear wave theory can be expressed by Fredholm integral equation of the first kinds. The discretized matrix equation is usually an ill-conditioned system. Tikhonov regularization was applied to the ill-conditioned system to overcome instability of the system. The regularization parameter is calculated by using the L-curve method. The numerical results are compared with the experimental results. The analysis of the numerical computation shows that the Tikhonov regularization method is useful.

  10. Predicting At-Risk Patient Profiles from Big Prescription Data

    OpenAIRE

    Genevès, Pierre; Calmant, Thomas; Layaïda, Nabil; Lepelley, Marion; Artemova, Svetlana; Bosson, Jean-Luc

    2017-01-01

    We show how the analysis of very large amounts of drug prescription data make it possible to detect, on the day of hospital admission, patients at risk of developing complications during their hospital stay. We explore, for the first time, to which extent volume and variety of big prescription data help in constructing predictive models for the automatic detection of at-risk profiles.Our methodology is designed to validate our claims that: (1) drug prescription data on the day of admission co...

  11. [Endometrial cancer: Predictive models and clinical impact].

    Science.gov (United States)

    Bendifallah, Sofiane; Ballester, Marcos; Daraï, Emile

    2017-12-01

    In France, in 2015, endometrial cancer (CE) is the first gynecological cancer in terms of incidence and the fourth cause of cancer of the woman. About 8151 new cases and nearly 2179 deaths have been reported. Treatments (surgery, external radiotherapy, brachytherapy and chemotherapy) are currently delivered on the basis of an estimation of the recurrence risk, an estimation of lymph node metastasis or an estimate of survival probability. This risk is determined on the basis of prognostic factors (clinical, histological, imaging, biological) taken alone or grouped together in the form of classification systems, which are currently insufficient to account for the evolutionary and prognostic heterogeneity of endometrial cancer. For endometrial cancer, the concept of mathematical modeling and its application to prediction have developed in recent years. These biomathematical tools have opened a new era of care oriented towards the promotion of targeted therapies and personalized treatments. Many predictive models have been published to estimate the risk of recurrence and lymph node metastasis, but a tiny fraction of them is sufficiently relevant and of clinical utility. The optimization tracks are multiple and varied, suggesting the possibility in the near future of a place for these mathematical models. The development of high-throughput genomics is likely to offer a more detailed molecular characterization of the disease and its heterogeneity. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  12. Acylcarnitines profile best predicts survival in horses with atypical myopathy.

    Directory of Open Access Journals (Sweden)

    François Boemer

    Full Text Available Equine atypical myopathy (AM is caused by hypoglycin A intoxication and is characterized by a high fatality rate. Predictive estimation of survival in AM horses is necessary to prevent unnecessary suffering of animals that are unlikely to survive and to focus supportive therapy on horses with a possible favourable prognosis of survival. We hypothesized that outcome may be predicted early in the course of disease based on the assumption that the acylcarnitine profile reflects the derangement of muscle energetics. We developed a statistical model to prognosticate the risk of death of diseased animals and found that estimation of outcome may be drawn from three acylcarnitines (C2, C10:2 and C18 -carnitines with a high sensitivity and specificity. The calculation of the prognosis of survival makes it possible to distinguish the horses that will survive from those that will die despite severe signs of acute rhabdomyolysis in both groups.

  13. Cardiac arrest in the toilet: clinical characteristics and resuscitation profiles.

    Science.gov (United States)

    Inamasu, Joji; Miyatake, Satoru

    2013-03-01

    The great majority of non-traumatic cardiac arrests (CA) occur at home. The toilet is a closed and private room where CA occurs frequently. However, due to the feelings of privacy that are associated with this room, the circumstances and causes of CA in the toilet have rarely been investigated. A retrospective study was conducted to clarify clinical characteristics and resuscitation profiles of patients sustaining CA in the toilet. Among 907 CA patients treated during a 4-year period, 101 (11 %) sustained CA in the toilet. While the collapse was witnessed in only 10 % of these patients, return of spontaneous circulation (ROSC) was achieved in 41 %. However, the long-term survival rate was 1 %. Multivariate regression analysis revealed that a history of cardiac diseases was predictive of CA in the toilet (odds ratio 3.045; 95 % confidence interval 1.756-5.282) but that there was no correlation with advanced age. The frequency of CA in the toilet may be influenced moderately by seasonal/circadian variations. The 101 patients were classified into four subgroups according to mode of discovery of CA. The frequency of ROSC was highest in those who collapsed in the presence of caregivers and lowest in those whose collapse were discovered later by family members being worried that the patient stayed in the toilet "too long." Imaging studies revealed life-threatening extra-cardiac lesions responsible for CA, such as subarachnoid hemorrhage and aortic dissection, in 23 % of the patient cohort. The rarity of long-term survival among individuals sustaining CA in the toilet is mainly due to the delay in discovering the individual who collapsed. Although a history of cardiac diseases is a risk factor, predicting who may sustain CA in the toilet remains difficult due to etiological heterogeneity.

  14. Clinical predictive factors of pathologic tumor response

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chi Hwan; Kim, Won Dong; Lee, Sang Jeon; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2012-09-15

    The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

  15. Clinical profile and complication of malaria hepatopathy.

    Science.gov (United States)

    Fazil, Abul; Vernekar, Pradeep V; Geriani, Disha; Pant, Sadip; Senthilkumaran, Subramanian; Anwar, Naureen; Prabhu, Asha; Menezes, Ritesh G

    2013-10-01

    This study was designed to study the patient characteristics, presenting features and complications of malaria in patients with elevated liver enzymes and to compare these data to those of patients with normal liver enzymes. A convenient sample of 100 patients with malaria was selected from three tertiary care referral hospitals. Study subjects were divided into two groups: (1) patients (controls) with normal liver enzymes and (2) patients (cases) with >3 times the normal liver enzymes in the absence of an alternate explanation for such elevation. Patient characteristics, presenting features and complications of malaria in these two groups were studied. Data were collected using a semi-structured pretested proforma and were analyzed using the statistical analysis program SPSS, version 11.5 (SPSS, Inc., Chicago, IL). The mean ages were 38.12 years for the cases and 35.20 years for the controls with a non-significant p value of 0.289. Males composed 82% of the cases that were diagnosed with malarial hepatopathy; the remaining 18% were females. Falciparum malaria was present in 56% of the cases, compared to 12% of the controls. Icterus was present in 66% of cases of malarial hepatopathy, compared to 32% of the controls. Of the 66% of these cases, 18.18% had serum bilirubin >3mg%, whereas out of the 32% of the controls presenting with icterus, only 5.55% had serum bilirubin >3mg% (p=0.003). Of the cases with malarial hepatopathy, 38% suffered from hypoglycemia, compared to 0% of the controls (pcases presented with thrombocytopenia, compared to 70% of the controls (pcases suffered from renal failure with serum creatinine levels >2mg%, compared to 2% of the controls (p=0.060). Plasmodium falciparum infection (either alone or along with P. vivax) is the leading cause of malarial hepatopathy. Jaundice is a common clinical manifestation among these patients. Patients with malarial hepatopathy have increased incidences of hypoglycemia and thrombocytopenia. Malarial

  16. Constructing Prediction Models from Expression Profiles for Large Scale lncRNA-miRNA Interaction Profiling.

    Science.gov (United States)

    Huang, Yu-An; Chan, Keith C C; You, Zhu-Hong

    2017-10-23

    The interaction of miRNA and lncRNA is known to be important for gene regulations. However, not many computational approaches have been developed to analyse known interactions and predict the unknown ones. Given that there are now more evidences that suggest that lncRNA-miRNA interactions are closely related to their relative expression levels in the form of a titration mechanism, we analyzed the patterns in large-scale expression profiles of known lncRNA-miRNA interactions. From these uncovered patterns, we noticed that lncRNAs tend to interact collaboratively with miRNAs of similar expression profiles, and vice versa. By representing known interaction between lncRNA and miRNA as a bipartite graph, we propose here a technique, called EPLMI, to construct a prediction model from such a graph. EPLMI performs its tasks based on the assumption that lncRNAs that are highly similar to each other tend to have similar interaction or non-interaction patterns with miRNAs and vice versa. The effectiveness of the prediction model so constructed has been evaluated using the latest dataset of lncRNA-miRNA interactions. The results show that the prediction model can achieve AUCs of 0.8522 and 0.8447±0.0017 based on LOOCV and 5-fold cross validation. Using this model, we show that lncRNA-miRNA interactions can be reliably predicted. We also show that we can use it to select the most likely lncRNA targets that specific miRNAs would interact with. We believe that the prediction models discovered by EPLMI can yield great insights for further research on ceRNA regulation network. To the best of our knowledge, EPLMI is the first technique that is developed for large-scale lncRNA-miRNA interaction profiling. Matlab codes and dataset are available at https://github.com/yahuang1991polyu/EPLMI/. yu-an.huang@connect.polyu.hk. Supplementary data are available at Bioinformatics online.

  17. Prediction of Facial Profile Based on Morphometric Measurements and Profile Characteristics of Permanent Maxillary Central Incisor Teeth

    Directory of Open Access Journals (Sweden)

    N Raghavendra

    2015-01-01

    Full Text Available The computation of facial profile from dental morphometrics has been a subject of great interest in forensic odontology. The use of teeth to draw a profile and facial features is valuable in times of mass disasters when body remains are unavailable due to extreme destruction. This study aims to identify and evaluate applicable parameters in the permanent maxillary central incisors and the face of an individual. A correlation of these parameters establishes a mathematical equation that further charts a tooth-facial profile table. Thirty soft and hard tissue landmarks on the face in the frontal and the lateral profiles (using standardized photographs and seven landmarks on the facial/labial surface of the clinical crown of the permanent maxillary central incisor (using casts of the maxilla were identified for the study. Based on these, a set of eight horizontal and seven vertical parameters on the face and four parameters on the tooth were created for the assessment. Internal and external correlations between the two were carried out and statistically analyzed. A logistic regression was made to predict the probability of the parameters most likely to be reproduced in the creation of the facial profile, based on tooth morphometrics. The results indicated a definite correlation between the facial and the tooth parameters. Among the multiple parameters, a definite correlation in the horizontal dimension could be established between the mouth width and the mesiodistal width (MDW of the tooth. In the vertical dimension, a definite relationship existed between the crown height of the tooth and the width of the midface (zygoma-mandible. There exist divergences in the correlation of tooth and facial parameters.

  18. Clinical profile and outcome of pediatrics tetanus: the experience of ...

    African Journals Online (AJOL)

    Background: Tetanus is an acute vaccine preventable illness manifested by neuromuscular dysfunction due to a potent exotoxin, tetanospasmin produced by Clostridium tetani. It is a common health problem in developing countries like Ethiopia. The aim of this study was to assess clinical profile and outcome of Pediatrics ...

  19. Comparison of clinical profiles and treatment outcomes between ...

    African Journals Online (AJOL)

    Other factors found to prolong the time to improvement among all patients were old age, education, being single, unemployment, the diagnoses of schizophrenia, and substance abuse. Conclusion: The clinical profiles and treatment outcomes were poorer among the vagrant mentally ill patients, underscoring a need for ...

  20. Epidemiological, clinical and therapeutic profile of cervical cancer in ...

    African Journals Online (AJOL)

    Background: Cervical cancer is a sexually transmitted cancer caused by oncogenic Human Papilloma Virus (HPV). Aim: The study aimed to determine the epidemiological, clinical and therapeutic profile of cervical cancer in Butembo. Method: This was a retrospective and descriptive study. Case records of patients managed ...

  1. Does the clinical profile of Gujarati patients with Takayasu's ...

    African Journals Online (AJOL)

    Takayasu's aortoarteritis is a well-known yet rare form of large vessel vasculitis. It is a chronic inflammatory diseas, which has remained an enigma since it was first described a century ago. The present study was done to document the demographic profile, clinical course, complications and survival of 30 consecutive ...

  2. Pattern and clinical profile of children with complex cardiac anomaly ...

    African Journals Online (AJOL)

    Pattern and clinical profile of children with complex cardiac anomaly at University of Nigeria Teaching Hospital, Ituku‑Ozalla, Enugu State, Nigeria. ... ventricle) with left sided aorta, hypoplastic tricuspid valve with a PDA (patent ductus artriosus), TOF (tetralogy of fallot), prolapse of aortic valve, and pulmonary regurgitation.

  3. Clinical profile of cyanotic congenital heart disease in neonatal ...

    African Journals Online (AJOL)

    Objective: The aim of this work was to study clinical profile and available therapeutic modalities used in the management of CCHD. Subjects and methods: This was a prospective study carried out for a period of one year, starting from January 2011, and included 50 neonates admitted to neonatal intensive care unit (NICU) ...

  4. Profile of clinically-diagnosed dementias in a neuropsychiatric ...

    African Journals Online (AJOL)

    Objective: Many subjects with dementia present primarily to neuropsychiatric practices because of behavioural and psychological ... institutional care.10. Stemming from the paucity of data on dementia in psychiatry practices across black Africa, we reviewed the profile of clinically-diagnosed dementias seen in a pioneer.

  5. Prediction of propagated wave profiles based on point measurement

    Directory of Open Access Journals (Sweden)

    Lee Sang-Beom

    2014-03-01

    Full Text Available This study presents the prediction of propagated wave profiles using the wave information at a fixed point. The fixed points can be fixed in either space or time. Wave information based on the linear wave theory can be expressed by Fredholm integral equation of the first kinds. The discretized matrix equation is usually an ill-conditioned system. Tikhonov regularization was applied to the ill-conditioned system to overcome instability of the system. The regularization parameter is calculated by using the L-curve method. The numerical results are compared with the expe¬rimental results. The analysis of the numerical computation shows that the Tikhonov regularization method is useful.

  6. Convulsive status epilepticus: clinical profile in a developing country.

    Science.gov (United States)

    Murthy, Jagarlapudi M K; Jayalaxmi, Sita S; Kanikannan, Meena A

    2007-12-01

    In developing countries optimal care of status epilepticus (SE) is associated with major barriers, particularly transportation. A prospective study of SE was performed between 1994 and 1996 to determine the clinical profile, response to treatment and outcome, Glasgow Outcome Scale (GOS). Of the 85 patients admitted, the mean age was 33 years (8-75 years), 16% <16 years of age. The mean duration of SE before admission was 18.02 h (1-72 h). Only 23 (28%) patients, all locals, presented within <3 h of onset. Etiology included acute symptomatic (54%), remote symptomatic (7%), cryptogenic (19%), and established epilepsy (20%). Central nervous system infections accounted for 24 (28%) of the etiologies. Seventy-five (88%) patients responded to first-line drugs and 10 (12%) required second-line drugs. The mean duration of SE was significantly long in nonresponders (Mean +/- SD: 32.6 +/- 20.11 vs. 15.2 +/- 18.32, p < 0.006). Duration (p < 0.01; OR 1.04, 95% CI 1.01-1.07) and acute symptomatic etiology (p < 0.038; OR 10.38, 95% CI 1.13-95.09) were the independent predictors of no-response to first-line drugs. Of the nine deaths (10.5%), eight were in acute symptomatic group. Predictors of mortality included female sex (p < 0.017, OR 13.41, 95% CI 1.59-115.38) and lack of response to first-line drugs (p < 0.0001, OR 230.27, 95% CI 8.78-6037.19). Longer duration was associated with poor GOS 1-4 (p = 0.001). Of the 37 patients with <6 h, 81% had GOC5 outcome. This study suggests that longer duration of SE and acute symptomatic etiology are independent predictors of lack of response to first-line drugs. Failure to respond to first-line drugs and duration predict the outcome.

  7. Guillain-Barré syndrome: clinical profile and management

    Directory of Open Access Journals (Sweden)

    Sudulagunta, Sreenivasa Rao

    2015-09-01

    Full Text Available Introduction: Guillain-Barré syndrome (GBS is a fulminant polyradiculoneuropathy that is acute, frequently severe and autoimmune in nature. Etiology of GBS is incompletely understood, prognosis is usually good with early detection and prompt treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and electrodiagnostic features of patients with GBS and mode of management, complications and prognostic factors.Methods: Data of 1,166 patients admitted with GBS or presented to outpatient department (previous medical records with GBS between January 2003 and January 2014 were analyzed. Results: No difference in genders noted. Around 35% of patients are above 50 years of age. Poor control of diabetes with mean HbA of 8.1 ± 2.11 is found on analysis. Seasonal occurrence in GBS is prominent in winter 484 (41.50% and mechanically ventilated were 449 (38.50% patients. 48 (4.11% deaths were attributed to GBS. Neurological analysis revealed cranial nerve involvement in 407 (34.90% patients, facial palsy in 401 (34.39% and ataxia in 88 (7.54% patients. Most patients in plasma exchange group belonged to the lower socio-economic status. Mean cerebrospinal fluid (CSF protein levels was (n=962 113.8 ± 11.8 mg/dl. Conduction block determined indirectly by absent H-reflex was noted in 891 (90.64% patients. No difference in complications and outcome is found in treatment regimens of intravenous immunoglobulin (IVIG and plasma exchange.Conclusion: Seasonal occurrence predominantly in winter is noted. Peak flow test may be a predictor of assessing requirement of mechanical ventilation and prognosis. Conduction block is the major abnormality noted in electrophysiological studies and proximal nerve segment assessing with Erb’s point stimulation has high predictive value. IVIG treatment is more expensive but is associated with less duration of hospital stay.

  8. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans.

    Science.gov (United States)

    Rhee, Eugene P; Cheng, Susan; Larson, Martin G; Walford, Geoffrey A; Lewis, Gregory D; McCabe, Elizabeth; Yang, Elaine; Farrell, Laurie; Fox, Caroline S; O'Donnell, Christopher J; Carr, Steven A; Vasan, Ramachandran S; Florez, Jose C; Clish, Clary B; Wang, Thomas J; Gerszten, Robert E

    2011-04-01

    Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry-based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment.

  9. Computational analysis of epidermal growth factor receptor mutations predicts differential drug sensitivity profiles towards kinase inhibitors.

    Science.gov (United States)

    Akula, Sravani; Kamasani, Swapna; Sivan, SreeKanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

    2018-01-21

    A significant proportion of lung cancer patients carry mutations in the epidermal growth factor receptor (EGFR) kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain were shown to cause enhanced efficacy of inhibitor treatment in NSCLC patients. Several less frequent ("Uncommon") mutations in the EGFR kinase domain with potential implications in treatment response were also reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity/resistance. A large scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed and drug sensitivity profiles for each mutant towards seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity (RIBA) towards each drug as compared to that of the ATP was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity towards first and next generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations towards multiple inhibitors which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  10. Connecting clinical and actuarial prediction with rule-based methods

    NARCIS (Netherlands)

    Fokkema, M.; Smits, N.; Kelderman, H.; Penninx, B.W.

    2015-01-01

    Meta-analyses comparing the accuracy of clinical versus actuarial prediction have shown actuarial methods to outperform clinical methods, on average. However, actuarial methods are still not widely used in clinical practice, and there has been a call for the development of actuarial prediction

  11. Assist feature printability prediction by 3-D resist profile reconstruction

    Science.gov (United States)

    Zheng, Xin; Huang, Jensheng; Chin, Fook; Kazarian, Aram; Kuo, Chun-Chieh

    2012-06-01

    properties may then be used to optimize the printability vs. efficacy of an SRAF either prior to or during an Optical Proximity Correction (OPC) run. The process models that are used during OPC have never been able to reliably predict which SRAFs will print. This appears to be due to the fact that OPC process models are generally created using data that does not include printed subresolution patterns. An enhancement to compact modeling capability to predict Assist Features (AF) printability is developed and discussed. A hypsometric map representing 3-D resist profile was built by applying a first principle approximation to estimate the "energy loss" from the resist top to bottom. Such a 3-D resist profile is an extrapolation of a well calibrated traditional OPC model without any additional information. Assist features are detected at either top of resist (dark field) or bottom of resist (bright field). Such detection can be done by just extracting top or bottom resist models from our 3-D resist model. There is no measurement of assist features needed when we build AF but it can be included if interested but focusing on resist calibration to account for both exposure dosage and focus change sensitivities. This approach significantly increases resist model's capability for predicting printed SRAF accuracy. And we don't need to calibrate an SRAF model in addition to the OPC model. Without increase in computation time, this compact model can draw assist feature contour with real placement and size at any vertical plane. The result is compared and validated with 3-D rigorous modeling as well as SEM images. Since this method does not change any form of compact modeling, it can be integrated into current MBAF solutions without any additional work.

  12. Predicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma: Utility of Immune Profiling

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    Benjamin W. Teh

    2017-10-01

    Full Text Available BackgroundA translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted.MethodsBaseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 × 106 cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05 and refined with multivariable analysis to define a predictive immune profile.Results525 stimulant samples with 19,950 stimulant–cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection.ConclusionProfiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy.

  13. Clinical and epidemiological profiles of non-traumatic myelopathies

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    Wladimir Bocca Vieira de Rezende Pinto

    2016-02-01

    Full Text Available ABSTRACT Non-traumatic myelopathies represent a heterogeneous group of neurological conditions. Few studies report clinical and epidemiological profiles regarding the experience of referral services. Objective To describe clinical characteristics of a non-traumatic myelopathy cohort. Method Epidemiological, clinical, and radiological variables from 166 charts of patients assisted between 2001 and 2012 were compiled. Results The most prevalent diagnosis was subacute combined degeneration (11.4%, followed by cervical spondylotic myelopathy (9.6%, demyelinating disease (9%, tropical spastic paraparesis (8.4% and hereditary spastic paraparesis (8.4%. Up to 20% of the patients presented non-traumatic myelopathy of undetermined etiology, despite the broad clinical, neuroimaging and laboratorial investigations. Conclusion Regardless an extensive evaluation, many patients with non-traumatic myelopathy of uncertain etiology. Compressive causes and nutritional deficiencies are important etiologies of non-traumatic myelopathies in our population.

  14. Clinical versus statistical prediction: the contribution of Paul E. Meehl.

    Science.gov (United States)

    Grove, William M

    2005-10-01

    The background of Paul E. Meehl's work on clinical versus statistical prediction is reviewed, with detailed analyses of his arguments. Meehl's four main contributions were the following: (a) he put the question, of whether clinical or statistical combinations of psychological data yielded better predictions, at center stage in applied psychology; (b) he convincingly argued, against an array of objections, that clinical versus statistical prediction was a real (not concocted) problem needing thorough study; (c) he meticulously and even-handedly dissected the logic of clinical inference from theoretical and probabilistic standpoints; and (c) he reviewed the studies available in 1954 and thereafter, which tested the validity of clinical versus statistical predictions. His early conclusion that the literature strongly favors statistical prediction has stood up extremely well, and his conceptual analyses of the prediction problem (especially his defense of applying aggregate-based probability statements to individual cases) have not been significantly improved since 1954. 2005 Wiley Periodicals, Inc.

  15. The potential use of expression profiling: implications for predicting treatment response in rheumatoid arthritis.

    Science.gov (United States)

    Smith, Samantha Louise; Plant, Darren; Eyre, Stephen; Barton, Anne

    2013-07-01

    Whole genome expression profiling, or transcriptomics, is a high throughput technology with the potential for major impacts in both clinical settings and drug discovery and diagnostics. In particular, there is much interest in this technique as a mechanism for predicting treatment response. Gene expression profiling entails the quantitative measurement of messenger RNA levels for thousands of genes simultaneously with the inherent possibility of identifying biomarkers of response to a particular therapy or by singling out those at risk of serious adverse events. This technology should contribute to the era of stratified medicine, in which patient specific populations are matched to potentially beneficial drugs via clinical tests. Indeed, in the oncology field, gene expression testing is already recommended to allow rational use of therapies to treat breast cancer. However, there are still many issues surrounding the use of the various testing platforms available and the statistical analysis associated with the interpretation of results generated. This review will discuss the implications this promising technology has in predicting treatment response and outline the various advantages and pitfalls associated with its use.

  16. Clinical Predictive Modeling Development and Deployment through FHIR Web Services

    Science.gov (United States)

    Khalilia, Mohammed; Choi, Myung; Henderson, Amelia; Iyengar, Sneha; Braunstein, Mark; Sun, Jimeng

    2015-01-01

    Clinical predictive modeling involves two challenging tasks: model development and model deployment. In this paper we demonstrate a software architecture for developing and deploying clinical predictive models using web services via the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The services enable model development using electronic health records (EHRs) stored in OMOP CDM databases and model deployment for scoring individual patients through FHIR resources. The MIMIC2 ICU dataset and a synthetic outpatient dataset were transformed into OMOP CDM databases for predictive model development. The resulting predictive models are deployed as FHIR resources, which receive requests of patient information, perform prediction against the deployed predictive model and respond with prediction scores. To assess the practicality of this approach we evaluated the response and prediction time of the FHIR modeling web services. We found the system to be reasonably fast with one second total response time per patient prediction. PMID:26958207

  17. Clinical Predictive Modeling Development and Deployment through FHIR Web Services.

    Science.gov (United States)

    Khalilia, Mohammed; Choi, Myung; Henderson, Amelia; Iyengar, Sneha; Braunstein, Mark; Sun, Jimeng

    2015-01-01

    Clinical predictive modeling involves two challenging tasks: model development and model deployment. In this paper we demonstrate a software architecture for developing and deploying clinical predictive models using web services via the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The services enable model development using electronic health records (EHRs) stored in OMOP CDM databases and model deployment for scoring individual patients through FHIR resources. The MIMIC2 ICU dataset and a synthetic outpatient dataset were transformed into OMOP CDM databases for predictive model development. The resulting predictive models are deployed as FHIR resources, which receive requests of patient information, perform prediction against the deployed predictive model and respond with prediction scores. To assess the practicality of this approach we evaluated the response and prediction time of the FHIR modeling web services. We found the system to be reasonably fast with one second total response time per patient prediction.

  18. Integrated analysis of drug-induced gene expression profiles predicts novel hERG inhibitors.

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    Joseph J Babcock

    Full Text Available Growing evidence suggests that drugs interact with diverse molecular targets mediating both therapeutic and toxic effects. Prediction of these complex interactions from chemical structures alone remains challenging, as compounds with different structures may possess similar toxicity profiles. In contrast, predictions based on systems-level measurements of drug effect may reveal pharmacologic similarities not evident from structure or known therapeutic indications. Here we utilized drug-induced transcriptional responses in the Connectivity Map (CMap to discover such similarities among diverse antagonists of the human ether-à-go-go related (hERG potassium channel, a common target of promiscuous inhibition by small molecules. Analysis of transcriptional profiles generated in three independent cell lines revealed clusters enriched for hERG inhibitors annotated using a database of experimental measurements (hERGcentral and clinical indications. As a validation, we experimentally identified novel hERG inhibitors among the unannotated drugs in these enriched clusters, suggesting transcriptional responses may serve as predictive surrogates of cardiotoxicity complementing existing functional assays.

  19. Health profiles of foreigners attending primary care clinics in Malaysia.

    Science.gov (United States)

    Ab Rahman, Norazida; Sivasampu, Sheamini; Mohamad Noh, Kamaliah; Khoo, Ee Ming

    2016-06-14

    The world population has become more globalised with increasing number of people residing in another country for work or other reasons. Little is known about the health profiles of foreign population in Malaysia. The aim of this study was to provide a detailed description of the health problems presented by foreigners attending primary care clinics in Malaysia. Data were derived from the 2012 National Medical Care Survey (NMCS), a cross sectional survey of primary care encounters from public and private primary care clinics sampled from five regions in Malaysia. Patients with foreign nationality were identified and analysed for demographic profiles, reasons for encounter (RFEs), diagnosis, and provision of care. Foreigners accounted for 7.7 % (10,830) of all patient encounters from NMCS. Most encounters were from private clinics (90.2 %). Median age was 28 years (IQR: 24.0, 34.8) and 69.9 % were male. Most visits to the primary care clinics were for symptom-based complaints (69.5 %), followed by procedures (23.0 %) and follow-up visit (7.4 %). The commonest diagnosis in public clinics was antenatal care (21.8 %), followed by high risk pregnancies (7.5 %) and upper respiratory tract infection (URTI) (6.8 %). Private clinics had more cases for general medical examination (13.5 %), URTI (13.1 %) and fever (3.9 %). Medications were prescribed to 76.5 % of these encounters. More foreigners were seeking primary medical care from private clinics and the encounters were for general medical examinations and acute minor ailments. Those who sought care from public clinics were for obstetric problems and chronic diseases. Medications were prescribed to two-thirds of the encounters while other interventions: laboratory investigations, medical procedures and follow-up appointment had lower rates in private clinics. Foreigners are generally of young working group and are expected to have mandatory medical checks. The preponderance of obstetrics seen in public

  20. Individual Assessment of Arteriosclerosis by Empiric Clinical Profiling

    Science.gov (United States)

    Mutschelknauss, Marcus; Kummer, Marco; Muser, Juergen; Feinstein, Steve B.; Meyer, Peter M.; Biedermann, Barbara C.

    2007-01-01

    Background Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient. Methodology/Principal Findings 269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient's disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from

  1. Prediction of transposable element derived enhancers using chromatin modification profiles.

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    Ahsan Huda

    Full Text Available Experimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element (TE sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the ENCODE project in two human hematopoietic cell types, GM12878 and K562. We predicted the locations of 2,107 and 1,448 TE-derived enhancers in the GM12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5% of the TE-derived enhancers are shared between the two. We evaluated the functional effect of TE-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of TE-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of TE-derived enhancers in their vicinity. As such, genes that are up-regulated in the GM12878 cell line and down-regulated in K562 have significantly more TE-derived enhancers in their vicinity in the GM12878 cell line and vice versa. These data indicate that human TE-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of TE-derived sequences is mediated by epigenetic regulatory mechanisms.

  2. A profile of patients attending sports medicine clinics.

    Science.gov (United States)

    Finch, C F; Kenihan, M A

    2001-08-01

    To describe the sociodemographic profile of sports injury patients who attend sports medicine clinics for treatment and to describe their reasons for choosing to attend such clinics. Data were collected as part of a fully audited injury surveillance system implemented within sports medicine clinics. The study was conducted within five allied multidisciplinary sports medicine clinics in metropolitan Melbourne, Australia. All patients initially presenting for treatment of a new sports or active recreation injury over the period August 1997 to August 1998 were eligible for this study, irrespective of the practitioner providing the treatment. Data were obtained on 6476 patients. The median age of the patients was 25.4 years (range 6.8--81.6) and most were male (69.8% of cases; 95% confidence interval (95% CI) 68.7 to 70.9). Patients had both professional and non-professional backgrounds and were not just local suburb residents. Many patients had insurance cover for their injury treatment: 59.0% (95% CI 58.6 to 59.4) had some private health insurance and 46.6% (95% CI 45.4 to 47.8) had club/association insurance. The most common reasons for attending a clinic was its location (36.8%; 95% CI 36.5 to 37.1) and referral/recommendation (31.0%; 95% CI 30.7 to 31.3). Sports medicine clinics provide treatment for a broad spectrum of injured sports participants across a variety of sporting/recreation contexts. Although these clinics mainly serve the immediate geographic community, the sports speciality and expertise of a particular clinic can attract patients from further afield. This information can help sports medicine clinics to market their services more efficiently to meet the needs of their potential patients.

  3. Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

    Science.gov (United States)

    Zhang, Wenqian; Yu, Ying; Hertwig, Falk; Thierry-Mieg, Jean; Zhang, Wenwei; Thierry-Mieg, Danielle; Wang, Jian; Furlanello, Cesare; Devanarayan, Viswanath; Cheng, Jie; Deng, Youping; Hero, Barbara; Hong, Huixiao; Jia, Meiwen; Li, Li; Lin, Simon M; Nikolsky, Yuri; Oberthuer, André; Qing, Tao; Su, Zhenqiang; Volland, Ruth; Wang, Charles; Wang, May D; Ai, Junmei; Albanese, Davide; Asgharzadeh, Shahab; Avigad, Smadar; Bao, Wenjun; Bessarabova, Marina; Brilliant, Murray H; Brors, Benedikt; Chierici, Marco; Chu, Tzu-Ming; Zhang, Jibin; Grundy, Richard G; He, Min Max; Hebbring, Scott; Kaufman, Howard L; Lababidi, Samir; Lancashire, Lee J; Li, Yan; Lu, Xin X; Luo, Heng; Ma, Xiwen; Ning, Baitang; Noguera, Rosa; Peifer, Martin; Phan, John H; Roels, Frederik; Rosswog, Carolina; Shao, Susan; Shen, Jie; Theissen, Jessica; Tonini, Gian Paolo; Vandesompele, Jo; Wu, Po-Yen; Xiao, Wenzhong; Xu, Joshua; Xu, Weihong; Xuan, Jiekun; Yang, Yong; Ye, Zhan; Dong, Zirui; Zhang, Ke K; Yin, Ye; Zhao, Chen; Zheng, Yuanting; Wolfinger, Russell D; Shi, Tieliu; Malkas, Linda H; Berthold, Frank; Wang, Jun; Tong, Weida; Shi, Leming; Peng, Zhiyu; Fischer, Matthias

    2015-06-25

    Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

  4. Externalising and emotional categories, diagnostic groups and clinical profiles

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    Bower Alison

    2010-07-01

    Full Text Available Abstract Background It has been proposed that gains would be made in the validity of the psychiatric classification system if many of the present 'neurotic' or personality disorders were subsumed into two over-arching groups, externalising and emotional disorders. If diagnostic sub-categories from the first digit coding structures within ICD-10 do, in fact, share clinical phenomenology that align with the major externalising/emotional distinction, this further supports the proposal and contributes to face validity. The aim of the study was to examine the distribution of particular psychopathology within and between two proposed over-arching groupings - externalising and emotional disorders - in a clinical sample. Method The distributions of HoNOS derived information in relation to the proposed clusters of emotional disorders and extrinsic disorders are examined. Results Statistically significant differences in profiles between the emotional and the externalising groupings are consistent with the proposed classification development. The HoNOS (Health of Nation Outcome Scale measures of self harm, depression, aggression, occupational/leisure problems and drug and alcohol consumption are the five most significant discriminators between the two groups. Discussion The details of the profile differences within the two over arching groups suggest that further examination is required. Useful work could include examination in credibly large and unselected patient populations of the factor structure demonstrated in non patient samples. Prospective comprehensive trials of the contributions the proposed classification could make to clinical decision making would also help illuminate this area.

  5. A Clinical Profile of Hepatitis A Patients in Jakarta, Indonesia

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    Randy Adiwinata

    2017-04-01

    Full Text Available Background: To determine the incidence of hepatitis A infections and the clinical profiles of adult patients admitted to public hospitals in Jakarta, Indonesia. Methods: This was a cross-sectional study that utilised consecutive secondary data from internal medicine wards of seven public hospitals in Jakarta between 2011 and 2013. Eligibility criteria included patients over the age of 18 years and an ICD-10 diagnosis code of B15, acute hepatitis A. Case proportion was reported per 1000 people by dividing incidence per year to total in-ward patients. Clinical profiles were reported descriptively. Laboratory results were compared and categorised into groups of patients aged below and above 25 years old. Results: Data revealed that hospitalisations of patients with hepatitis A had decreased from 2011 to 2013. 289 patients were studied, the majority were young adults (18-25 years old and their common chief complaints were nausea (36%, fever (24%, and jaundice (21%. Higher bilirubin levels were seen in older patients. There were 13 patients coinfected with hepatitis B, one patient coinfected with hepatitis C, and one patient coinfected with HIV. Conclusions: The proportion of hepatitis A infection amongst adults admitted to public hospitals in Jakarta was low and had decreased during the study period. Most of the patients reported classical clinical manifestations. This study found that the targeted age group may benefit from receiving routine hepatitis A vaccinations.

  6. Clinical and nutritional profile of individuals with chagas disease

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    Juliana Geraix

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanossoma cruzi, affects approximately 18 million individuals in the Americas, 5 million of which live in Brazil. Most chronic sufferers have either the indeterminate form of the disease, without organic compromise, or the cardiac or digestive forms. Despite the importance of this disease, there is no information on the effect of nutrition on CD evolution. We evaluated the clinical-nutritional profile of individuals with CD treated at the Tropical Diseases Nutrition Out-Patient Clinic of the Botucatu School of Medicine, UNESP. A retrospective cohort study was performed between 2002 and 2006, on 66 patients with serum and parasitological diagnosis of CD. Epidemiological, clinical, nutritional, and biochemical data were collected, including gender, age, skin color, smoking, alcoholism, physical activity, weight, stature, body mass index, abdominal circumference, glycemia, and lipid profile. Fifty-three percent were male and 47% female; 96% were white skinned. Mean age was 49.6±6.36 years. The predominant form was indeterminate in 71%; smoking and drinking were recorded in 23% and 17%, respectively. Sedentariness predominated in 83%, and 55% presented increased abdominal circumference. Most, 94%, were overweight or obese. The biochemical exams revealed hyperglycemia in 12% and dyslipidemia in 74%. These findings suggest that the Chagas population presents co-morbidities and risk factors for developing chronic non-transmissible diseases, including cardiovascular diseases, making CD evolution even worse.

  7. Clinical and nutritional profile of individuals with Chagas disease.

    Science.gov (United States)

    Geraix, Juliana; Ardisson, Lidiane Paula; Marcondes-Machado, Jussara; Pereira, Paulo Câmara Marques

    2007-08-01

    Chagas disease (CD), caused by the protozoan Trypanossoma cruzi, affects approximately 18 million individuals in the Americas, 5 million of which live in Brazil. Most chronic sufferers have either the indeterminate form of the disease, without organic compromise, or the cardiac or digestive forms. Despite the importance of this disease, there is no information on the effect of nutrition on CD evolution. We evaluated the clinical-nutritional profile of individuals with CD treated at the Tropical Diseases Nutrition Out-Patient Clinic of the Botucatu School of Medicine, UNESP. A retrospective cohort study was performed between 2002 and 2006, on 66 patients with serum and parasitological diagnosis of CD. Epidemiological, clinical, nutritional, and biochemical data were collected, including gender, age, skin color, smoking, alcoholism, physical activity, weight, stature, body mass index, abdominal circumference, glycemia, and lipid profile. Fifty-three percent were male and 47% female; 96% were white skinned. Mean age was 49.6 +/- 6.36 years. The predominant form was indeterminate in 71%; smoking and drinking were recorded in 23% and 17%, respectively. Sedentariness predominated in 83%, and 55% presented increased abdominal circumference. Most, 94%, were overweight or obese. The biochemical exams revealed hyperglycemia in 12% and dyslipidemia in 74%. These findings suggest that the Chagas population presents co-morbidities and risk factors for developing chronic non-transmissible diseases, including cardiovascular diseases, making CD evolution even worse.

  8. Antimicrobial sensitivity profile of Staphylococcus spp. Isolated from clinical mastitis

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    Thamires Martins

    2012-12-01

    Full Text Available Inflammation of the mammary gland, which is also known as mastitis, occupies a prominent place among the diseases that affect dairy cattle, having a great economic importance in the dairy sector. Mastitis may have different origins, however, infectious mastitis is the most frequent and represents a risk to public health due to the propagation of microorganisms through milk. Staphylococcus spp. are considered the microorganisms that cause the greatest losses in milk production, being that Staphylococcus aureus is the pathogen of major importance because they present high resistence to antimicrobials. Empirical treatment, without prior identification of the pathogens and their resistance profile, may contribute to the emergence of multidrug-resistant strains and risk the efficiency of the antimicrobial. In that scenery, the study aimed to evaluate the resistance profile of Staphylococcus spp. against some antimicrobials used in the treatment of cows with clinical mastitis. The study was conducted on a property in the state of São Paulo from January 2011 to June 2012. We evaluated 29 lactating cows that present clinical mastitis in, at least, one mammary quarter. The diagnosis of clinical mastitis was performed by evaluating the clinical signs and also by Tamis test. Samples of milk from mammary quarters were collected aseptically in sterile tubes for microbiological evaluation. Microorganisms were isolated on sheep blood agar 5% and Sabouraud agar with chloramphenicol. The sensitivity profile of Staphylococcus spp. to the antibiotics ampicillin, cephalexin, ceftiofur, cefaclor, gentamicin, kanamycin, neomycin, penicillin G and oxacillin, was tested by disk diffusion test on Mueller-Hinton agar. From a total of 106 samples of milk analyzed, 64 (60.38% presented microbiological growth, being observed isolation of Streptococcus spp. 29 (34.52%, Staphylococcus spp. 28 (33.33%, Corynebacterium spp. 17 (20.24%, filamentous fungi 4 (4.76%, yeast 4 (4

  9. Cytokine profiles at birth predict malaria severity during infancy.

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    Edward Kabyemela

    Full Text Available BACKGROUND: Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood. METHODS AND FINDINGS: Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10 were measured at birth (cord blood; N=783 and during subsequent routine follow-up visits (peripheral blood for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear and clinical assessments every 2-4 weeks, and at the time of any illness. Cord blood levels of all cytokines were positively correlated with each other (Spearman's rank correlation. Cord levels of IL-1β and TNF-α (but not other cytokines correlated with levels of the same cytokine measured at routine visits during early life (P < 0.05. Higher cord levels of IL-1β but not TNF-α were associated with lower parasite densities during infancy (P=0.003; Generalized Estimating Equation (GEE method, with an average ~40% reduction versus children with low cord IL-1β levels, and with decreased risk of severe malaria during follow-up (Cox regression: adjusted hazard ratio (95% CI 0.60 (0.39-0.92, P = 0.02. CONCLUSION: IL-1β levels at birth are related to future IL-1β levels as well as the risk of severe malaria in early life. The effect on severe malaria risk may be due in part to the effect of inflammatory cytokines to control parasite density.

  10. Study Of Clinical Profile of Allergic Contact Dermatitis In Pune

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    Sayal S K

    1999-01-01

    Full Text Available One hundred and twenty five cases of clinically diagnosed allergic contact dermatitis were studied. All patients were subjected to patch test with standard test allergens and also with suspected test allergens based on history and clinical profile. Allergic contact dermatitis due to Parthenium hysterophorus was commonest and found in 64% cases, followed by wearing apparel and jewellery in 16.8%, topical medicaments in 8% and cosmetics and occupational contactants in 5.6% cases each. The common individual allergens other than parthenium, were nickel in 8.8%, leather, hair dye and cement in 3.2% each, nitrofurazone and petrol, oil, lubricant (POL in 2.4% each. Patch test with suspected allergens was positive in 72% of cases.

  11. Flexible recalibration of binary clinical prediction models.

    Science.gov (United States)

    Dalton, Jarrod E

    2013-01-30

    Calibration in binary prediction models, that is, the agreement between model predictions and observed outcomes, is an important aspect of assessing the models' utility for characterizing risk in future data. A popular technique for assessing model calibration first proposed by D. R. Cox in 1958 involves fitting a logistic model incorporating an intercept and a slope coefficient for the logit of the estimated probability of the outcome; good calibration is evident if these parameters do not appreciably differ from 0 and 1, respectively. However, in practice, the form of miscalibration may sometimes be more complicated. In this article, we expand the Cox calibration model to allow for more general parameterizations and derive a relative measure of miscalibration between two competing models from this more flexible model. We present an example implementation using data from the US Agency for Healthcare Research and Quality. Copyright © 2012 John Wiley & Sons, Ltd.

  12. The metabolic syndrome in a memory clinic population: Relation with clinical profile and prognosis

    NARCIS (Netherlands)

    Exalto, L.G.; van der Flier, W.M.; van Boheemen, C.J.M.; Kappelle, L.J.; Vrenken, H.; Teunissen, C.; Koene, T.; Scheltens, P.; Biessels, G.J.

    2015-01-01

    Background The metabolic syndrome (MetS) refers to a cluster of cardiovascular risk factors that is associated with an increased risk of cognitive impairment and dementia. It is unclear however, if the presence of the MetS is associated with a particular clinical profile or a different prognosis in

  13. Connectomic profile and clinical phenotype in newly diagnosed glioma patients

    Directory of Open Access Journals (Sweden)

    Jolanda Derks

    2017-01-01

    Full Text Available Gliomas are primary brain tumors, originating from the glial cells in the brain. In contrast to the more traditional view of glioma as a localized disease, it is becoming clear that global brain functioning is impacted, even with respect to functional communication between brain regions remote from the tumor itself. However, a thorough investigation of glioma-related functional connectomic profiles is lacking. Therefore, we constructed functional brain networks using functional MR scans of 71 glioma patients and 19 matched healthy controls using the automated anatomical labelling (AAL atlas and interregional Pearson correlation coefficients. The frequency distributions across connectivity values were calculated to depict overall connectomic profiles and quantitative features of these distributions (full-width half maximum (FWHM, peak position, peak height were calculated. Next, we investigated the spatial distribution of the connectomic profile. We defined hub locations based on the literature and determined connectivity (1 between hubs, (2 between hubs and non-hubs, and (3 between non-hubs. Results show that patients had broader and flatter connectivity distributions compared to controls. Spatially, glioma patients particularly showed increased connectivity between non-hubs and hubs. Furthermore, connectivity distributions and hub-non-hub connectivity differed within the patient group according to tumor grade, while relating to Karnofsky performance status and progression-free survival. In conclusion, newly diagnosed glioma patients have globally altered functional connectomic profiles, which mainly affect hub connectivity and relate to clinical phenotypes. These findings underscore the promise of using connectomics as a future biomarker in this patient population.

  14. Clinical profile of children with developmental delay and microcephaly

    Directory of Open Access Journals (Sweden)

    Anju Aggarwal

    2013-01-01

    Full Text Available Aim: To study the profile of children with developmental delay and microcephaly. Materials and Methods: Children attending child development clinic with developmental delay were evaluated as per protocol. Z scores of head circumference were calculated using WHO charts. Clinical, radiological and etiological profile of those with microcephaly and those without was compared. Results: Of the 414 children with developmental delay 231 had microcephaly (z score ≤ -3. Mean age of children with microcephaly was 35.1 ± 27.9 months (range 4-184, males (72.7%. Comorbidities were epilepsy (42.9%, visual abnormality (26.4%, hearing abnormality (16.9%. Mean DQ was 29.75 + 17.8 in those with microcephaly was significantly lower compared to the rest (P = 0.002. Secondary microcephaly was associated with cerebral palsy in 69.7%. Other causes were congenital infections (4, inborn error of metabolism (3, post-meningoencephalitis (5, malformations (12, and syndromic (13. Neuroimaging was done in 118 (51.1% cases of which 104 (88.1% were abnormal. On comparison children with microcephaly had more epilepsy, lower developmental quotient, vision abnormalities findings as compared to normocephalic children with developmental delay (P > 0.05. Conclusion: Microcephaly was associated with lower, DQ, higher comorbidities in children with developmental delay. Spastic CP is commonly associated with microcephaly.

  15. Clinical abdominal palpation for predicting oligohydramnios in ...

    African Journals Online (AJOL)

    the inclusion criterion, as it is women with suspected prolonged pregnancy who require clinical assessment at the time of referral, including AFV estimation. Exclusion criteria were age <18 years. (because of legal restrictions on informed consent in minors in. South Africa) and previous caesarean section. Participants were.

  16. A clinical prediction rule for histological chorioamnionitis in preterm newborns.

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    Jasper V Been

    Full Text Available BACKGROUND: Histological chorioamnionitis (HC is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns. AIM: Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF in preterm newborns. METHODS: Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤ 32.0 weeks born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216 or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206. HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth. RESULTS: HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92-0.98, a positive predictive value of 80% (95%CI = 74-84%, and a negative predictive value of 93% (95%CI = 88-96%. Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88-0.96, positive predictive value 59% (95%CI = 52-62%, and negative predictive value 97% (95%CI = 93-99%. External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values. CONCLUSION: Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation.

  17. Global proteomics profiling improves drug sensitivity prediction: results from a multi-omics, pan-cancer modeling approach.

    Science.gov (United States)

    Ali, Mehreen; Khan, Suleiman A; Wennerberg, Krister; Aittokallio, Tero

    2017-11-27

    Proteomics profiling is increasingly being used for molecular stratification of cancer patients and cell-line panels. However, systematic assessment of the predictive power of large-scale proteomic technologies across various drug classes and cancer types is currently lacking. To that end, we carried out the first pan-cancer, multi-omics comparative analysis of the relative performance of two proteomic technologies, targeted reverse phase protein array (RPPA) and global mass spectrometry (MS), in terms of their accuracy for predicting the sensitivity of cancer cells to both cytotoxic chemotherapeutics and molecularly-targeted anticancer compounds. Our results in two cell-line panels demonstrate how MS profiling improves drug response predictions beyond that of the RPPA or the other omics profiles when used alone. However, frequent missing MS data values complicate its use in predictive modeling and required additional filtering, such as focusing on completely-measured or known oncoproteins, to obtain maximal predictive performance. Rather strikingly, the two proteomics profiles provided complementary predictive signal both for the cytotoxic and targeted compounds. Further, information about the cellular-abundance of primary target proteins was found critical for predicting the response of targeted compounds, although the non-target features also contributed significantly to the predictive power. The clinical relevance of the selected protein markers was confirmed in cancer patient data. These results provide novel insights into the relative performance and optimal use of the widely-applied proteomic technologies, MS and RPPA, which should prove useful in translational applications, such as defining the best combination of omics technologies and marker panels for understanding and predicting drug sensitivities in cancer patients. Processed datasets, R as well as Matlab implementations of the methods are available at https://github.com/mehr-een/bemkl-rbps. mehreen

  18. Clinical profile of leprosy patients: A prospective study

    Directory of Open Access Journals (Sweden)

    Sejal Thakkar

    2014-01-01

    Full Text Available Introduction: Early diagnosis and early adequate drug treatment is very important aspect to reduce the load in cases of leprosy. So, correct labeling of paucibacillary and multibacillary cases is a prerequisite for the adequate treatment. Confirmation of diagnosis is an important indication for histopathological examination in doubtful cases. Objectives: The present study was carried out to know the clinical profile of leprosy patients, concordance between clinical and histopathological diagnosis in cases of leprosy, and to assess the therapeutic efficacy of antileprosy therapy. Study Design: Two hundred and fifty clinically diagnosed leprosy patients attending skin outdoor patient department (OPD were included in the study. Slit skin smear was performed in all the cases. In that case concordance between clinical and histology can be determined only in 30 cases. All the patients were treated with MDT (multidrug therapy as per WHO guideline. Results: A total of 250 patients attended the clinic with male to female ratio of 1.7:1. The highest incidence was noted in 17-40 years of age group. In the clinical disease spectrum, 40% patients were in the borderline spectrum followed by tuberculoid leprosy (TT (29.2%, lepromatous leprosy (LL (26.8%, and 3.9% of indeterminate leprosy (IL. A total of 18% of patients were of primary neuritic leprosy. A total of 8.3% patients had definite history of contact in the family or neighborhood. Clinicopathological correlation was noted in 60% of patients with maximum disparity (52.9% in the borderline group of patients. A total of 52.8% were MB (Multibacillary and 47.2% were PB (Paucibacillary cases. Morphological index became negative after 6 months in all patients. Mean fall of bacteriological index after 6 months was 0.19, while after 1 year, it was 1.05. Conclusion: Timely diagnosis and adequate treatment of cases with MDT is most effective. Histopathological examination is must in doubtful cases of leprosy.

  19. Three-level prediction of protein function by combining profile-sequence search, profile-profile search, and domain co-occurrence networks.

    Science.gov (United States)

    Wang, Zheng; Cao, Renzhi; Cheng, Jianlin

    2013-01-01

    Predicting protein function from sequence is useful for biochemical experiment design, mutagenesis analysis, protein engineering, protein design, biological pathway analysis, drug design, disease diagnosis, and genome annotation as a vast number of protein sequences with unknown function are routinely being generated by DNA, RNA and protein sequencing in the genomic era. However, despite significant progresses in the last several years, the accuracy of protein function prediction still needs to be improved in order to be used effectively in practice, particularly when little or no homology exists between a target protein and proteins with annotated function. Here, we developed a method that integrated profile-sequence alignment, profile-profile alignment, and Domain Co-Occurrence Networks (DCN) to predict protein function at different levels of complexity, ranging from obvious homology, to remote homology, to no homology. We tested the method blindingly in the 2011 Critical Assessment of Function Annotation (CAFA). Our experiments demonstrated that our three-level prediction method effectively increased the recall of function prediction while maintaining a reasonable precision. Particularly, our method can predict function terms defined by the Gene Ontology more accurately than three standard baseline methods in most situations, handle multi-domain proteins naturally, and make ab initio function prediction when no homology exists. These results show that our approach can combine complementary strengths of most widely used BLAST-based function prediction methods, rarely used in function prediction but more sensitive profile-profile comparison-based homology detection methods, and non-homology-based domain co-occurrence networks, to effectively extend the power of function prediction from high homology, to low homology, to no homology (ab initio cases).

  20. Profiles of verbal working memory growth predict speech and language development in children with cochlear implants.

    Science.gov (United States)

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

    2013-06-01

    Verbal short-term memory (STM) and working memory (WM) skills predict speech and language outcomes in children with cochlear implants (CIs) even after conventional demographic, device, and medical factors are taken into account. However, prior research has focused on single end point outcomes as opposed to the longitudinal process of development of verbal STM/WM and speech-language skills. In this study, the authors investigated relations between profiles of verbal STM/WM development and speech-language development over time. Profiles of verbal STM/WM development were identified through the use of group-based trajectory analysis of repeated digit span measures over at least a 2-year time period in a sample of 66 children (ages 6-16 years) with CIs. Subjects also completed repeated assessments of speech and language skills during the same time period. Clusters representing different patterns of development of verbal STM (digit span forward scores) were related to the growth rate of vocabulary and language comprehension skills over time. Clusters representing different patterns of development of verbal WM (digit span backward scores) were related to the growth rate of vocabulary and spoken word recognition skills over time. Different patterns of development of verbal STM/WM capacity predict the dynamic process of development of speech and language skills in this clinical population.

  1. CDK4 phosphorylation status and a linked gene expression profile predict sensitivity to palbociclib.

    Science.gov (United States)

    Raspé, Eric; Coulonval, Katia; Pita, Jaime M; Paternot, Sabine; Rothé, Françoise; Twyffels, Laure; Brohée, Sylvain; Craciun, Ligia; Larsimont, Denis; Kruys, Véronique; Sandras, Flavienne; Salmon, Isabelle; Van Laere, Steven; Piccart, Martine; Ignatiadis, Michail; Sotiriou, Christos; Roger, Pierre P

    2017-08-01

    Cyclin D-CDK4/6 are the first CDK complexes to be activated in the G1 phase in response to oncogenic pathways. The specific CDK4/6 inhibitor PD0332991 (palbociclib) was recently approved by the FDA and EMA for treatment of advanced ER-positive breast tumors. Unfortunately, no reliable predictive tools are available for identifying potentially responsive or insensitive tumors. We had shown that the activating T172 phosphorylation of CDK4 is the central rate-limiting event that initiates the cell cycle decision and signals the presence of active CDK4. Here, we report that the profile of post-translational modification including T172 phosphorylation of CDK4 differs among breast tumors and associates with their subtypes and risk. A gene expression signature faithfully predicted CDK4 modification profiles in tumors and cell lines. Moreover, in breast cancer cell lines, the CDK4 T172 phosphorylation best correlated with sensitivity to PD0332991. This gene expression signature identifies tumors that are unlikely to respond to CDK4/6 inhibitors and could help to select a subset of patients with HER2-positive and basal-like tumors for clinical studies on this class of drugs. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  2. Clinical profile of patients with adult-onset eosinophilic asthma

    Directory of Open Access Journals (Sweden)

    Jantina C. de Groot

    2016-05-01

    Full Text Available Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age asthma and high blood eosinophil counts (≥0.3×109 L−1 were compared with 361 adult-onset asthma patients with low (<0.3×109 L−1 blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7–8.1, 3.0 (95% CI 1.1–8.1 and 2.4 (95% CI 1.3–4.4, respectively. Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice.

  3. Clinically available RNA profiling tests of prostate tumors: utility and comparison

    Directory of Open Access Journals (Sweden)

    Rong Na

    2016-01-01

    Full Text Available In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer (PCa to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses (e.g., progression and mortality differ even among individuals with similar clinical and pathological characteristics. Existing risk classifiers (TMN grading system, Gleason score, etc. are not accurately enough to represent the biological features of PCa. Using new genomic technologies, novel biomarkers and classifiers have been developed and shown to add value to clinical or pathological risk factors for predicting aggressive disease. Among them, RNA testing (gene expression analysis is useful because it can not only reflect genetic variations but also reflect epigenetic regulations. Commercially available RNA profiling tests (Oncotype Dx, Prolaris, and Decipher have demonstrated strong abilities to discriminate PCa with poor prognosis from less aggressive diseases. For instance, these RNA profiling tests can predict disease progression in active surveillance patients or early recurrence after radical treatments. These tests may offer more dependable methods for PCa prognosis prediction to make more accurate and personal medical decisions.

  4. Do Clinical Symptoms and Signs Predict Reduced Renal Function ...

    African Journals Online (AJOL)

    , Wardha, 1Medicine, All India Institute of Medical Sciences Bhopal, 2Medical Student, Mahatma Gandhi Institute ... Subjects and Methods: We performed a cross‑sectional clinical prediction study and included all consecutive patients admitted ...

  5. Prediction of outcome after subarachnoid hemorrhage : Timing of clinical assessment

    NARCIS (Netherlands)

    van Donkelaar, Carlina E.; Bakker, Nicolaas A.; Veeger, Nic J. G. M.; Uyttenboogaart, Maarten; Metzemaekers, Jan D. M.; Eshghi, Omid S.; Mazuri, Aryan; Foumani, Mahrouz; Luijckx, Gert-Jan; Groen, Rob J. M.; van Dijk, J. Marc C.

    OBJECTIVE Currently, early prediction of outcome after spontaneous subarachnoid hemorrhage (SAH) lacks accuracy despite multiple studies addressing this issue. The clinical condition of the patient on admission as assessed using the World Federation of Neurosurgical Societies (WFNS) grading scale is

  6. Psoriasis prediction from genome-wide SNP profiles

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    Fang Xiangzhong

    2011-01-01

    Full Text Available Abstract Background With the availability of large-scale genome-wide association study (GWAS data, choosing an optimal set of SNPs for disease susceptibility prediction is a challenging task. This study aimed to use single nucleotide polymorphisms (SNPs to predict psoriasis from searching GWAS data. Methods Totally we had 2,798 samples and 451,724 SNPs. Process for searching a set of SNPs to predict susceptibility for psoriasis consisted of two steps. The first one was to search top 1,000 SNPs with high accuracy for prediction of psoriasis from GWAS dataset. The second one was to search for an optimal SNP subset for predicting psoriasis. The sequential information bottleneck (sIB method was compared with classical linear discriminant analysis(LDA for classification performance. Results The best test harmonic mean of sensitivity and specificity for predicting psoriasis by sIB was 0.674(95% CI: 0.650-0.698, while only 0.520(95% CI: 0.472-0.524 was reported for predicting disease by LDA. Our results indicate that the new classifier sIB performs better than LDA in the study. Conclusions The fact that a small set of SNPs can predict disease status with average accuracy of 68% makes it possible to use SNP data for psoriasis prediction.

  7. Association Between Clinical and Microbiologic Cluster Profiles and Peri-implantitis.

    Science.gov (United States)

    Canullo, Luigi; Peñarrocha, Miguel; Monje, Alberto; Catena, Andres; Wang, Hom-Lay; Peñarrocha, David

    The correlation between associated local factors and peri-implantitis remains unknown. The aim of this study was to investigate the association between the clinical and microbiologic profiles and peri-implantitis to eventually categorize different groups of this disease. Subjects with at least one implant presenting signs of peri-implantitis were selected. The clinical, radiographic, occlusal, and microbiologic profiles of these infected implants were collected. Cases were classified into five peri-implantitis groups according to potential disease-triggering factors: surgically, prosthetically, biomechanically, purely plaque-associated, and a combination of them. Generalized estimating equations models were used to study differences among the potential risk factors. Cluster analyses were applied to investigate the correlation between clinical and microbiologic profiles and diseased implant samples. Overall, 110 diseased and 121 healthy implants were included. The biomechanically associated group showed higher levels of microbiologic contamination inside the connection; however, the plaque-associated group had a higher level of microbial variety in the peri-implant sulcus. Cluster analyses demonstrated a significant ability to predict the associated factor of peri-implantitis. Moreover, radiographic marginal bone loss and implant width demonstrated the largest influence on the model. While peri-implantitis represents a plaque-induced inflammatory condition, certain local factors might be associated with this biologic complication, as they imply plaque retention. Therefore, disease classification could be further implemented with the associated surgical, prosthetic, and biomechanical factors to better target the etiology.

  8. Predictive data mining in clinical medicine: current issues and guidelines.

    Science.gov (United States)

    Bellazzi, Riccardo; Zupan, Blaz

    2008-02-01

    The widespread availability of new computational methods and tools for data analysis and predictive modeling requires medical informatics researchers and practitioners to systematically select the most appropriate strategy to cope with clinical prediction problems. In particular, the collection of methods known as 'data mining' offers methodological and technical solutions to deal with the analysis of medical data and construction of prediction models. A large variety of these methods requires general and simple guidelines that may help practitioners in the appropriate selection of data mining tools, construction and validation of predictive models, along with the dissemination of predictive models within clinical environments. The goal of this review is to discuss the extent and role of the research area of predictive data mining and to propose a framework to cope with the problems of constructing, assessing and exploiting data mining models in clinical medicine. We review the recent relevant work published in the area of predictive data mining in clinical medicine, highlighting critical issues and summarizing the approaches in a set of learned lessons. The paper provides a comprehensive review of the state of the art of predictive data mining in clinical medicine and gives guidelines to carry out data mining studies in this field. Predictive data mining is becoming an essential instrument for researchers and clinical practitioners in medicine. Understanding the main issues underlying these methods and the application of agreed and standardized procedures is mandatory for their deployment and the dissemination of results. Thanks to the integration of molecular and clinical data taking place within genomic medicine, the area has recently not only gained a fresh impulse but also a new set of complex problems it needs to address.

  9. Glycogen storage disease type I: clinical and laboratory profile

    Directory of Open Access Journals (Sweden)

    Berenice L. Santos

    2014-12-01

    Full Text Available OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

  10. Behavioral profiles of clinically referred children with intellectual giftedness.

    Science.gov (United States)

    Guénolé, Fabian; Louis, Jacqueline; Creveuil, Christian; Baleyte, Jean-Marc; Montlahuc, Claire; Fourneret, Pierre; Revol, Olivier

    2013-01-01

    It is common that intellectually gifted children--that is, children with an IQ ≥ 130--are referred to paediatric or child neuropsychiatry clinics for socio-emotional problems and/or school underachievement or maladjustment. These clinically-referred children with intellectual giftedness are thought to typically display internalizing problems (i.e., self-focused problems reflecting overcontrol of emotion and behavior), and to be more behaviorally impaired when "highly" gifted (IQ ≥ 145) or displaying developmental asynchrony (i.e., a heterogeneous developmental pattern, reflected in a significant verbal-performance discrepancy on IQ tests). We tested all these assumptions in 143 clinically-referred gifted children aged 8 to 12, using Wechsler's intelligence profile and the Child Behavior Checklist. Compared to a normative sample, gifted children displayed increased behavioral problems in the whole symptomatic range. Internalizing problems did not predominate over externalizing ones (i.e., acted-out problems, reflecting undercontrol of emotion and behavior), revealing a symptomatic nature of behavioral syndromes more severe than expected. "Highly gifted" children did not display more behavioral problems than the "low gifted." Gifted children with a significant verbal-performance discrepancy displayed more externalizing problems and mixed behavioral syndromes than gifted children without such a discrepancy. These results suggest that developmental asynchrony matters when examining emotional and behavioral problems in gifted children.

  11. Alkaline and neutral Comet assay profiles of sperm DNA damage in clinical groups.

    Science.gov (United States)

    Ribas-Maynou, J; García-Peiró, A; Abad, C; Amengual, M J; Navarro, J; Benet, J

    2012-03-01

    The analysis of sperm DNA fragmentation has become a new marker to predict male infertility, and many techniques have been developed. The sperm Comet assay offers the possibility of differentiating single- and double-stranded DNA (ssDNA and dsDNA) breaks, which could have different effects on fertility. The objective of this study was to perform a descriptive characterization of different groups of patients, such as those with asthenoteratozoospermic (ATZ) with or without varicocele, oligoasthenoteratozoospermic (OATZ) or balanced chromosome rearrangements, as compared with fertile donors. The Comet assay was used to investigate sperm samples for ssDNA and dsDNA breaks. The analysis of alkaline and neutral Comet assays in different groups of patients showed different sperm DNA damage profiles. Most fertile donors presented low values for ssDNA and dsDNA fragmentation (low-equivalent Comet profile), which would be the best prognosis for achieving a pregnancy. OATZ, ATZ and ATZ with varicocele presented high percentages of ssDNA and dsDNA fragmentation (high-equivalent Comet assay profile), ATZ with varicocele being associated with the worst prognosis, due to higher levels of DNA fragmentation. Rearranged chromosome carriers display a very high variability and, interestingly, two different profiles were seen: a high-equivalent Comet assay profile, which could be compatible with a bad prognosis, and a non-equivalent Comet assay profile, which has also been found in three fertile donors. Comet assay profiles, applied to different clinical groups, may be useful for determining prognosis in cases of male infertility.

  12. Predictive data mining in clinical medicine: Current issues and guidelines

    OpenAIRE

    Bellazzi, Riccado; Zupan, Blaz

    2008-01-01

    BACKGROUND: The widespread availability of new computational methods and tools for data analysis and predictive modeling requires medical informatics researchers and practitioners to systematically select the most appropriate strategy to cope with clinical prediction problems. In particular, the collection of methods known as 'data mining' offers methodological and technical solutions to deal with the analysis of medical data and construction of prediction models. A large variety of these met...

  13. Deep clonal profiling of formalin fixed paraffin embedded clinical samples.

    Directory of Open Access Journals (Sweden)

    Tara Holley

    Full Text Available Formalin fixed paraffin embedded (FFPE tissues are a vast resource of annotated clinical samples. As such, they represent highly desirable and informative materials for the application of high definition genomics for improved patient management and to advance the development of personalized therapeutics. However, a limitation of FFPE tissues is the variable quality of DNA extracted for analyses. Furthermore, admixtures of non-tumor and polyclonal neoplastic cell populations limit the number of biopsies that can be studied and make it difficult to define cancer genomes in patient samples. To exploit these valuable tissues we applied flow cytometry-based methods to isolate pure populations of tumor cell nuclei from FFPE tissues and developed a methodology compatible with oligonucleotide array CGH and whole exome sequencing analyses. These were used to profile a variety of tumors (breast, brain, bladder, ovarian and pancreas including the genomes and exomes of matching fresh frozen and FFPE pancreatic adenocarcinoma samples.

  14. Validation, updating and impact of clinical prediction rules: a review.

    Science.gov (United States)

    Toll, D B; Janssen, K J M; Vergouwe, Y; Moons, K G M

    2008-11-01

    To provide an overview of the research steps that need to follow the development of diagnostic or prognostic prediction rules. These steps include validity assessment, updating (if necessary), and impact assessment of clinical prediction rules. Narrative review covering methodological and empirical prediction studies from primary and secondary care. In general, three types of validation of previously developed prediction rules can be distinguished: temporal, geographical, and domain validations. In case of poor validation, the validation data can be used to update or adjust the previously developed prediction rule to the new circumstances. These update methods differ in extensiveness, with the easiest method a change in model intercept to the outcome occurrence at hand. Prediction rules -- with or without updating -- showing good performance in (various) validation studies may subsequently be subjected to an impact study, to demonstrate whether they change physicians' decisions, improve clinically relevant process parameters, patient outcome, or reduce costs. Finally, whether a prediction rule is implemented successfully in clinical practice depends on several potential barriers to the use of the rule. The development of a diagnostic or prognostic prediction rule is just a first step. We reviewed important aspects of the subsequent steps in prediction research.

  15. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    Science.gov (United States)

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A multi-institution evaluation of clinical profile anonymization.

    Science.gov (United States)

    Heatherly, Raymond; Rasmussen, Luke V; Peissig, Peggy L; Pacheco, Jennifer A; Harris, Paul; Denny, Joshua C; Malin, Bradley A

    2016-04-01

    There is an increasing desire to share de-identified electronic health records (EHRs) for secondary uses, but there are concerns that clinical terms can be exploited to compromise patient identities. Anonymization algorithms mitigate such threats while enabling novel discoveries, but their evaluation has been limited to single institutions. Here, we study how an existing clinical profile anonymization fares at multiple medical centers. We apply a state-of-the-artk-anonymization algorithm, withkset to the standard value 5, to the International Classification of Disease, ninth edition codes for patients in a hypothyroidism association study at three medical centers: Marshfield Clinic, Northwestern University, and Vanderbilt University. We assess utility when anonymizing at three population levels: all patients in 1) the EHR system; 2) the biorepository; and 3) a hypothyroidism study. We evaluate utility using 1) changes to the number included in the dataset, 2) number of codes included, and 3) regions generalization and suppression were required. Our findings yield several notable results. First, we show that anonymizing in the context of the entire EHR yields a significantly greater quantity of data by reducing the amount of generalized regions from ∼15% to ∼0.5%. Second, ∼70% of codes that needed generalization only generalized two or three codes in the largest anonymization. Sharing large volumes of clinical data in support of phenome-wide association studies is possible while safeguarding privacy to the underlying individuals. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Do Clinical Symptoms and Signs Predict Reduced Renal Function ...

    African Journals Online (AJOL)

    Renal dysfunction remains clinically asymptomatic, until late in the course of disease, and its symptoms and screening strategies are poorly defined. Aim: We conducted this study to understand if the presence of renal dysfunction related clinical symptom and signs (either alone or in combination) can predict reduced GFR.

  18. Prediction of Clinical Response in Children Taking Methylphenidate.

    Science.gov (United States)

    Aman, Michael G.; Turbott, Sarah H.

    1991-01-01

    Twenty-six children (ages 5-12) with attention deficit hyperactivity disorder were tested before and after treatment with methylphenidate. Few performance tests predicted clinical response to medication. Chronological age and performance on a memory distraction task and the Graduated Holes Task were moderately correlated with clinical outcome.…

  19. Infantile and early childhood masturbation: Sex hormones and clinical profile.

    Science.gov (United States)

    Ajlouni, Heitham K; Daoud, Azhar S; Ajlouni, Saleh F; Ajlouni, Kamel M

    2010-01-01

    Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography (n=8) and brain neuroimaging (n=9). We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin (SHBG), and androstenedione in all participants. The median age at the first incident was 19.5 months (range, 4-36 months); the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone (n=10) and supine positions (n=3); two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group (P=.02). Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings.

  20. Clinical profile of acute disseminated encephalomyelitis in children

    Science.gov (United States)

    Jayakrishnan, M.P.; Krishnakumar, P.

    2010-01-01

    Aim: To study the clinical profile of acute disseminated encephalomyelitis (ADEM) in children. Materials and Methods: All children admitted with ADEM during a period of one and a half years were included in the study. The diagnosis of ADEM was made based on the clinical presentation and suggestive MRI findings. All children were treated with intravenous methyl prednisolone, followed by oral prednisolone and followed up for varying periods up to three and a half years. Results: The sample consisted of 14 children with 11(79%) girls and 3 (21%) boys. The oldest child was 12 years and the youngest was a six-month-old infant. Acute febrile illness preceded the onset of neurological symptoms in 64% of children. The interval between the preceding illness and symptoms of ADEM varied from 7 days to 28 days (mean 12 days). The common presenting symptoms were fever, vomiting, headache, gait disturbance and generalized seizures. Neurological manifestations included altered sensorium, multiple cranial nerve involvement, quadriplegia and paraplegia, dystonia and choreiform movements, nystagmus, bladder involvement (both incontinence and retention), speech defect and double vision. Facial nerve was the most common cranial nerve involved. Psychological manifestations included aggressive behavior, psychotic symptoms and mood changes. One child each had features of acute psychotic episode and depressive episode. All children recovered fully. One child had multiphasic disseminated encephalomyelitis (MDEM) on follow up. Conclusion: Despite the serious neuropsychiatric manifestations, ADEM in children generally has good immediate outcome. Children with ADEM need long-term follow up for cognitive impairments. PMID:21559154

  1. Clinical and Demographic Profile of Attendees at Baghdad’s Walk-in Psychiatric Clinic

    Directory of Open Access Journals (Sweden)

    Maha S. Younis

    2013-09-01

    Full Text Available Objective: Few studies have examined clinical and demographic profile of attendees of a walk-in psychiatric clinic in countries ravaged by wars. The aim of this study is to quantify the characteristics of attendees of an open walk-in psychiatric clinic in a general hospital in Baghdad and the suburb towns of Iraq in the year 2010.Methods: As part of a retrospective survey, information on specific variables (socio-demographic background, clinical characteristics and attendance rate were sought from medical records in the year 2010 (January to December.Results: Despite the shortcomings expected from a country coming out of the ravage of war, the survey included 2,979 attendees (1,864 [63%] males and 1,115 [37%] females of a walk-in psychiatric clinic who fulfilled the inclusion criteria. The profile of attendees indicated that a majority of the cohort was self-referred with a predominance of employed males, aged 19 to 49 years, residing in Baghdad City. Depression and psychosis were the most common diagnosis given.Conclusion: The observed patterns are discussed within the available literature relevant to consultation liaison psychiatry, and specific to situations in Iraq and Arab/Islamic cultural patterning.

  2. Clinical Response to Vedolizumab in Ulcerative Colitis Patients Is Associated with Changes in Integrin Expression Profiles

    Directory of Open Access Journals (Sweden)

    Friederike Fuchs

    2017-07-01

    Full Text Available BackgroundDespite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear.MethodsBlood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells. Moreover, clinical and laboratory data from the patients were collected, and changes between homing marker expression and clinical parameters were analyzed for possible correlations.ResultsWhile no significant correlation of changes in integrin expression and changes in outcome parameters were identified in Crohn’s disease (CD, increasing α4β7 levels in ulcerative colitis (UC seemed to be associated with favorable clinical development, whereas increasing α4β1 and αEβ7 correlated with negative changes in outcome parameters. Changes in α4β1 integrin expression after 6 weeks were significantly different in responders and non-responders to vedolizumab therapy as assessed after 16 weeks with a cutoff of +4.2% yielding 100% sensitivity and 100% specificity in receiver-operator-characteristic analysis.DiscussionOur data show that clinical response to vedolizumab therapy in UC but not in CD is associated with specific changes in integrin expression profiles opening novel avenues for mechanistic research and possibly prediction of response to therapy.

  3. Clinical Response to Vedolizumab in Ulcerative Colitis Patients Is Associated with Changes in Integrin Expression Profiles.

    Science.gov (United States)

    Fuchs, Friederike; Schillinger, Daniela; Atreya, Raja; Hirschmann, Simon; Fischer, Sarah; Neufert, Clemens; Atreya, Imke; Neurath, Markus F; Zundler, Sebastian

    2017-01-01

    Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear. Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells. Moreover, clinical and laboratory data from the patients were collected, and changes between homing marker expression and clinical parameters were analyzed for possible correlations. While no significant correlation of changes in integrin expression and changes in outcome parameters were identified in Crohn's disease (CD), increasing α4β7 levels in ulcerative colitis (UC) seemed to be associated with favorable clinical development, whereas increasing α4β1 and αEβ7 correlated with negative changes in outcome parameters. Changes in α4β1 integrin expression after 6 weeks were significantly different in responders and non-responders to vedolizumab therapy as assessed after 16 weeks with a cutoff of +4.2% yielding 100% sensitivity and 100% specificity in receiver-operator-characteristic analysis. Our data show that clinical response to vedolizumab therapy in UC but not in CD is associated with specific changes in integrin expression profiles opening novel avenues for mechanistic research and possibly prediction of response to therapy.

  4. Clinical utility of gene-expression profiling in women with early breast cancer: an overview of systematic reviews.

    Science.gov (United States)

    Marrone, Michael; Stewart, Alison; Dotson, W David

    2015-07-01

    This overview systematically evaluates the clinical utility of using Oncotype DX and MammaPrint gene-expression profiling tests to direct treatment decisions in women with breast cancer. The findings are intended to inform an updated recommendation from the Evaluation of Genomic Applications in Practice and Prevention Working Group. Evidence reported in systematic reviews evaluating the clinical utility of Oncotype DX and MammaPrint, as well as the ability to predict treatment outcomes, change in treatment decisions, and cost-effectiveness, was qualitatively synthesized. Five systematic reviews found no direct evidence of clinical utility for either test. Indirect evidence showed Oncotype DX was able to predict treatment effects of adjuvant chemotherapy, whereas no evidence of predictive value was found for MammaPrint. Both tests influenced a change in treatment recommendations in 21 to 74% of participants. The cost-effectiveness of Oncotype DX varied with the alternative compared. For MammaPrint, lack of evidence of the predictive value led to uncertainty in the cost-effectiveness. No studies were identified that provided direct evidence that using gene-expression profiling tests to direct treatment decisions improved outcomes in women with breast cancer. Three ongoing studies may provide direct evidence for determining the clinical utility of gene-expression profiling testing.

  5. Imbalanced target prediction with pattern discovery on clinical data repositories.

    Science.gov (United States)

    Chan, Tak-Ming; Li, Yuxi; Chiau, Choo-Chiap; Zhu, Jane; Jiang, Jie; Huo, Yong

    2017-04-20

    Clinical data repositories (CDR) have great potential to improve outcome prediction and risk modeling. However, most clinical studies require careful study design, dedicated data collection efforts, and sophisticated modeling techniques before a hypothesis can be tested. We aim to bridge this gap, so that clinical domain users can perform first-hand prediction on existing repository data without complicated handling, and obtain insightful patterns of imbalanced targets for a formal study before it is conducted. We specifically target for interpretability for domain users where the model can be conveniently explained and applied in clinical practice. We propose an interpretable pattern model which is noise (missing) tolerant for practice data. To address the challenge of imbalanced targets of interest in clinical research, e.g., deaths less than a few percent, the geometric mean of sensitivity and specificity (G-mean) optimization criterion is employed, with which a simple but effective heuristic algorithm is developed. We compared pattern discovery to clinically interpretable methods on two retrospective clinical datasets. They contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the cardiac dataset, respectively. In spite of the imbalance challenge shown on other methods, pattern discovery consistently shows competitive cross-validated prediction performance. Compared to logistic regression, Naïve Bayes, and decision tree, pattern discovery achieves statistically significant (p-values data and tweaking, the prediction performance of pattern discovery is consistently comparable to the best achievable performance. Pattern discovery has demonstrated to be robust and valuable for target prediction on existing clinical data repositories with imbalance and noise. The prediction results and interpretable patterns can provide insights in an agile and inexpensive way for the potential formal studies.

  6. Different Cognitive Complaint Profiles in Memory Clinic and Depressive Patients.

    Science.gov (United States)

    Miebach, Lisa; Wolfsgruber, Steffen; Frommann, Ingo; Buckley, Rachel; Wagner, Michael

    2017-11-08

    Cognitive complaints are considered early indicators of incipient Alzheimer's disease (AD) but are very common in geriatric patients, especially in patients with major depressive disorder (MDD). The clinical assessment of cognitive complaints is still poorly operationalized. Recent qualitative research suggests that certain phenomenologic complaint themes may have some specificity for prodromal AD. The aim of the study was to replicate and explore their occurrence in a clinical setting. In a cross-sectional, case-control study using a mixed-methods approach, 23 memory clinic (cognitive complainers [CC]) patients, 21 psychiatric inpatients with MDD, and 21 healthy control subjects, aged 55-86 years, were assessed at the Department of Psychiatry and Psychotherapy and German Center for Neurodegenerative Diseases, Bonn. A newly developed semistructured interview addressing 12 complaint themes was used, and transcribed open format responses were coded by qualitative expert rating (theme absent versus present) and compared between the groups. Seven complaint themes (e.g., sense of predomination, progression) were significantly more often endorsed by the CC group, together with a novel theme of "distractible speech." Complaint themes in those with depression aligned with the depressive symptoms and appeared to be partly different from the complaint pattern of the CC group. Previously established themes were found to be feasible for conversion into a semistructured interview. Several complaint phenotypes were confirmed and previous themes significantly expanded by providing first evidence for a qualitatively different complaint profile in MDD compared with CC. Future investigations may benefit from better characterizing the phenomenologic and qualitative characteristics of AD-related complaints. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Clinical impact of extensive molecular profiling in advanced cancer patients.

    Science.gov (United States)

    Cousin, Sophie; Grellety, Thomas; Toulmonde, Maud; Auzanneau, Céline; Khalifa, Emmanuel; Laizet, Yec'han; Tran, Kevin; Le Moulec, Sylvestre; Floquet, Anne; Garbay, Delphine; Robert, Jacques; Hostein, Isabelle; Soubeyran, Isabelle; Italiano, Antoine

    2017-02-08

    Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0-9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19-88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3.Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.

  8. Compact Web browsing profiles for click-through rate prediction

    DEFF Research Database (Denmark)

    Fruergaard, Bjarne Ørum; Hansen, Lars Kai

    2014-01-01

    In real time advertising we are interested in finding features that improve click-through rate prediction. One source of available information is the bipartite graph of websites previously engaged by identifiable users. In this work, we investigate three different decompositions of such a graph...

  9. Chronic Liver Diseases in Children: Clinical Profile and Histology.

    Science.gov (United States)

    Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

    2015-07-01

    The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

  10. Geometrical theory to predict eccentric photorefraction intensity profiles in the human eye

    Science.gov (United States)

    Roorda, Austin; Campbell, Melanie C. W.; Bobier, W. R.

    1995-08-01

    In eccentric photorefraction, light returning from the retina of the eye is photographed by a camera focused on the eye's pupil. We use a geometrical model of eccentric photorefraction to generate intensity profiles across the pupil image. The intensity profiles for three different monochromatic aberration functions induced in a single eye are predicted and show good agreement with the measured eccentric photorefraction intensity profiles. A directional reflection from the retina is incorporated into the calculation. Intensity profiles for symmetric and asymmetric aberrations are generated and measured. The latter profile shows a dependency on the source position and the meridian. The magnitude of the effect of thresholding on measured pattern extents is predicted. Monochromatic aberrations in human eyes will cause deviations in the eccentric photorefraction measurements from traditional crescents caused by defocus and may cause misdiagnoses of ametropia or anisometropia. Our results suggest that measuring refraction along the vertical meridian is preferred for screening studies with the eccentric photorefractor.

  11. Effects of DTM resolution on slope steepness and soil loss prediction on hillslope profiles

    Science.gov (United States)

    Eder Paulo Moreira; William J. Elliot; Andrew T. Hudak

    2011-01-01

    Topographic attributes play a critical role in predicting erosion in models such as the Water Erosion Prediction Project (WEPP). The effects of four different high resolution hillslope profiles were studied using four different DTM resolutions: 1-m, 3-m, 5-m and 10-m. The WEPP model used a common scenario encountered in the forest environment and the selected hillslope...

  12. Clinical Outcome Prediction Using Single-Cell Data.

    Science.gov (United States)

    Pouyan, Maziyar Baran; Jindal, Vasu; Nourani, Mehrdad

    2016-10-01

    Single-cell technologies like flow cytometry (FCM) provide valuable biological data for knowledge discovery in complex cellular systems like tissues and organs. FCM data contains multi-dimensional information about the cellular heterogeneity of intricate cellular systems. It is possible to correlate single-cell markers with phenotypic properties of those systems. Cell population identification and clinical outcome prediction from single-cell measurements are challenging problems in the field of single cell analysis. In this paper, we propose a hybrid learning approach to predict clinical outcome using samples' single-cell FCM data. The proposed method is efficient in both i) identification of cellular clusters in each sample's FCM data and ii) predict clinical outcome (healthy versus unhealthy) for each subject. Our method is robust and the experimental results indicate promising performance.

  13. Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

    Science.gov (United States)

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

  14. Clinical profile of cerebral malaria at a secondary care hospital

    Directory of Open Access Journals (Sweden)

    Jency Maria Koshy

    2014-01-01

    Full Text Available Introduction: Cerebral malaria (CM is one of the most common causes for non-traumatic encephalopathy in the world. It affects both the urban and rural population. It is a challenge to treat these patients in a resource limited setting; where majority of these cases present. Materials and Methods: This was a prospective study carried out from September 2005 to December 2006 at Jiwan Jyoti Christian Hospital in Eastern Uttar Pradesh in India. This is a secondary level care with limited resources. We studied the clinical profile, treatment and outcome of all the patients above the age of 14 years diagnosed with CM. Results: There were a total of 53 patients with CM of which 38 (71.7% of them were females. Among them, 35 (66% patients were less than 30 years of age. The clinical features noted were seizure (39.62%, anemia (84.9%, icterus (16.98%, hypotension (13.2%, bleeding (3.7%, hepatomegaly (5.66%, splenomegaly (5.66%, non-cardiogenic pulmonary edema (16.98% and renal dysfunction (37.36%. Co-infection with Plasmodium vivax was present in 13 (24.53% of them. Treatment received included artesunin compounds or quinine. Median time of defervescence was 2 (interquartile range1-3. Complete recovery was achieved in 43 (81% of them. Two (3.7% of them died. Conclusion: CM, once considered to be a fatal disease has shown remarkable improvement in the outcome with the wide availability of artesunin and quinine components. To combat the malaria burden, physicians in resource limited setting should be well trained to manage these patients especially in the endemic areas. The key to management is early diagnosis and initiation of treatment based on a high index of suspicion. Anticipation and early recognition of the various complications are crucial.

  15. Clinical and psychoeducational profile of children with borderline intellectual functioning.

    Science.gov (United States)

    Karande, Sunil; Kanchan, Sandeep; Kulkarni, Madhuri

    2008-08-01

    To document the clinical profile and academic history of children with borderline intellectual functioning ("slow learners"); and to assess parental knowledge and attitudes regarding this condition. From November 2004 to April 2005, 55 children (35 boys, 20 girls) were diagnosed as slow learners based on current level of academic functioning and global IQ scores (71-84) done by the WISC test. Detailed clinical and academic history; and physical and neurological examination findings were noted. The parents were counseled about the diagnosis and the option of special education. The mean age of slow learners was 11.9 years (+/-SD 2.3, range 8-17). Eighteen (32.7%) children had a significant perinatal history, 15 (27.3%) had delayed walking, 17 (30.9%) had delayed talking, 17 (30.9%) had microcephaly, 34 (61.8%) had presence of soft neurologic signs, and 10 (18.2%) were on complementary and alternative medication therapy. There were no differentiating features between the two gender groups. Their chief academic problems were difficulty in writing (92.7%), overall poor performance in all subjects (89.1%), and difficulty in mathematics (76.4%). Forty-six (83.6%) children had failed in examinations, 34 (61.8%) had experienced grade retention, and 32 (58.2%) had behavior problems. Most parents (83.3%) were reluctant to consider the option of special education. Slow learners struggle to cope up with the academic demands of the regular classroom. They need to be identified at an early age and their parents counseled to understand their academic abilities.

  16. Demographic and clinical profile of nursing facility residents with gout.

    Science.gov (United States)

    Zarowitz, Barbara J; O'Shea, Terrence E

    2013-06-01

    To develop a demographic and clinical profile of nursing facility residents with a diagnosis of gout. Descriptive, retrospective database analysis. U.S. nursing facilities. Nursing facility residents with a diagnosis of gout. Minimum Data Set and prescription claims records of residents served by Omnicare, Inc., with an International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis of gout, for the time period of October 1, 2009, to September 30, 2010, were linked and de-identified. Acute gouty attacks were defined by a proxy measure of a ? 14-day course of oral nonsteroidal anti-inflammatory drugs (NSAIDs), oral or injectable steroids, or oral colchicine. In the 138,724 residents (36.8% male: 76.8% white, 11.6% black) evaluated, the incidence of gout was 1.8% (n = 2,487). Of those with gout, males and females were represented relatively equally. There were 1,420 (57.2%) residents 80 years of age or older. Two-thirds of residents with gout required at least extensive assistance with most activities of daily living. Comorbid conditions-hypertension (82.2%), diabetes mellitus (46.6%), arthritis (43.7%), and renal failure (22.4%)-were common. Pain was reported in 68.7% of residents. Allopurinol (60.2%), colchicine (18.6%), febuxostat (2.3%), probenecid (1.1%), and probenecid/colchicine (therapy was received by 75.8% of residents. Acute gouty attacks were noted in 38% of residents; 53%, 25.2%, and 21.8% received short-course treatment with oral or injectable steroids, oral colchicines, or oral NSAIDs, respectively. Despite the limitations of a retrospective database analysis, this study reveals that nursing facility residents with a diagnosis of gout have significant disease burden. Clinicians should be aware of the potential impact of this disease on physical functioning, pain, and falls in this often-frail population.

  17. Clinical and inheritance profiles of Kallmann syndrome in Jordan

    Directory of Open Access Journals (Sweden)

    Shegem Nadima S

    2004-10-01

    Full Text Available Abstract Background Proper management of patients with Kallmann syndrome (KS allows them to attain a normal reproductive health. The purpose of this study is to demonstrate the presentation modalities, phenotypes and the modes of inheritance among 32 patients with Kallmann syndrome in Jordan. Recognition of the syndrome allows for prompt proper management and provision of genetic counselling. Subjects Over a period of five years (1999–2004, the clinical and inheritance profiles of 26 male and 6 female patients with Kallmann syndrome from 12 families were evaluated at the National Center for Diabetes, Endocrinology and Genetics in Jordan. Results The patients belonged to twelve Jordanian and Palestinian families and their age at presentation ranged from 4 – 46 years. Nine boys aged 4–14 years presented with cryptorchidism and microphallus, all other males presented with delayed puberty, hypogonadism and/or infertility. The main presentation among six female patients was primary amenorrhea. Intrafamilial variability in clinical phenotype was specifically evident for renal abnormalities and sensorineural hearing impairment. Familial KS was diagnosed in 27 patients belonging to five families with the X-linked mode of inheritance and two families with the autosomal recessive mode of inheritance. Conclusions (1 the majority of cases in this study represented the X-linked form of KS, which might point to a high prevalence of Kal 1 gene in the population. (2 Genetic counselling helps these families to reach a diagnosis at an early age and to decide about their reproductive options. (3 Children presenting with cryptorchidism and microphallus in our population should be investigated for KS.

  18. Bacteriological profile and clinical predictors of ESBL neonatal sepsis.

    Science.gov (United States)

    Sharma, Deepak; Kumar, Chetan; Pandita, Aakash; Pratap, Oleti Tejo; Dasi, Teena; Murki, Srinivas

    2016-01-01

    Bacteriologic profile and risk factors for ESBL sepsis in newborns admitted to a Level III NICU. This was a retrospective observational study that enrolled newborns admitted to NICU with perinatal risk factors or clinical signs of sepsis and positive blood culture from January 2013 to August 2014. Blood cultures were done by BACTEC and ESBL production was evaluated from double-disc synergy method. Maternal, perinatal and neonatal risk factors were recorded from the case records and computerized information base. Mothers received cephalosporins for PPROM but its use was restricted in newborns for both probable and culture-positive sepsis. Among the infants with sepsis 24% had early-onset sepsis. The incidence of ESBL of early-onset Gram-negative sepsis (EOGNS) was 44.7% (n = 17 of 38) and it was 65% in late-onset Gram-negative sepsis (n = 84 of 129). The predominant ESBL-producing microbe responsible for neonatal sepsis was Klebsiella sp. Among newborns with EOGNS, the risk factors for the production of ESBL were preterm PROM (p = 0.004) and maternal exposure to antibiotics (p = 0.05). ESBL Gram-negative sepsis is a substantial problem in neonatal infections. Maternal exposure to cephalosporins and maternal PPROM are important risk factors for ESBL Gram-negative EOS.

  19. PELVIC FLOOR DYSFUNCTIONS: CLINICAL AND SOCIODEMOGRAPHIC PROFILE OF UROGYNECOLOGIC OUTPATIENTS

    Directory of Open Access Journals (Sweden)

    Cássia Fernandes Coelho

    2013-01-01

    Full Text Available This study aimed to assess the socio-demographic and clinical profile of urogynecologic outpatients of a public tertiary hospital in Fortaleza, Ceará. This is a cross-sectional study whose sample consisted of 85 women with pelvic floor dysfunction. The age ranged from 27 to 86 years old (mean: 53.8±14.2. Most patients were married (54.9%, weren’t working formally (40.0% and didn’t smoke (82.4%. Approximately half was in postmenopausal period (48.2%. Most of them were multiparous (89.4% by vaginal delivery (92.9%. The main complaint reported was urinary incontinence (74.1%, and mixed urinary incontinence (MUI was the most frequent (60.0%. Over half of the patients also had pelvic organ prolapse (75.3%, and the most common defect was from the anterior vaginal wall (55.3%. The majority (57.6% had some form of anorectal dysfunction: constipation (40%, tenesmus (37.6%, fecal incontinence (16.5%. Most of the patients lost urine several times a day (57.3%, with impact on quality of life. The risk factors found are in agreement with literature data, as well as the prevalence of MUI. Given the concomitant disorders, it’s important to address all pathologies, because they are prevalent conditions with medical, social, psychological and economic implications.

  20. A Clinical Profile of 125 Patients with Writer's Cramp.

    Science.gov (United States)

    Jhunjhunwala, Ketan; Lenka, Abhishek; Pal, Pramod Kumar

    2015-01-01

    The characteristics of writer's cramp (WC) may vary according to native languages and scripts. We report the clinical profile of a large cohort of patients with WC from India. A chart review of 125 patients (F:M = 16:109) with WC seen over 10 years at the National Institute of Mental Health and Neurosciences (NIMHANS), India. The mean age of patients was 36.8 ± 14.3, the mean age at onset (AAO) of symptoms was 31.5 ± 2.7 and the mean duration of difficulty in writing was 5.3 ± 6.3. The most common presenting complaint while writing was pain in the forearm (56%), followed by tremulousness of hand (28.8%) and abnormal posturing of hand (15.2%). Along with writing difficulty, 5.6% had difficulty in typing. The mean AAO of writing difficulty was significantly earlier in women than in men (22.8 ± 3.5 vs. 32.8 ± 4.2 years, p writing, excessive extension (41.6%) of wrist was the most common abnormality, followed by excessive flexion (37.6%) and extension (19.2%) of index finger. Women with WC have a significantly earlier age of onset than men. Excessive extension of wrist with flexion of thumb and index finger were the most common abnormalities noted in WC. © 2015 S. Karger AG, Basel.

  1. A clinical predictive score for postoperative myasthenic crisis.

    Science.gov (United States)

    Kanai, Tetsuya; Uzawa, Akiyuki; Sato, Yasunori; Suzuki, Shigeaki; Kawaguchi, Naoki; Himuro, Keiichi; Oda, Fumiko; Ozawa, Yukiko; Nakahara, Jin; Suzuki, Norihiro; Takahashi, Yuko K; Ishibashi, Satoru; Yokota, Takanori; Ogawa, Takashi; Yokoyama, Kazumasa; Hattori, Nobutaka; Izaki, Shoko; Oji, Satoru; Nomura, Kyoichi; Kaneko, Juntaro; Nishiyama, Kazutoshi; Yoshino, Ichiro; Kuwabara, Satoshi

    2017-10-30

    Myasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor (AChR) associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis. We studied 393 patients with MG who underwent thymectomy at six tertiary centers in Japan (275 patients for derivation and 118 for validation). Clinical characteristics, such as gender, age at onset and operation, body mass index, disease duration, MG subtype, severity, symptoms, preoperative therapy, operative data, and laboratory data, were reviewed retrospectively. A multivariate logistic regression with LASSO penalties was used to determine the factors associated with postoperative myasthenic crisis and score was assigned. Finally, the predictive score was evaluated using bootstrapping technique in the derivation and validation group. Multivariate logistic regression identified three clinical factors for predicting postoperative myasthenic crisis risk: (1) vital capacity crisis predictive score, ranging from 0 to 6 points, had areas under the curve of 0.84 (0.66 - 0.96) in the derivation group and 0.80 (0.62 - 0.95) in the validation group. A simple scoring system based on three preoperative clinical characteristics can predict the possibility of postoperative myasthenic crisis. This article is protected by copyright. All rights reserved. © 2017 American Neurological Association.

  2. Adaptive parametric prediction of event times in clinical trials.

    Science.gov (United States)

    Lan, Yu; Heitjan, Daniel F

    2018-01-01

    In event-based clinical trials, it is common to conduct interim analyses at planned landmark event counts. Accurate prediction of the timing of these events can support logistical planning and the efficient allocation of resources. As the trial progresses, one may wish to use the accumulating data to refine predictions. Available methods to predict event times include parametric cure and non-cure models and a nonparametric approach involving Bayesian bootstrap simulation. The parametric methods work well when their underlying assumptions are met, and the nonparametric method gives calibrated but inefficient predictions across a range of true models. In the early stages of a trial, when predictions have high marginal value, it is difficult to infer the form of the underlying model. We seek to develop a method that will adaptively identify the best-fitting model and use it to create robust predictions. At each prediction time, we repeat the following steps: (1) resample the data; (2) identify, from among a set of candidate models, the one with the highest posterior probability; and (3) sample from the predictive posterior of the data under the selected model. A Monte Carlo study demonstrates that the adaptive method produces prediction intervals whose coverage is robust within the family of selected models. The intervals are generally wider than those produced assuming the correct model, but narrower than nonparametric prediction intervals. We demonstrate our method with applications to two completed trials: The International Chronic Granulomatous Disease study and Radiation Therapy Oncology Group trial 0129. Intervals produced under any method can be badly calibrated when the sample size is small and unhelpfully wide when predicting the remote future. Early predictions can be inaccurate if there are changes in enrollment practices or trends in survival. An adaptive event-time prediction method that selects the model given the available data can give improved

  3. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Directory of Open Access Journals (Sweden)

    Fine Howard A

    2010-07-01

    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  4. Clinical impact of extensive molecular profiling in advanced cancer patients

    Directory of Open Access Journals (Sweden)

    Sophie Cousin

    2017-02-01

    Full Text Available Abstract Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0–9. The most common primary tumour types were lung (16.9%, colorectal (14.4%, breast (10.6%, ovarian (10.2% and sarcoma (10.2%. The median patient age was 63 years (range 19–88. A total of 292 patients (51.4% presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28% were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%. The two main reasons for non-inclusion were non-progressive disease (31.5% and general status deterioration (25%. Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment >1.3. Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.

  5. Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets.

    Directory of Open Access Journals (Sweden)

    Kosuke Yoshihara

    Full Text Available BACKGROUND: Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. METHODOLOGY/PRINCIPAL FINDINGS: Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01 and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR, 3.72; 95% confidence interval (CI, 2.66-5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008. Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008. CONCLUSIONS/SIGNIFICANCE: The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.

  6. Clinical and pulmonary functions profiling of patients with chronic obstructive pulmonary disease experiencing frequent acute exacerbations

    Directory of Open Access Journals (Sweden)

    Prem Parkash Gupta

    2018-01-01

    Full Text Available Purpose: The present study aimed at clinical and pulmonary functions profiling of patients with chronic obstructive pulmonary disease (COPD to anticipate future exacerbations. Methods: The study included 80 COPD patients; 40 patients had ≥2 acute exacerbations during preceding 1 year (frequent exacerbation [FECOPD] group and 40 patients had <2 acute exacerbations during preceding 1 year (infrequent exacerbation [I-FECOPD] group. Clinical profile, sputum microbiology, blood gas analysis, spirometric indices, and diffusion capacity (transfer test variables were assessed. Groups' comparison was performed using an independent t-test for numeric scale parameters and Chi-square test for nominal parameters. Pearson's and Spearman's correlation coefficients were derived for numeric scale parameters and numeric nominal parameters, respectively. Multinomial logistic regression analysis was done using SPSS software. Results: FECOPD group contained younger patients than in I-FECOPD group although the difference was not statistically significant. There was no significant difference between two groups regarding smoking pack-years and duration of illness. FECOPD group had significantly more expectoration score and Modified Medical Research Council dyspnea scores. Cough score and wheeze score did not differ significantly between two groups. More patients in FECOPD group (12/40 vs. 4/40 had lower airway bacterial colonization. Arterial blood gas parameters were more deranged in FECOPD group. Spirometric indices (forced expiratory volume during 1st s as well as transfer test (both diffusing capacity for carbon monoxide and transfer coefficient of the lung values were significantly reduced in FECOPD group. Conclusions: The patients in FECOPD group had clinical, spirometric, and transfer test profiling suggestive of a severe COPD phenotype, the recognition will help in predicting future exacerbations and a better management.

  7. Use of Admissions Interview Comments to Predict Clinical Clerkship Success.

    Science.gov (United States)

    Baker, Helen Hicks; Dunlap, Margaret Reed

    The use of admission interview comments to predict clinical clerkship success of medical students was evaluated. Narrative comments made by admissions interviewers regarding an applicant's skills and attitudes were coded, as were narrative evaluations of these students during year III of required clerkships in pediatrics and internal medicine in…

  8. Meaning in life : Clinical relevance and predictive power

    NARCIS (Netherlands)

    Debats, DL

    1996-01-01

    The clinical relevance of the meaning in life construct is examined by evaluating its ability to predict patients' general and psychological well-being and their posttreatment functioning. Evidence is obtained for the notion that meaning in Life (a) would affect both positive and negative aspects of

  9. Clinical profile of patients with nascent alcohol related seizures

    Directory of Open Access Journals (Sweden)

    P Sandeep

    2013-01-01

    Full Text Available Aim: The aim of this study is to characterize the clinical profile of patients with alcohol related seizures (ARS and to identify the prevalence of idiopathic generalized epilepsy (IGE in the same. Materials and Methods: 100 consecutive male patients presenting to a tertiary care center in South India with new onset ARS were analyzed with alcohol use disorders identification test (AUDIT score. All underwent 19 channel digital scalp electroencephalography (EEG and at least computed tomography (CT scan. Results: A total of 27 patients (27% who had cortical atrophy on CT had a mean duration of alcohol intake of 23.62 years compared with 14.55 years in patients with no cortical atrophy (P < 0.001. Twenty-two patients (22% had clustering in the current episode of whom 18 had cortical atrophy. Nearly, 88% patients had generalized tonic clonic seizures while 12% who had partial seizures underwent magnetic resonance imaging (MRI, which identified frontal focal cortical dysplasia in one. Mean lifetime duration of alcohol intake in patients presenting with seizures within 6 hours (6H-gp of intake of alcohol was significantly lower (P = 0.029. One patient in the 6H-gp with no withdrawal symptoms had EEG evidence for IGE and had a lower AUDIT score compared with the rest. Conclusion: CT evidence of cortical atrophy is related to the duration of alcohol intake and portends an increased risk for clustering. Partial seizures can be a presenting feature of ARS and those patients may benefit from MRI to identify underlying symptomatic localization related epilepsy (8.3% of partial seizures. IGE is more likely in patients presenting with ARS within first 6 hours especially if they do not have alcohol withdrawal symptoms and scalp EEG is helpful to identify this small subgroup (~1% who may require long-term anti-epileptic medication.

  10. Malarial hepatopathy: Clinical profile and association with other malarial complications.

    Science.gov (United States)

    Jain, Anshika; Kaushik, Reshma; Kaushik, Rajeev Mohan

    2016-07-01

    This prospective study assessed the incidence, clinical profile and outcome of malarial hepatopathy and its association with other complications in patients with malaria, proved by peripheral blood smear examination and rapid malaria test. Hyperbilirubinemia (Serum bilirubin >3mg/dL) with >3-fold rise in serum aminotransferases in absence of a different explanation for such derangement was considered as malarial hepatopathy. Of 134 (falciparum-81, vivax-48 and mixed falciparum and vivax-5) malaria cases, hyperbilirubinemia occurred in 41.04%. Serum aspartate aminotransferase (AST) was raised >3-fold in 17.16% and serum alanine aminotransferase (ALT) in 4.47% cases. Malarial hepatopathy was observed in 4.47% (falciparum-5 and vivax malaria-1) cases, but had insignificant association with the type of malaria (p=0.532). Serum bilirubin, AST and ALT levels were higher while age was lower in both overall (pcases with hepatopathy than without hepatopathy (pcases (p>0.05 each). Mortality occurred in 1 (20%) case of falciparum-induced hepatopathy with an overall mortality of 16.66%. ARDS (p=0.003) and shock (p=0.026) were independently associated with malarial hepatopathy overall while only ARDS with falciparum-induced hepatopathy (p=0.006). Thus, hepatocellular dysfunction is common in malaria but that qualifying as malarial hepatopathy is not common. Malarial hepatopathy is likely to occur in presence of other malarial complications. It is an epiphenomenon in severe malaria and indicative of severe disease. Establishing a particular association with malaria or mortality would require a larger case-control study of severe malaria. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Neuropsychological profiles in individuals at clinical high risk for psychosis: relationship to psychosis and intelligence.

    Science.gov (United States)

    Woodberry, Kristen A; Seidman, Larry J; Giuliano, Anthony J; Verdi, Mary B; Cook, William L; McFarlane, William R

    2010-11-01

    Characterizing neuropsychological (NP) functioning of individuals at clinical high risk (CHR) for psychosis may be useful for prediction of psychosis and understanding functional outcome. The degree to which NP impairments are associated with general cognitive ability and/or later emergence of full psychosis in CHR samples requires study with well-matched controls. We assessed NP functioning across eight cognitive domains in a sample of 73 CHR youth, 13 of whom developed psychotic-level symptoms after baseline assessment, and 34 healthy comparison (HC) subjects. Groups were matched on age, sex, ethnicity, handedness, subject and parent grade attainment, and median family income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ. Profile analysis was used to examine group differences and the role of IQ in profile shape. The CHR sample demonstrated a significant difference in overall magnitude of NP impairment but only a small and nearly significant difference in profile shape, primarily due to a large impairment in olfactory identification. Individuals who subsequently developed psychotic-level symptoms demonstrated large impairments in verbal IQ, verbal memory and olfactory identification comparable in magnitude to first episode samples. CHR status may be associated with moderate generalized cognitive impairments marked by some degree of selective impairment in olfaction and verbal memory. Impairments were greatest in those who later developed psychotic symptoms. Future study of olfaction in CHR samples may enhance early detection and specification of neurodevelopmental mechanisms of risk. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. A Model for the Prediction of Tobacco Temperature and Oxygen Profiles in Warehouse Aging Process

    Directory of Open Access Journals (Sweden)

    Zheng Y

    2014-12-01

    Full Text Available A mathematical model on the temperature and oxygen profiles for the tobacco warehouse aging process was formulated and solved by numeric analysis. The model parameters were obtained using the non-linear regression method by fitting several years measured temperatures to the model. The R square value between measured and calculated tobacco temperatures in warehouse aging process are all over 0.95. The proposed model can be used to predict the tobacco hogshead temperature profile at different time and positions with ambient temperature, tobacco moisture contents and pH. At the same time, the model also predicts the oxygen profile in the hogshead. The effects of the ambient temperature, pH, void fraction, the reaction active energy, oxygen diffusivity, and the oxygen consumption rate constant on the temperature profile were studied.

  13. Connecting clinical and actuarial prediction with rule-based methods.

    Science.gov (United States)

    Fokkema, Marjolein; Smits, Niels; Kelderman, Henk; Penninx, Brenda W J H

    2015-06-01

    Meta-analyses comparing the accuracy of clinical versus actuarial prediction have shown actuarial methods to outperform clinical methods, on average. However, actuarial methods are still not widely used in clinical practice, and there has been a call for the development of actuarial prediction methods for clinical practice. We argue that rule-based methods may be more useful than the linear main effect models usually employed in prediction studies, from a data and decision analytic as well as a practical perspective. In addition, decision rules derived with rule-based methods can be represented as fast and frugal trees, which, unlike main effects models, can be used in a sequential fashion, reducing the number of cues that have to be evaluated before making a prediction. We illustrate the usability of rule-based methods by applying RuleFit, an algorithm for deriving decision rules for classification and regression problems, to a dataset on prediction of the course of depressive and anxiety disorders from Penninx et al. (2011). The RuleFit algorithm provided a model consisting of 2 simple decision rules, requiring evaluation of only 2 to 4 cues. Predictive accuracy of the 2-rule model was very similar to that of a logistic regression model incorporating 20 predictor variables, originally applied to the dataset. In addition, the 2-rule model required, on average, evaluation of only 3 cues. Therefore, the RuleFit algorithm appears to be a promising method for creating decision tools that are less time consuming and easier to apply in psychological practice, and with accuracy comparable to traditional actuarial methods. (c) 2015 APA, all rights reserved).

  14. An audit of the clinical profile of snake bites among female patients ...

    African Journals Online (AJOL)

    Background: A lot of work had been done on the clinical profiles of patients with snake bites but none on female patients alone. In this medical audit, we undertook to study the clinical profiles of snake bites among female patients seen over a two year period at a federal Government designated treatment centre, Zamko.

  15. Hidden Markov model to predict the amino acid profile

    Science.gov (United States)

    Handamari, Endang Wahyu

    2017-12-01

    Sequence alignment is the basic method in sequence analysis, which is the process of composing or aligning two or more primary sequences so that the sequence similarity is apparent. One of the uses of this method is to predict the structure or function of an unknown protein by using a known protein information structure or function if the protein has the same sequence in database. Protein are macromolecules that make up more than half of the cell. Proteins are a chain of 20 amino acid combinations. Each type of protein has a unique number and sequence of amino acids. The method that can be applied for sequence alignment is the Genetic Algorithm, the other method is related to the Hidden Markov Model (HMM). The Hidden Markov Model (HMM) is a developmental form of the Markov Chain, which can be applied in cases that can not be directly observed. As Observed State (O) for sequence alignment is the sequence of amino acids in three categories: deletion, insertion and match. As for the Hidden State is the amino acid residue, which can determine the family protein corresponds to observation O.

  16. Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis.

    Science.gov (United States)

    Gori, Anna Maria; Giusti, Betti; Piccardi, Benedetta; Nencini, Patrizia; Palumbo, Vanessa; Nesi, Mascia; Nucera, Antonia; Pracucci, Giovanni; Tonelli, Paolina; Innocenti, Eleonora; Sereni, Alice; Sticchi, Elena; Toni, Danilo; Bovi, Paolo; Guidotti, Mario; Tola, Maria Rosaria; Consoli, Domenico; Micieli, Giuseppe; Tassi, Rossana; Orlandi, Giovanni; Sessa, Maria; Perini, Francesco; Delodovici, Maria Luisa; Zedde, Maria Luisa; Massaro, Francesca; Abbate, Rosanna; Inzitari, Domenico

    2017-09-01

    Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19-7.53); SAP:5.46 (1.64-18.74); Δmetalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.

  17. Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learning.

    Science.gov (United States)

    Drozdov, Ignat; Kidd, Mark; Nadler, Boaz; Camp, Robert L; Mane, Shrikant M; Hauso, Oyvind; Gustafsson, Bjorn I; Modlin, Irvin M

    2009-04-15

    A more accurate taxonomy of small intestinal (SI) neuroendocrine tumors (NETs) is necessary to accurately predict tumor behavior and prognosis and to define therapeutic strategy. In this study, the authors identified a panel of such markers that have been implicated in tumorigenicity, metastasis, and hormone production and hypothesized that transcript levels of the genes melanoma antigen family D2 (MAGE-D2), metastasis-associated 1 (MTA1), nucleosome assembly protein 1-like (NAP1L1), Ki-67 (a marker of proliferation), survivin, frizzled homolog 7 (FZD7), the Kiss1 metastasis suppressor (Kiss1), neuropilin 2 (NRP2), and chromogranin A (CgA) could be used to define primary SI NETs and to predict the development of metastases. Seventy-three clinically and World Health Organization pathologically classified NET samples (primary tumor, n = 44 samples; liver metastases, n = 29 samples) and 30 normal human enterochromaffin (EC) cell preparations were analyzed using real-time polymerase chain reaction. Transcript levels were normalized to 3 NET housekeeping genes (asparagine-linked glycosylation 9 or ALG9, transcription factor CP2 or TFCP2, and zinc finger protein 410 or ZNF410) using geNorm analysis. A predictive gene-based model was constructed using supervised learning algorithms from the transcript expression levels. Primary SI NETs could be differentiated from normal human EC cell preparations with 100% specificity and 92% sensitivity. Well differentiated NETs (WDNETs), well differentiated neuroendocrine carcinomas, and poorly differentiated NETs (PDNETs) were classified with a specificity of 78%, 78%, and 71%, respectively; whereas poorly differentiated neuroendocrine carcinomas were misclassified as either WDNETs or PDNETs. Metastases were predicted in all cases with 100% sensitivity and specificity. The current results indicated that gene expression profiling and supervised machine learning can be used to classify SI NET subtypes and accurately predict metastasis

  18. Predictive models of syncope causes in an outpatient clinic.

    Science.gov (United States)

    Graf, D; Schlaepfer, J; Gollut, E; van Melle, G; Mischler, C; Fromer, M; Kappenberger, L; Pruvot, E

    2008-01-24

    The investigation of unexplained syncope remains a challenging clinical problem. In the present study we sought to evaluate the diagnostic value of a standardized work-up focusing on non invasive tests in patients with unexplained syncope referred to a syncope clinic, and whether certain combinations of clinical parameters are characteristic of rhythmic and reflex causes of syncope. 317 consecutive patients underwent a standardized work-up including a 12-lead ECG, physical examination, detailed history with screening for syncope-related symptoms using a structured questionnaire followed by carotid sinus massage (CSM), and head-up tilt test. Invasive testings including an electrophysiological study and implantation of a loop recorder were only performed in those with structural heart disease or traumatic syncope. Our work-up identified an etiology in 81% of the patients. Importantly, three quarters of the causes were established non invasively combining head-up tilt test, CSM and hyperventilation testing. Invasive tests yielded an additional 7% of diagnoses. Logistic analysis identified age and number of significant prodromes as the only predictive factors of rhythmic syncope. The same two factors, in addition to the duration of the ECG P-wave, were also predictive of vasovagal and psychogenic syncope. These factors, optimally combined in predictive models, showed a high negative and a modest positive predictive value. A standardized work-up focusing on non invasive tests allows to establish more than three quarters of syncope causes. Predictive models based on simple clinical parameters may help to distinguish between rhythmic and other causes of syncope.

  19. Clinical gestalt and the prediction of massive transfusion after trauma.

    Science.gov (United States)

    Pommerening, Matthew J; Goodman, Michael D; Holcomb, John B; Wade, Charles E; Fox, Erin E; Del Junco, Deborah J; Brasel, Karen J; Bulger, Eileen M; Cohen, Mitch J; Alarcon, Louis H; Schreiber, Martin A; Myers, John G; Phelan, Herb A; Muskat, Peter; Rahbar, Mohammad; Cotton, Bryan A

    2015-05-01

    Early recognition and treatment of trauma patients requiring massive transfusion (MT) has been shown to reduce mortality. While many risk factors predicting MT have been demonstrated, there is no universally accepted method or algorithm to identify these patients. We hypothesised that even among experienced trauma surgeons, the clinical gestalt of identifying patients who will require MT is unreliable. Transfusion and mortality outcomes after trauma were observed at 10 U.S. Level-1 trauma centres in patients who survived ≥ 30 min after admission and received ≥ 1 unit of RBC within 6h of arrival. Subjects who received ≥ 10 units within 24h of admission were classified as MT patients. Trauma surgeons were asked the clinical gestalt question "Is the patient likely to be massively transfused?" 10 min after the patients arrival. The performance of clinical gestalt to predict MT was assessed using chi-square tests and ROC analysis to compare gestalt to previously described scoring systems. Of the 1245 patients enrolled, 966 met inclusion criteria and 221 (23%) patients received MT. 415 (43%) were predicted to have a MT and 551(57%) were predicted to not have MT. Patients predicted to have MT were younger, more often sustained penetrating trauma, had higher ISS scores, higher heart rates, and lower systolic blood pressures (all pGestalt sensitivity was 65.6% and specificity was 63.8%. PPV and NPV were 34.9% and 86.2% respectively. Data from this large multicenter trial demonstrates that predicting the need for MT continues to be a challenge. Because of the increased mortality associated with delayed therapy, a more reliable algorithm is needed to identify and treat these severely injured patients earlier. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Arm exercise stress perfusion imaging predicts clinical outcome.

    Science.gov (United States)

    Chan, Albert K; Ilias-Khan, Nasreen A; Xian, Hong; Inman, Cindi; Martin, Wade H

    2011-12-01

    Treadmill exercise capacity in resting metabolic equivalents (METs) and stress hemodynamic, electrocardiographic (ECG), and myocardial perfusion imaging (MPI) responses are independently predictive of adverse clinical events. However, limited data exist for arm ergometer stress testing (AXT) in patients who cannot perform leg exercise because of lower extremity disabilities. We sought to determine the extent to which AXT METs, hemodynamic, ECG, and MPI responses to arm exercise add independent incremental value to demographic and clinical variables for prediction of all-cause mortality, myocardial infarction (MI), or late coronary revascularization, individually or as a composite. A prospective cohort of 186 patients aged 64 ± 10 (SD) yr, unable to perform lower extremity exercise, underwent AXT MPI for clinical reasons between 1997 and 2002, and were followed for 62 ± 23 mo, to an endpoint of death or 12/31/2006. Average annual rates were 5.4% for mortality, 2.2% for MI, 2.5% for late coronary revascularization, and 8.0% for combined events. After adjustment for age and clinical variables, AXT METs [P ECG (P ECG (P leg exercise because of lower extremity disabilities, AXT METs are as important as MPI for prediction of mortality alone and death and MI combined, and a positive AXT ECG prognosticates MI alone and death and MI combined.

  1. [Predictive ability of clinical parameters of bacteremia in hemodialysed patients].

    Science.gov (United States)

    Egea, Ana L; Vilaró, Mario; De la Fuente, Jorge; Cuestas, Eduardo; Bongiovanni, María E

    2012-01-01

    No clinical events to differentiate bacteteremia from other pathologies in hemodialysis patients therefore the physicians makes diagnosis and treatment decisions based on clinical evidence an local epidemiology. the aim of this work was to study the frequency of microorganism isolated from blood culture of hemodialysis patients with suspected bacteraemia and evaluate Sensitivity (S) and Specificity (E) of medical diagnostic orientation in this cases of suspected Materials and methods: we performed an observational and prospective study for one year in hemodialysis patient with suspected bacteremia. We evaluated blood pressure, temperature (Tº), altered conscious state (AEC), respiratory frequency (FR), chills (ESC),diarrhea (DIARR), blood culture results and microbiological identification. We work with the mean ± standar desviation for continuous variables and frequencies for categorical variables We analyzed S, E, negative predictive value (VPN), positive predictive value (VPP) RESULTADOS: a total of 87 events with suspected bacteremia 34 (39%) were confirmed with positive blood culture the most common microorganisms were cocci Gram positive (CGP) 65%, Most relevant clinical variables were PCP ≥ 2 (VPN 81%), Tº ≥ 38 (VPN 76%) and AEC (E 98% y VPP 80%). CGP were the most prevalent microorganisms None of the clinical variables shows high S and E indicating low usefulness as a predictive tool of bacteremia Excepting AEC with E98% and VPP 80% but it would be necessary to evaluate this variable with a more number patient. Results justify to routine HC use like diagnostic tool.

  2. Clinical Profile of Atypical Manifestations of Dengue Fever.

    Science.gov (United States)

    Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

    2016-06-01

    To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. All children (0-12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of

  3. Tubercular meningitis in children: Clinical, pathological, and radiological profile and factors associated with mortality.

    Science.gov (United States)

    Israni, Anil V; Dave, Divya A; Mandal, Anirban; Singh, Amitabh; Sahi, Puneet K; Das, Rashmi Ranjan; Shah, Arpita

    2016-01-01

    Childhood tuberculosis is a major public health problem in developing countries with tubercular meningitis being a serious complication with high mortality and morbidity. To study the clinicopathological as well as radiological profile of childhood tuberculous meningitis (TBM) cases. Prospective, observational study including children analysis. Various risk factors were determined using Chi-square tests, and a P< 0.05 was considered significant. Forty-seven children were included, of which 11 (24.3%) died. Fever was the most common presenting symptom, and meningismus was the most common sign. Twenty-nine (62%) children presented with Stage III disease. Stage III disease, low GCS, and raised ICP were predictors of mortality. Findings on neuroimaging or CSF examination did not predict mortality. Childhood TBM presents with nonspecific clinical features. Stage III disease, low GCS, lack of Bacillus Calmette-Guérin vaccination at birth and raised ICP seem to the most important adverse prognostic factors.

  4. Predicting reattendance at a high-risk breast cancer clinic.

    Science.gov (United States)

    Ormseth, Sarah R; Wellisch, David K; Aréchiga, Adam E; Draper, Taylor L

    2015-10-01

    The research about follow-up patterns of women attending high-risk breast-cancer clinics is sparse. This study sought to profile daughters of breast-cancer patients who are likely to return versus those unlikely to return for follow-up care in a high-risk clinic. Our investigation included 131 patients attending the UCLA Revlon Breast Center High Risk Clinic. Predictor variables included age, computed breast-cancer risk, participants' perceived personal risk, clinically significant depressive symptomatology (CES-D score ≥ 16), current level of anxiety (State-Trait Anxiety Inventory), and survival status of participants' mothers (survived or passed away from breast cancer). A greater likelihood of reattendance was associated with older age (adjusted odds ratio [AOR] = 1.07, p = 0.004), computed breast-cancer risk (AOR = 1.10, p = 0.017), absence of depressive symptomatology (AOR = 0.25, p = 0.009), past psychiatric diagnosis (AOR = 3.14, p = 0.029), and maternal loss to breast cancer (AOR = 2.59, p = 0.034). Also, an interaction was found between mother's survival and perceived risk (p = 0.019), such that reattendance was associated with higher perceived risk among participants whose mothers survived (AOR = 1.04, p = 0.002), but not those whose mothers died (AOR = 0.99, p = 0.685). Furthermore, a nonlinear inverted "U" relationship was observed between state anxiety and reattendance (p = 0.037); participants with moderate anxiety were more likely to reattend than those with low or high anxiety levels. Demographic, medical, and psychosocial factors were found to be independently associated with reattendance to a high-risk breast-cancer clinic. Explication of the profiles of women who may or may not reattend may serve to inform the development and implementation of interventions to increase the likelihood of follow-up care.

  5. Comparison of gene sets for expression profiling: prediction of metastasis from low-malignant breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Eiriksdottir, Freyja

    2007-01-01

    -six tumors from low-risk patients and 34 low-malignant T2 tumors from patients with slightly higher risk have been examined by genome-wide gene expression analysis. Nine prognostic gene sets were tested in this data set. RESULTS: A 32-gene profile (HUMAC32) that accurately predicts metastasis has previously...... sets, mainly developed in high-risk cancers, predict metastasis from low-malignant cancer....

  6. Within treatment therapeutic alliance ratings profiles predict posttreatment frequency of alcohol use.

    Science.gov (United States)

    Prince, Mark A; Connors, Gerard J; Maisto, Stephen A; Dearing, Ronda L

    2016-03-01

    Although past research has demonstrated a positive relationship between the therapeutic alliance (TA) and improved drinking outcomes, specific aspects of the alliance have received less attention. In this study, we examined the association between alliance characteristics during treatment and 4-month follow-up drinking reports. Sixty-five treatment-seeking alcohol dependent clients who participated in 12 weeks of individual outpatient treatment provided weekly TA ratings during treatment and reported on pretreatment, during treatment, and posttreatment alcohol use. Latent profile analysis was conducted to discern distinct profiles of client and therapist ratings of therapeutic alliance with similar alliance characteristics. TA profiles were based on clients' and therapists' mean alliance rating, minimum alliance rating, maximum alliance rating, the range of alliance ratings, and the difference in session number between maximum and minimum alliance ratings. One- through 4-class models were fit to the data. Model fit was judged by comparative fit indices, substantive interpretability, and parsimony. Wald tests of mean equality determined whether classes differed on follow-up percentage of days abstinent (PDA) at 4-months posttreatment. Three-profile solutions provided the best fit for both client and therapist ratings of the therapeutic alliance. Client alliance rating profiles predicted drinking in the follow-up period, but therapist rating profiles did not. These results suggest that distinct profiles of the therapeutic alliance can be identified and that client alliance rating profiles are associated with frequency of alcohol use following outpatient treatment. (c) 2016 APA, all rights reserved).

  7. Technical player profiles related to the physical fitness of young female volleyball players predict team performance.

    Science.gov (United States)

    Dávila-Romero, C; Hernández-Mocholí, M A; García-Hermoso, A

    2015-03-01

    This study is divided into three sequential stages: identification of fitness and game performance profiles (individual player performance), an assessment of the relationship between these profiles, and an assessment of the relationship between individual player profiles and team performance during play (in championship performance). The overall study sample comprised 525 (19 teams) female volleyball players aged 12-16 years and a subsample (N.=43) used to examine study aims one and two was selected from overall sample. Anthropometric, fitness and individual player performance (actual game) data were collected in the subsample. These data were analyzed through clustering methods, ANOVA and independence chi-square test. Then, we investigated whether the proportion of players with the highest individual player performance profile might predict a team's results in the championship. Cluster analysis identified three volleyball fitness profiles (high, medium, and low) and two individual player performance profiles (high and low). The results showed a relationship between both types of profile (fitness and individual player performance). Then, linear regression revealed a moderate relationship between the number of players with a high volleyball fitness profile and a team's results in the championship (R2=0.23). The current study findings may enable coaches and trainers to manage training programs more efficiently in order to obtain tailor-made training, identify volleyball-specific physical fitness training requirements and reach better results during competitions.

  8. A Clinical Score to Predict Appendicitis in Older Male Children.

    Science.gov (United States)

    Kharbanda, Anupam B; Monuteaux, Michael C; Bachur, Richard G; Dudley, Nanette C; Bajaj, Lalit; Stevenson, Michelle D; Macias, Charles G; Mittal, Manoj K; Bennett, Jonathan E; Sinclair, Kelly; Dayan, Peter S

    2017-04-01

    To develop a clinical score to predict appendicitis among older, male children who present to the emergency department with suspected appendicitis. Patients with suspected appendicitis were prospectively enrolled at 9 pediatric emergency departments. A total of 2625 patients enrolled; a subset of 961 male patients, age 8-18 were analyzed in this secondary analysis. Outcomes were determined using pathology, operative reports, and follow-up calls. Clinical and laboratory predictors with  0.4 were entered into a multivariable model. Resultant β-coefficients were used to develop a clinical score. Test performance was assessed by calculating the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios. The mean age was 12.2 years; 49.9% (480) had appendicitis, 22.3% (107) had perforation, and the negative appendectomy rate was 3%. In patients with and without appendicitis, overall imaging rates were 68.6% (329) and 84.4% (406), respectively. Variables retained in the model included maximum tenderness in the right lower quadrant, pain with walking/coughing or hopping, and the absolute neutrophil count. A score ≥8.1 had a sensitivity of 25% (95% confidence interval [CI], 20%-29%), specificity of 98% (95% CI, 96%-99%), and positive predictive value of 93% (95% CI, 86%-97%) for ruling in appendicitis. We developed an accurate scoring system for predicting appendicitis in older boys. If validated, the score might allow clinicians to manage a proportion of male patients without diagnostic imaging. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  9. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  10. Epidemiological and Clinical profile of HIV-infected patients ...

    African Journals Online (AJOL)

    Background: Treatment and care services for HIV patients in Tanzania began 2004 with free access to anti-retroviral therapy (ART). More than 1000 HIV clinics have been established to-date. Each clinic is obliged to provide statistical and clinical feedback for further improvement. Broad objective: The objective of this study ...

  11. Physiotherapy students' perceptions and experiences of clinical prediction rules.

    Science.gov (United States)

    Knox, Grahame M; Snodgrass, Suzanne J; Stanton, Tasha R; Kelly, David H; Vicenzino, Bill; Wand, Benedict M; Rivett, Darren A

    2017-09-01

    Clinical reasoning can be difficult to teach to pre-professional physiotherapy students due to their lack of clinical experience. It may be that tools such as clinical prediction rules (CPRs) could aid the process, but there has been little investigation into their use in physiotherapy clinical education. This study aimed to determine the perceptions and experiences of physiotherapy students regarding CPRs, and whether they are learning about CPRs on clinical placement. Cross-sectional survey using a paper-based questionnaire. Final year pre-professional physiotherapy students (n=371, response rate 77%) from five universities across five states of Australia. Sixty percent of respondents had not heard of CPRs, and a further 19% had not clinically used CPRs. Only 21% reported using CPRs, and of these nearly three-quarters were rarely, if ever, learning about CPRs in the clinical setting. However most of those who used CPRs (78%) believed CPRs assisted in the development of clinical reasoning skills and none (0%) was opposed to the teaching of CPRs to students. The CPRs most commonly recognised and used by students were those for determining the need for an X-ray following injuries to the ankle and foot (67%), and for identifying deep venous thrombosis (63%). The large majority of students in this sample knew little, if anything, about CPRs and few had learned about, experienced or practiced them on clinical placement. However, students who were aware of CPRs found them helpful for their clinical reasoning and were in favour of learning more about them. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  12. The influence of profiled ceilings on sports hall acoustics : Ground effect predictions and scale model measurements

    NARCIS (Netherlands)

    Wattez, Y.C.M.; Tenpierik, M.J.; Nijs, L.

    2018-01-01

    Over the last few years, reverberation times and sound pressure levels have been measured in many sports halls. Most of these halls, for instance those made from stony materials, perform as predicted. However, sports halls constructed with profiled perforated steel roof panels have an unexpected

  13. Profiling healthy eaters: determining factors that predict healthy eating practices among Dutch adults

    NARCIS (Netherlands)

    Swan, E.; Bouwman, L.; Hiddink, G.J.; Aarts, N.; Koelen, M.

    2015-01-01

    Research has identified multiple factors that predict unhealthy eating practices. However what remains poorly understood are factors that promote healthy eating practices. This study aimed to determine a set of factors that represent a profile of healthy eaters. This research applied Antonovsky's

  14. Profiling healthy eaters. Determining factors that predict healthy eating practices among Dutch adults

    NARCIS (Netherlands)

    Swan, E.C.; Bouwman, L.I.; Hiddink, G.J.; Aarts, N.; Koelen, M.

    2015-01-01

    Research has identified multiple factors that predict unhealthy eating practices. However what remains poorly understood are factors that promote healthy eating practices. This study aimed to determine a set of factors that represent a profile of healthy eaters. This research applied Antonovsky's

  15. The use of background and ability profiles to predict college student outcomes.

    Science.gov (United States)

    Schmitt, Neal; Oswald, Frederick L; Kim, Brian H; Imus, Anna; Merritt, Stephanie; Friede, Alyssa; Shivpuri, Smriti

    2007-01-01

    To determine whether profiles of predictor variables provide incremental prediction of college student outcomes, the authors 1st applied an empirical clustering method to profiles based on the scores of 2,771 entering college students on a battery of biographical data and situational judgment measures, along with SAT and American College Test scores and high school grade point average, which resulted in 5 student groups. Performance of the students in these clusters was meaningfully different on a set of external variables, including college grade point average, self-rated performance, class absenteeism, organizational citizenship behavior, intent to quit their university, and satisfaction with college. The 14 variables in the profile were all significantly correlated with 1 or more of the outcome measures; however, nonlinear prediction of these outcomes on the basis of cluster membership did not add incrementally to a linear-regression-based combination of these 14 variables as predictors. 2007 APA, all rights reserved

  16. Temperament profiles of Sasang typology in a child clinical sample

    Directory of Open Access Journals (Sweden)

    Soo Jin Lee

    2012-12-01

    Conclusion: These results demonstrated distinct temperament traits associated with traditional Korean Sasang types in children using an objective biopsychological personality inventory. With further investigation into the biopsychological profiles of the children, the longitudinal stability of the Sasang typology can be examined.

  17. Demographic and clinical profile of patients with juvenile onset open ...

    African Journals Online (AJOL)

    visually impaired at presentation. This obviously has strong socioeconomic implication when the damage resulting from. JOAG is quantified in terms of .... documented was a one-time measurement may not be a total representative of the IOP profile for these patients. Merritt et al.[20] recorded the highest IOP between 6 p.m..

  18. Antibiotic resistance profile of staphylococci from clinical sources ...

    African Journals Online (AJOL)

    Infants, children and the aged are among the groups most vulnerable to microbial infections more so when these microbial agents become resistant to antimicrobials. The antibiotic resistant profile of Staphylococcus aureus and selected coagulase negative staphylococci were determined by standard methods. Of the 178 ...

  19. A protein structural classes prediction method based on predicted secondary structure and PSI-BLAST profile.

    Science.gov (United States)

    Ding, Shuyan; Li, Yan; Shi, Zhuoxing; Yan, Shoujiang

    2014-02-01

    Knowledge of protein secondary structural classes plays an important role in understanding protein folding patterns. In this paper, 25 features based on position-specific scoring matrices are selected to reflect evolutionary information. In combination with other 11 rational features based on predicted protein secondary structure sequences proposed by the previous researchers, a 36-dimensional representation feature vector is presented to predict protein secondary structural classes for low-similarity sequences. ASTRALtraining dataset is used to train and design our method, other three low-similarity datasets ASTRALtest, 25PDB and 1189 are used to test the proposed method. Comparisons with other methods show that our method is effective to predict protein secondary structural classes. Stand alone version of the proposed method (PSSS-PSSM) is written in MATLAB language and it can be downloaded from http://letsgob.com/bioinfo_PSSS_PSSM/. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. High quality protein sequence alignment by combining structural profile prediction and profile alignment using SABER-TOOTH.

    Science.gov (United States)

    Teichert, Florian; Minning, Jonas; Bastolla, Ugo; Porto, Markus

    2010-05-14

    Protein alignments are an essential tool for many bioinformatics analyses. While sequence alignments are accurate for proteins of high sequence similarity, they become unreliable as they approach the so-called 'twilight zone' where sequence similarity gets indistinguishable from random. For such distant pairs, structure alignment is of much better quality. Nevertheless, sequence alignment is the only choice in the majority of cases where structural data is not available. This situation demands development of methods that extend the applicability of accurate sequence alignment to distantly related proteins. We develop a sequence alignment method that combines the prediction of a structural profile based on the protein's sequence with the alignment of that profile using our recently published alignment tool SABERTOOTH. In particular, we predict the contact vector of protein structures using an artificial neural network based on position-specific scoring matrices generated by PSI-BLAST and align these predicted contact vectors. The resulting sequence alignments are assessed using two different tests: First, we assess the alignment quality by measuring the derived structural similarity for cases in which structures are available. In a second test, we quantify the ability of the significance score of the alignments to recognize structural and evolutionary relationships. As a benchmark we use a representative set of the SCOP (structural classification of proteins) database, with similarities ranging from closely related proteins at SCOP family level, to very distantly related proteins at SCOP fold level. Comparing these results with some prominent sequence alignment tools, we find that SABERTOOTH produces sequence alignments of better quality than those of Clustal W, T-Coffee, MUSCLE, and PSI-BLAST. HHpred, one of the most sophisticated and computationally expensive tools available, outperforms our alignment algorithm at family and superfamily levels, while the use of

  1. High quality protein sequence alignment by combining structural profile prediction and profile alignment using SABER-TOOTH

    Directory of Open Access Journals (Sweden)

    Bastolla Ugo

    2010-05-01

    Full Text Available Abstract Background Protein alignments are an essential tool for many bioinformatics analyses. While sequence alignments are accurate for proteins of high sequence similarity, they become unreliable as they approach the so-called 'twilight zone' where sequence similarity gets indistinguishable from random. For such distant pairs, structure alignment is of much better quality. Nevertheless, sequence alignment is the only choice in the majority of cases where structural data is not available. This situation demands development of methods that extend the applicability of accurate sequence alignment to distantly related proteins. Results We develop a sequence alignment method that combines the prediction of a structural profile based on the protein's sequence with the alignment of that profile using our recently published alignment tool SABERTOOTH. In particular, we predict the contact vector of protein structures using an artificial neural network based on position-specific scoring matrices generated by PSI-BLAST and align these predicted contact vectors. The resulting sequence alignments are assessed using two different tests: First, we assess the alignment quality by measuring the derived structural similarity for cases in which structures are available. In a second test, we quantify the ability of the significance score of the alignments to recognize structural and evolutionary relationships. As a benchmark we use a representative set of the SCOP (structural classification of proteins database, with similarities ranging from closely related proteins at SCOP family level, to very distantly related proteins at SCOP fold level. Comparing these results with some prominent sequence alignment tools, we find that SABERTOOTH produces sequence alignments of better quality than those of Clustal W, T-Coffee, MUSCLE, and PSI-BLAST. HHpred, one of the most sophisticated and computationally expensive tools available, outperforms our alignment algorithm at

  2. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

    Directory of Open Access Journals (Sweden)

    Liao Li

    2010-10-01

    Full Text Available Abstract Background Protein-protein interaction (PPI plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs, based on domains represented as interaction profile hidden Markov models (ipHMM where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB. Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD. Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure, an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on

  3. Clinical features and antinuclear antibodies profile among adults with systemic lupus erythematosus and lupus nephritis: a cross-sectional study.

    Science.gov (United States)

    Ahmed, Nashwa; Shigidi, Mazin; Al Agib, Al Nour; Abdelrahman, Hassan; Taha, Elshafie

    2017-01-01

    Limited data is available regarding the clinical manifestations and pattern of Systemic Lupus Erythematosus (SLE) in Sudan. This study aimed to determine the clinical manifestations and Antinuclear Antibodies (ANA) profile among Sudanese adults with SLE and lupus nephritis (LN). A descriptive study was conducted in Omdurman Military Hospital, Sudan. It included all adults with SLE and on regular follow-up during the study period (December 2012 to May 2013). These were investigated regarding their demographic details, clinical features, and immunological profile (ANA, anti-double stranded DNA, and ANA profile 3 levels). Patients with LN had their pattern of renal involvement described; furthermore, associations between the various SLE reactive antibodies and the histological diagnosis of lupus were studied. Sixty-two Sudanese adults with SLE were included, their mean age was 31 ± 10.9 year. Females made 93.5% of patients. A clear predominance of those of Arab ancestry was seen, with most patients being from the Ja'alin and Shaigiya ethnic groups accounting for 29% and 12.9%, respectively. Arthritis was the dominant clinical manifestation seen in 85.5%, whereas renal involvement was seen in 66.1% of patients. Lupus nephritis class III was the dominant histological lesion, seen in 39% of patients. On correlating the ANA profile to the histopathological diagnosis of LN, anti-Nucleosomes and anti-AMA-M2 autoantibodies were found to be significantly associated with LN class IV and class VI, respectively (P values < 0.05). Further epidemiological studies regarding SLE and its ANA profile remain essential as they might help predicting the clinical patterns of the disease and its prognosis.

  4. Murine Cyp3a knockout chimeric mice with humanized liver: prediction of the metabolic profile of nefazodone in humans.

    Science.gov (United States)

    Nakada, Naoyuki; Kawamura, Akio; Kamimura, Hidetaka; Sato, Koya; Kazuki, Yasuhiro; Kakuni, Masakazu; Ohbuchi, Masato; Kato, Kota; Tateno, Chise; Oshimura, Mitsuo; Usui, Takashi

    2016-01-01

    Chimeric mice with humanized livers (PXB mice) are used to investigate the metabolism and pharmacokinetics of drugs in humans. However, residual murine enzymatic activities derived from the liver and the presence of mouse small intestinal metabolism can hamper the prediction of human drug metabolism. Recently murine Cytochrome P450 3a gene knockout chimeric mice with humanized livers (Cyp3a KO CM) were developed. To evaluate the prediction of drug metabolism, nefazodone (NEF) was administered orally at 10 mg/kg to the following mouse strains: Cyp3a KO CM, murine Cyp3a gene knockout (Cyp3a KO), PXB and severe combined immunodeficiency (SCID) mice. Liquid chromatography-mass spectrometry was used for metabolic profiling of plasma, urine and bile. The prediction of human metabolite levels such as hydroxy nefazodone (OH-NEF), triazoledione form (TD), m-chlorophenylpiperazine and dealkyl metabolites in Cyp3a KO CM was superior to that in Cyp3a KO, PXB or SCID mice. Further, clinical exposure levels of NEF, OH-NEF and TD were reproduced in Cyp3a KO CM. In contrast, NEF was rapidly metabolized to TD in both PXB and SCID mice but not in Cyp3a KO mice, suggesting that murine CYP3A is involved in the elimination of NEF in these mice. These findings demonstrate that the metabolic profile of NEF in Cyp3a KO CM differs qualitatively and quantitatively from that in PXB mice due to the higher metabolic rate of NEF and its metabolites via murine CYP3A. Therefore Cyp3a KO CM might be useful in predicting the metabolic profiles of drug candidates in humans. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Host genetics predict clinical deterioration in HCV-related cirrhosis.

    Directory of Open Access Journals (Sweden)

    Lindsay Y King

    Full Text Available Single nucleotide polymorphisms (SNPs in the epidermal growth factor (EGF, rs4444903, patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409 genes, and near the interleukin-28B (IL28B, rs12979860 gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25 after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96-3.35 for 2 unfavorable genotypes and 4.03 (95%CI 2.13-7.62 for unfavorable genotypes for all three loci (Ptrend<0.0001. In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression.

  6. Demographic and clinical profile of patients with juvenile onset open ...

    African Journals Online (AJOL)

    Background: This was a non-comparative, retrospective review of patients diagnosed with juvenile open angle glaucoma (JOAG) in the eye clinic of a tertiary hospital in southwestern Nigeria. Objective: To document the demographic characteristics, clinical features and treatment outcome of the patients diagnosed with ...

  7. Clinical Profile Of Atopic Dermatitis In Benin City, Nigeria | Onunu ...

    African Journals Online (AJOL)

    Objective: To study the clinical presentation and management problems of atopic dermatitis in Benin City, Nigeria. Design: A 15-year retrospective study from May 1985 to April 2000. Setting: Dermatology clinics of the University of Benin Teaching Hospital, Benin City, Nigeria. Subjects: All new cases of atopic dermatitis ...

  8. Protein Profile study of clinical samples using Laser Induced Fluorescence as the detection method

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Raja, Sujatha N.; Rai, Lavanya

    2009-01-01

      Protein profiles of tissue homogenates were recorded using HPLC separation and LIF detection method. The samples were collected from volunteers with clinically normal or cervical cancer conditions. It is shown that the protein profile can be classified as belonging to malignant or normal state ...

  9. Longitudinal prediction and concurrent functioning of adolescent girls demonstrating various profiles of dating violence and victimization.

    Science.gov (United States)

    Chiodo, Debbie; Crooks, Claire V; Wolfe, David A; McIsaac, Caroline; Hughes, Ray; Jaffe, Peter G

    2012-08-01

    Adolescent girls are involved in physical dating violence as both perpetrators and victims, and there are negative consequences associated with each of these behaviors. This article used a prospective design with 519 girls dating in grade 9 to predict profiles of dating violence in grade 11 based on relationships with families of origin (child maltreatment experiences, harsh parenting), and peers (harassment, delinquency, relational aggression). In addition, dating violence profiles were compared on numerous indices of adjustment (school connectedness, grades, self-efficacy and community connectedness) and maladjustment (suicide attempts, distress, delinquency, sexual behavior) for descriptive purposes. The most common profile was no dating violence (n = 367) followed by mutual violence (n = 81). Smaller numbers of girls reported victimization or perpetration only (ns = 39 and 32, respectively). Predicting grade 11 dating violence profile membership from grade 9 relationships was limited, although delinquency, parental rejection, and sexual harassment perpetration predicted membership to the mutually violent group, and delinquency predicted the perpetrator-only group. Compared to the non-violent group, the mutually violent girls in grade 11 had lower grades, poorer self-efficacy, and lower school connectedness and community involvement. Furthermore, they had higher rates of peer aggression and delinquency, were less likely to use condoms and were much more likely to have considered suicide. There were fewer differences among the profiles for girls involved with dating violence. In addition, the victims-only group reported higher rates of sexual intercourse, comparable to the mutually violent group and those involved in nonviolent relationships. Implications for prevention and intervention are highlighted.

  10. Prediction of opioid dose in cancer pain patients using genetic profiling

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Grønlund, Debbie; Gram, Mikkel

    2018-01-01

    OBJECTIVE: Use of opioids for pain management has increased over the past decade; however, inadequate analgesic response is common. Genetic variability may be related to opioid efficacy, but due to the many possible combinations and variables, statistical computations may be difficult. This study...... investigated whether data processing with support vector machine learning could predict required opioid dose in cancer pain patients, using genetic profiling. Eighteen single nucleotide polymorphisms (SNPs) within the µ and δ opioid receptor genes and the catechol-O-methyltransferase gene were selected...... dose using genetic profiling....

  11. Demographic and clinical profile of patients with juvenile onset open ...

    African Journals Online (AJOL)

    Nigerian Journal of Clinical Practice. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 14, No 4 (2011) >. Log in or Register to get access to full text downloads.

  12. Clinical profile of atopic dermatitis in Benin City, Nigeria.

    Science.gov (United States)

    Onunu, A N; Eze, E U; Kubeyinje, E P

    2007-12-01

    To study the clinical presentation and management problems of atopic dermatitis in Benin City, Nigeria. A 15-year retrospective study from May 1985 to April 2000. Dermatology clinics of the University of Benin Teaching Hospital, Benin City, Nigeria. All new cases of atopic dermatitis presenting to the clinic during the study period. 594 patients suffering from atopic dermatitis, representing 7.92% of new dermatological cases were seen during the study period. There was a slight male preponderance; the male to female ratio was 1.2: 1. Most patients were below 30 years of age with the peak incidence in the 0 9-year age group, with most presenting in the first six months of life. Forty-six percent of the patients had a positive family history of atopy, while 73% also had other atopic disorders. The clinical patterns seen were infantile, childhood and adult forms, which is in keeping with reports from other parts of the world. Precipitating factors were most often obscure; however, high temperatures and humidity were the most common aggravating factors. The important problems encountered were misuse of topical medications, oral antibiotics, anti-fungal drugs and a high follow-up default rate. The clinical characteristics of atopic dermatitis in our study population were similar to the pattern in other parts of the world. There is need for increased awareness of its importance as a cause of morbidity especially in children.

  13. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    Science.gov (United States)

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. © The Author(s) 2015.

  14. Single-cell genomic profiling of acute myeloid leukemia for clinical use: A pilot study.

    Science.gov (United States)

    Yan, Benedict; Hu, Yongli; Ban, Kenneth H K; Tiang, Zenia; Ng, Christopher; Lee, Joanne; Tan, Wilson; Chiu, Lily; Tan, Tin Wee; Seah, Elaine; Ng, Chin Hin; Chng, Wee-Joo; Foo, Roger

    2017-03-01

    Although bulk high-throughput genomic profiling studies have led to a significant increase in the understanding of cancer biology, there is increasing awareness that bulk profiling approaches do not completely elucidate tumor heterogeneity. Single-cell genomic profiling enables the distinction of tumor heterogeneity, and may improve clinical diagnosis through the identification and characterization of putative subclonal populations. In the present study, the challenges associated with a single-cell genomics profiling workflow for clinical diagnostics were investigated. Single-cell RNA-sequencing (RNA-seq) was performed on 20 cells from an acute myeloid leukemia bone marrow sample. Putative blasts were identified based on their gene expression profiles and principal component analysis was performed to identify outlier cells. Variant calling was performed on the single-cell RNA-seq data. The present pilot study demonstrates a proof of concept for clinical single-cell genomic profiling. The recognized limitations include significant stochastic RNA loss and the relatively low throughput of the current proposed platform. Although the results of the present study are promising, further technological advances and protocol optimization are necessary for single-cell genomic profiling to be clinically viable.

  15. Theoretical prediction of Reynolds stresses and velocity profiles for barotropic turbulent jets

    Science.gov (United States)

    Woillez, E.; Bouchet, F.

    2017-06-01

    It is extremely uncommon to be able to predict the velocity profile of a turbulent flow. In two-dimensional flows, atmosphere dynamics, and plasma physics, large-scale coherent jets are created through inverse energy transfers from small scales to the largest scales of the flow. We prove that in the limits of vanishing energy injection, vanishing friction, and small-scale forcing, the velocity profile of a jet obeys an equation independently of the details of the forcing. We find another general relation for the maximal curvature of a jet and we give strong arguments to support the existence of a hydrodynamic instability at the point with minimal jet velocity. Those results are the first computations of Reynolds stresses and self-consistent velocity profiles from the turbulent dynamics, and the first consistent analytic theory of zonal jets in barotropic turbulence.

  16. Prediction of metastasis from low-malignant breast cancer by gene expression profiling

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Eiriksdottir, Freyja

    2007-01-01

    examined in these studies is the low-risk patients for whom outcome is very difficult to predict with currently used methods. These patients do not receive adjuvant treatment according to the guidelines of the Danish Breast Cancer Cooperative Group (DBCG). In this study, 26 tumors from low-risk patients......Promising results for prediction of outcome in breast cancer have been obtained by genome wide gene expression profiling. Some studies have suggested that an extensive overtreatment of breast cancer patients might be reduced by risk assessment with gene expression profiling. A patient group hardly...... and 77% specificity. The classifier was also validated in an independent group of high-risk tumors resulting in comparable performance of HUMAC32 and a 70-gene classifier developed for this group. Furthermore, the 70-gene signature was tested in our low- and intermediate-risk samples. The results...

  17. HMMBinder: DNA-Binding Protein Prediction Using HMM Profile Based Features

    Directory of Open Access Journals (Sweden)

    Rianon Zaman

    2017-01-01

    Full Text Available DNA-binding proteins often play important role in various processes within the cell. Over the last decade, a wide range of classification algorithms and feature extraction techniques have been used to solve this problem. In this paper, we propose a novel DNA-binding protein prediction method called HMMBinder. HMMBinder uses monogram and bigram features extracted from the HMM profiles of the protein sequences. To the best of our knowledge, this is the first application of HMM profile based features for the DNA-binding protein prediction problem. We applied Support Vector Machines (SVM as a classification technique in HMMBinder. Our method was tested on standard benchmark datasets. We experimentally show that our method outperforms the state-of-the-art methods found in the literature.

  18. Prediction of crank torque and pedal angle profiles during pedaling movements by biomechanical optimization

    DEFF Research Database (Denmark)

    Farahani, Saeed Davoudabadi; Bertucci, William; Andersen, Michael Skipper

    2015-01-01

    and constraints. The cost function and the constraints typically express performance, comfort, injury risk, fatigue, muscle load, joint forces and other physiological properties derived from the detailed musculoskeletal analysis. A physiology-based cost function that expresses the integral effort over a cycle...... to predict the motion pattern and crank torque was used. An experiment was conducted on a group of eight highly trained male cyclists to compare experimental observations to the simulation results. The proposed performance criterion predicts realistic crank torque profiles and ankle movement patterns....

  19. Predicting pressure ulcers: cases missed using a new clinical prediction rule.

    Science.gov (United States)

    Schoonhoven, Lisette; Grobbee, Diederick E; Bousema, Mente T; Buskens, Erik

    2005-01-01

    The aim of this paper is to report a study describing patients with pressure ulcers that were incorrectly classified as 'not at risk' by the prediction rule and comparing them with patients who were correctly classified as 'not at risk'. Patients admitted to hospital are at risk of developing pressure ulcers. Although the majority of pressure ulcers can be predicted using a recently developed prediction rule, up to 30% of patients with pressure ulcers may still be misclassified. Between January 1999 and June 2000 a prospective cohort study was conducted in two large hospitals in the Netherlands. Patients admitted to neurology, internal, surgical, and elder care wards for more than 5 days were included (n = 1229), and were examined weekly. Information on potential prognostic determinants for pressure ulcers mentioned in the literature was recorded. Outcome was defined as occurrence of a pressure ulcer grade 2 or worse during hospital admission. Patients who developed pressure ulcers experienced more problems with 'friction and shear' and underwent surgery more often and longer. Also, they were more often admitted because of malignant conditions. We found no specific characteristics that clearly distinguished patients with pressure ulcers that were incorrectly classified as 'not at risk' by the prediction rule from patients who were correctly classified as 'not at risk'. It appears difficult to improve further on the prediction of pressure ulcers using available clinical information.

  20. Assessing predicted HIV-1 replicative capacity in a clinical setting.

    Directory of Open Access Journals (Sweden)

    Roger D Kouyos

    2011-11-01

    Full Text Available HIV-1 replicative capacity (RC provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load.

  1. Ozone Mapping and Profiler Suite: using mission performance data to refine predictive contamination modeling

    Science.gov (United States)

    Devaud, Genevieve; Jaross, Glen

    2014-09-01

    On October 28, 2011, the Suomi National Polar-orbiting Partnership (Suomi NPP) satellite launched at Vandenberg Air Force base aboard a United Launch Alliance Delta II rocket. Included among the five instruments was the Ozone Mapping and Profiler Suite (OMPS), an advanced suite of three hyperspectral instruments built by Ball Aerospace and Technologies Corporation (BATC) for the NASA Goddard Space Flight Center. Molecular transport modeling is used to predict optical throughput changes due to contaminant accumulation to ensure performance margin to End Of Life. The OMPS Nadir Profiler, operating at the lowest wavelengths of 250 - 310 nm, is most sensitive to contaminant accumulation. Geometry, thermal profile and material properties must be accurately modeled in order to have confidence in the results, yet it is well known that the complex chemistry and process dependent variability of aerospace materials presents a substantial challenge to the modeler. Assumptions about the absorption coefficients, desorption and diffusion kinetics of outgassing species from polymeric materials dramatically affect the model predictions, yet it is rare indeed that on-mission data is analyzed at a later date as a means to compare with modeling results. Optical throughput measurements for the Ozone and Mapping Profiler Suite on the Suomi NPP Satellite indicate that optical throughput degradation between day 145 and day 858 is less than 0.5%. We will show how assumptions about outgassing rates and desorption energies, in particular, dramatically affect the modeled optical throughput and what assumptions represent the on-orbit data.

  2. Nasal polyps - clinical profile and management in Ibadan, Nigeria ...

    African Journals Online (AJOL)

    Background: Nasal polyps are benign mucosal protrusions into the nasal cavity of multifactorial origin and are characterized by chronic mucosal inflammation. They result from the prolapsed lining of the ethmoid sinuses and block the nose to a variable degree depending on their sizes. This study aims to evaluate the clinical ...

  3. Clinical Profile and HIV/AIDS Prevalence of Patients with ...

    African Journals Online (AJOL)

    Females made up 59%, with a male: female ratio 1:1.4. The common clinical features were weight loss (62.0%), glandular body swellings (28.0%) and prolonged fever (25.0%). Persistent fever >1month, weight loss >10% body weight and unexplained diarrhoea >1month were present in 66.7%, 83.3% and 16.7% HIV ...

  4. Plasma Homocysteine Level and its Relationship to Clinical Profile ...

    African Journals Online (AJOL)

    Background: Hyperhomocysteinaemia (HHcy) is as a longterm sequelum of levodopa therapy in Parkinson's disease (PD). Information on its frequency and effects in Africans with PD is sparse. Objective: To determine the frequency of HHcy and its relationship to clinical features of PD in African patients. Methods: Using a ...

  5. Clinical Profile of Unilateral Proptosis in a Tertiary Care Centre

    Directory of Open Access Journals (Sweden)

    Susan Dsouza

    2017-01-01

    Full Text Available Proptosis, the forward protrusion of the eyeball, is a common manifestation of a wide variety of diseases inside the orbit and its spaces. Its diagnosis is usually a combined effort of the ophthalmologist, otolaryngologist, neurosurgeon, and radiologist. A clinical study of twenty-five cases with unilateral proptosis were studied in different age groups over a period of about 3 years under different headings like distribution, clinical features, radiological features, histopathological aspects, management, and outcomes of diseases. Proptosis measurement was done by simple/plastic ruler exophthalmometry, and diagnosis was made after a detailed clinical examination and ancillary tests. Treatment modality was decided based on radiological and histopathological examination reports, which included medical surgery, radiotherapy, and chemotherapy or a combination of all. In our study, most of the patients were in the age group of more than 60 years. The M : F ratio is 3 : 1. One case had a large proptosis of 18 mm above normal and 2 cases were as small as 3 mm. Diagnosis was mainly done by clinical features and confirmed by radiological and histopathological features. Most of them were treated medically (13 cases, i.e., 52% and the rest by surgery with a combination of radiotherapy/chemotherapy (12 cases, i.e., 48%.

  6. Clinical profile of neurological complications in HIV- reactive ...

    African Journals Online (AJOL)

    McRoy

    2014-07-26

    Jul 26, 2014 ... radiculopathy. Though three patients of these four were already taking anti- retroviral drugs, neuropathy in them could not be attributed to these drugs. Tingling, sensory loss, lower limb distal muscle weakness, backache and imbalance were the clinical features noted. In the present study, HIV-associated.

  7. Demographic and clinical profile of patients with juvenile onset open ...

    African Journals Online (AJOL)

    with fatalistic beliefs such as withcraft ranking highest in the cause of blindness. All these factors might have contributed to the late presentation among these patients. The high clinic dropout rate of 26.7% is a cause for much concern. This could be a reflection of the way the patients perceived their eye problem. In a review ...

  8. clinical profile of atopic dermatitis in benin city, nigeria.

    African Journals Online (AJOL)

    encountered were misuse 'of topical medications, oral antibiotics, anti-fungal drugs and a high follow-up default rate. Conclusion: The clinical characteristics of atopic dermatitis in our study population were similar to the pattern in other parts of the world. There is need for increased awareness of its importance as a cause of ...

  9. Profile and management of patients at a memory clinic | Kalula ...

    African Journals Online (AJOL)

    In this connection, the University of Cape Town/Groote Schuur Hospital (UCT/ GSH) Memory Clinic provides a valuable service to patients, families and health professionals. High levels of behavioural and psychological symptoms of dementia need expert tertiary level assessment and management. Public education on ...

  10. Is Dental Students' Clinical Productivity Associated with Their Personality Profile?

    Science.gov (United States)

    Rodriguez, Kristan D; Bartoloni, Joseph A; Hendricson, William D

    2017-12-01

    The aim of this study was to assess the relationship between personality preferences of incoming fourth-year dental students at the University of Texas Health Science Center at San Antonio as measured by the Keirsey Temperament Sorter II and their third-year clinical productivity and percentage of broken appointments. All 105 incoming fourth-year dental students in 2016 were invited to participate in the study, and 92 students completed the temperament questionnaire, for a response rate of 87.5%. Those students' clinical activity during their third year was measured by production points and percentage of broken appointments extracted from the electronic health record. The results showed that the majority of the respondents were extroverts rather than introverts and that the extroverts had significantly higher production points and significantly fewer broken appointments than the introverts. The most common personality preferences were sensing and judging. More than two-thirds of the respondents represented the Guardian temperament, one of four categories on the temperament measure. These findings help highlight the traits that may contribute to success in clinical training during dental school and support the notion that clinical success may be influenced by certain personality characteristics as well as the technical and specialized skills of dentistry.

  11. Profile of clinically-diagnosed dementias in a neuropsychiatric ...

    African Journals Online (AJOL)

    Lund and Manchester Criteria for Frontotemporal dementia. (FTD)20 and the Clinical Diagnostic criteria for Parkinson disease Dementia (PDD)21 were utilized. The ICD-10 criteria included cognitive impairment in a conscious and alert state, functional and physical impairment resulting from above, persistence of symptoms ...

  12. Haematological and clinical profile in Nigerian sickle cell disease ...

    African Journals Online (AJOL)

    Results: The crises frequency and transfusion history (in males) together with the corrected reticulocyte count (in females) were significantly different in SCD patients with CKD, compared to those without (p values<0.05). Conclusion: Kidney disease significantly influences some clinical and haematological parameters in ...

  13. ORIGINAL ARTICLES Clinical profile and predictors of severe ...

    African Journals Online (AJOL)

    2008-10-16

    Oct 16, 2008 ... Severe infections, especially sepsis and pneumonia, account for 36% of these deaths,6 prematurity for 28% and ... the utility of previously proposed clinical signs and symptoms for identifying severe illness in young infants of 0 - 59 days ... evaluation and treatment. Enrolment took place on Monday to Friday ...

  14. Clinical neuroprediction: Amygdala reactivity predicts depressive symptoms 2 years later.

    Science.gov (United States)

    Mattson, Whitney I; Hyde, Luke W; Shaw, Daniel S; Forbes, Erika E; Monk, Christopher S

    2016-06-01

    Depression is linked to increased amygdala activation to neutral and negatively valenced facial expressions. Amygdala activation may be predictive of changes in depressive symptoms over time. However, most studies in this area have focused on small, predominantly female and homogenous clinical samples. Studies are needed to examine how amygdala reactivity relates to the course of depressive symptoms dimensionally, prospectively and in populations diverse in gender, race and socioeconomic status. A total of 156 men from predominately low-income backgrounds completed an fMRI task where they viewed emotional facial expressions. Left and right amygdala reactivity to neutral, but not angry or fearful, facial expressions relative to a non-face baseline at age 20 predicted greater depressive symptoms 2 years later, controlling for age 20 depressive symptoms. Heightened bilateral amygdala reactivity to neutral facial expressions predicted increases in depressive symptoms 2 years later in a large community sample. Neutral facial expressions are affectively ambiguous and a tendency to interpret these stimuli negatively may reflect to cognitive biases that lead to increases in depressive symptoms over time. Individual differences in amygdala reactivity to neutral facial expressions appear to identify those at most risk for a more problematic course of depressive symptoms across time. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Cellular imaging predictions of clinical drug-induced liver injury.

    Science.gov (United States)

    Xu, Jinghai J; Henstock, Peter V; Dunn, Margaret C; Smith, Arthur R; Chabot, Jeffrey R; de Graaf, David

    2008-09-01

    Drug-induced liver injury (DILI) is the most common adverse event causing drug nonapprovals and drug withdrawals. Using drugs as test agents and measuring a panel of cellular phenotypes that are directly linked to key mechanisms of hepatotoxicity, we have developed an in vitro testing strategy that is predictive of many clinical outcomes of DILI. Mitochondrial damage, oxidative stress, and intracellular glutathione, all measured by high content cellular imaging in primary human hepatocyte cultures, are the three most important features contributing to the hepatotoxicity prediction. When applied to over 300 drugs and chemicals including many that caused rare and idiosyncratic liver toxicity in humans, our testing strategy has a true-positive rate of 50-60% and an exceptionally low false-positive rate of 0-5%. These in vitro predictions can augment the performance of the combined traditional preclinical animal tests by identifying idiosyncratic human hepatotoxicants such as nimesulide, telithromycin, nefazodone, troglitazone, tetracycline, sulindac, zileuton, labetalol, diclofenac, chlorzoxazone, dantrolene, and many others. Our findings provide insight to key DILI mechanisms, and suggest a new approach in hepatotoxicity testing of pharmaceuticals.

  16. Clinical and laboratory profile of patients with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Phelipe Gabriel dos Santos Sant'Ana

    Full Text Available Abstract Objective: This study aimed to describe and analyze clinical and laboratory characteristics of patients with sickle cell anemia treated at the Hemominas Foundation, in Divinópolis, Brazil. Furthermore, this study aimed to compare the clinical and laboratory outcomes of the group of patients treated with hydroxyurea with those patients that were not treated with hydroxyurea. Methods: Clinical and laboratorial data were obtained by analyzing medical records of patients with sickle cell anemia. Results: Data from the medical records of 50 patients were analyzed. Most of the patients were female (56%, aged between 20 and 29 years old. Infections, transfusions, cholecystectomy, splenectomy and systemic arterial hypertension were the most common clinical adverse events of the patients. The most frequent cause of hospitalization was painful crisis. The majority of patients had reduced values of hemoglobin and hematocrit (8.55 ± 1.33 g/dL and 25.7 ± 4.4%, respectively and increased fetal hemoglobin levels (12 ± 7%. None of the clinical variables was statistically significant on comparing the two groups of patients. Among hematological variables only hemoglobin and hematocrit levels were statistically different between patients treated with hydroxyurea and untreated patients (p-value = 0.005 and p-value = 0.001, respectively. Conclusion: Sickle cell anemia requires treatment and follow-up by a multiprofessional team. A current therapeutic option is hydroxyurea. This drug reduces complications and improves laboratorial parameters of patients. In this study, the use of the drug increased the hemoglobin and hematocrit levels of patients.

  17. Presurgical symptom profiles predict quality of life 2 years after surgery in women with breast cancer.

    Science.gov (United States)

    Chen, Mei-Ling; Liu, Li-Ni; Miaskowski, Christine; Chen, Shin-Cheh; Lin, Yung-Chang; Wang, Jong-Shyan

    2016-01-01

    Higher symptom burden in oncology patients is associated with poorer quality of life (QOL). However, the long-term predictive relationship between pre-treatment symptom profiles and QOL is unknown. The aim of this study was to identify subgroups of breast cancer patients based on their presurgical symptom profiles and to examine the predictive effect of group membership on QOL 2 years after surgery. Data were analyzed from a longitudinal study of women's (N = 198) symptoms after breast cancer surgery. Patient subgroups were identified by latent class analysis based on presurgical severity of five symptoms (i.e., attentional and physical fatigue, sleep disturbance, depression, and anxiety). Among these 198 women, quality of life 2 years after surgery was available for 97. Group differences in QOL were examined by general linear models. We identified four distinct patient groups. Group A (All Low) had low levels of all symptoms. Group B (Low Fatigue and Moderate Mood) was characterized by low attentional and physical fatigue but moderate sleep disturbance, depression, and anxiety. Group C (All Moderate) was characterized by moderate levels of all five symptoms. Group D was characterized by moderate attentional and physical fatigue and severe sleep disturbance, depression, and anxiety (Moderate Fatigue and High Mood). Group D had significantly lower overall QOL scores 2 years after surgery than Group A (p = 0.002). Breast cancer patients' presurgical symptom profile had a long-term predictive effect on QOL. Routine assessment of patients' pre-treatment symptom is suggested to identify high risk group.

  18. Clinical utility of serum biochemical variables for predicting acid-base balance in critically ill horses.

    Science.gov (United States)

    Stämpfli, Henry R; Schoster, Angelika; Constable, Peter D

    2014-12-01

    Profiles from serum biochemical analyzers include the concentration of strong electrolytes (including l-lactate), total carbon dioxide (tCO2 ), and total protein. These variables are associated with changes in acid-base balance. Application of physicochemical principles may allow predicting acid-base balance from serum biochemistry without measuring whole blood pH and pCO2 . The purpose of the study was to determine if the acid-base status of critically ill horses could be accurately predicted using variables included in standard serum biochemical profiles. Two jugular venous blood samples were prospectively obtained from critically ill horses and foals. Samples were analyzed using a whole blood gas and pH analyzer (BG) and a serum biochemistry multi analyzer system (AMAS). Linear regression, Deming regression, and Bland-Altman plots were used for method comparison and P acid base interpretation, were different between the AMAS and BG analyzer. Using physicochemical principles, BG results accurately predicted pH, whereas the AMAS results did not when a fixed value for pCO2 was used. Measurement of pCO2 is required in critically ill horses for accurate prediction of whole blood pH. Differences in the measured values of Na and Cl concentration exist when measured in serum by the AMAS and in whole blood or plasma by BG, indicating that the accurate prediction of whole blood pH is analyzer-dependent. Application of physicochemical principles to plasma or serum provides a practical method to evaluate analyzer accuracy. © 2014 American Society for Veterinary Clinical Pathology.

  19. Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

    Science.gov (United States)

    Velasco, Cesar; Pérez, Inaki; Podzamczer, Daniel; Llibre, Josep Maria; Domingo, Pere; González-García, Juan; Puig, Inma; Ayala, Pilar; Martín, Mayte; Trilla, Antoni; Lázaro, Pablo; Gatell, Josep Maria

    2016-03-01

    The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Impact of INTERMACS Profile on Clinical Outcomes for Patients Supported With the Total Artificial Heart.

    Science.gov (United States)

    Shah, Keyur B; Thanavaro, Kristin L; Tang, Daniel G; Quader, Mohammed A; Mankad, Anit K; Tchoukina, Inna; Thacker, Leroy R; Smallfield, Melissa C; Katlaps, Gundars; Hess, Michael L; Cooke, Richard H; Kasirajan, Vigneshwar

    2016-11-01

    Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients with the total artificial heart (TAH). We studied 66 consecutive patients implanted with the TAH at our institution from 2006 through 2012 and compared outcome by INTERMACS profile. INTERMACS profiles were adjudicated retrospectively by a reviewer blinded to clinical outcomes. Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. INTERMACS profile 1 patients had decreased 6-month survival on the device compared with those in profiles 2-4 (74% vs 95%, log rank: P = .015). For the 50 patients surviving to heart transplantation, the 1-year posttransplant survival was 82%. There was no difference in 1-year survival when comparing patients in the INTERMACS 1 profile with less severe profiles (79% vs 84%; log rank test P = .7; hazard ratio [confidence interval] 1.3 [0.3-4.8]). Patients implanted with the TAH as INTERMACS profile 1 had reduced survival to transplantation compared with less sick profiles. INTERMACS profile at the time of TAH implantation did not affect 1-year survival after heart transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Latent profiles of nonresidential father engagement six years after divorce predict long-term offspring outcomes.

    Science.gov (United States)

    Modecki, Kathryn Lynn; Hagan, Melissa J; Sandler, Irwin; Wolchik, Sharlene A

    2015-01-01

    This study examined profiles of nonresidential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) 6 to 8 years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, 9 years later. Parental divorce occurred during late childhood to early adolescence; indicators of nonresidential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed 9 years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes 9 years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother's remarriage, mother's income, and gender, age, and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems 9 years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long term. Implications of findings for policy and intervention are discussed.

  2. Profile of special needs patients at a pediatric dentistry clinic

    OpenAIRE

    Sílvio Augusto Fernandes de Menezes; Helder Henrique Costa Pinheiro; Luciana Teixeira Passos; Camila de Almeida Smith; Tatiany Oliveira de Alencar Menezes

    2011-01-01

    Objective: To assess the characteristics of special needs patients assisted at the Clinic of Pediatric Dentistry, Faculty of Dentistry, Federal University of Pará. Methods: A descriptive observational study conducted from March 2007 to December 2009, assessing 137 records of which were extracted the following data: gender, age, origin, current and past medical history, type of special needs and major oral diseases. We applied descriptive statistics, one-dimensional frequency table and prepare...

  3. Sleep-wake profiles predict longitudinal changes in manic symptoms and memory in young people with mood disorders.

    Science.gov (United States)

    Robillard, Rébecca; Hermens, Daniel F; Lee, Rico S C; Jones, Andrew; Carpenter, Joanne S; White, Django; Naismith, Sharon L; Southan, James; Whitwell, Bradley; Scott, Elizabeth M; Hickie, Ian B

    2016-10-01

    Mood disorders are characterized by disabling symptoms and cognitive difficulties which may vary in intensity throughout the course of the illness. Sleep-wake cycles and circadian rhythms influence emotional regulation and cognitive functions. However, the relationships between the sleep-wake disturbances experienced commonly by people with mood disorders and the longitudinal changes in their clinical and cognitive profile are not well characterized. This study investigated associations between initial sleep-wake patterns and longitudinal changes in mood symptoms and cognitive functions in 50 young people (aged 13-33 years) with depression or bipolar disorder. Data were based on actigraphy monitoring conducted over approximately 2 weeks and clinical and neuropsychological assessment. As part of a longitudinal cohort study, these assessments were repeated after a mean follow-up interval of 18.9 months. No significant differences in longitudinal clinical changes were found between the participants with depression and those with bipolar disorder. Lower sleep efficiency was predictive of longitudinal worsening in manic symptoms (P = 0.007). Shorter total sleep time (P = 0.043) and poorer circadian rhythmicity (P = 0.045) were predictive of worsening in verbal memory. These findings suggest that some sleep-wake and circadian disturbances in young people with mood disorders may be associated with less favourable longitudinal outcomes, notably for subsequent manic symptoms and memory difficulties. © 2016 European Sleep Research Society.

  4. [Factors predicting sensory profile of 4 to 18 month old infants].

    Science.gov (United States)

    Pedrosa, Carina; Caçola, Priscila; Carvalhal, Maria Isabel Martins Mourão

    2015-01-01

    To identify environment factors predicting sensory profile of infants between 4 and 18 months old. This cross-sectional study evaluated 97 infants (40 females e 57 males), with a mean age of 1.05±0.32 years with the Test of Sensory Functions in Infants (TSFI) and also asked 97 parents and 11 kindergarten teachers of seven daycare centers to answer the Affordances in the Home Environment for Motor Development- Infant Scale (AHEMD-IS). The AHEMD-IS is a questionnaire that characterizes the opportunities in the home environment for infants between 3 and 18 months of age. We tested the association between affordances and the sensory profile of infants. Significant variables were entered into a regression model to determine predictors of sensory profile. The majority of infants (66%) had a normal sensory profile and 34% were at risk or deficit. Affordances in the home were classified as adequate and they were good in the studied daycare centers. The results of the regression revealed that only daily hours in daycare center and daycare outside space influenced the sensory profile of infants, in particular the Ocular-Motor Control component. The sensory profile of infants was between normal and at risk. While the family home offered adequate affordances for motor development, the daycare centers of the infants involved demonstrated a good quantity and quality of affordances. Overall, we conclude that daily hours in the daycare center and daycare outside space were predictors of the sensory profile, particular on Ocular-Motor Control component. Copyright © 2015 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  5. Factors predicting sensory profile of 4 to 18 month old infants

    Science.gov (United States)

    Pedrosa, Carina; Caçola, Priscila; Carvalhal, Maria Isabel Martins Mourão

    2015-01-01

    OBJECTIVE: To identify environment factors predicting sensory profile of infants between 4 and 18 months old. METHODS: This cross-sectional study evaluated 97 infants (40 females e 57 males), with a mean age of 1.05±0.32 years with the Test of Sensory Functions in Infants (TSFI) and also asked 97 parents and 11 kindergarten teachers of seven daycare centers to answer the Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS). The AHEMD-IS is a questionnaire that characterizes the opportunities in the home environment for infants between 3 and 18 months of age. We tested the association between affordances and the sensory profile of infants. Significant variables were entered into a regression model to determine predictors of sensory profile. RESULTS: The majority of infants (66%) had a normal sensory profile and 34% were at risk or deficit. Affordances in the home were classified as adequate and they were good in the studied daycare centers. The results of the regression revealed that only daily hours in daycare center and daycare outside space influenced the sensory profile of infants, in particular the Ocular-Motor Control component. CONCLUSIONS: The sensory profile of infants was between normal and at risk. While the family home offered adequate affordances for motor development, the daycare centers of the infants involved demonstrated a good quantity and quality of affordances. Overall, we conclude that daily hours in the daycare center and daycare outside space were predictors of the sensory profile, particular on Ocular-Motor Control component. PMID:25887929

  6. Factors predicting sensory profile of 4 to 18 month old infants

    Directory of Open Access Journals (Sweden)

    Carina Pedrosa

    2015-06-01

    Full Text Available OBJECTIVE: To identify environment factors predicting sensory profile of infants between 4 and 18 months old. METHODS: This cross-sectional study evaluated 97 infants (40 females e 57 males, with a mean age of 1.05±0.32 years with the Test of Sensory Functions in Infants (TSFI and also asked 97 parents and 11 kindergarten teachers of seven daycare centers to answer the Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS. The AHEMD-IS is a questionnaire that characterizes the opportunities in the home environment for infants between 3 and 18 months of age. We tested the association between affordances and the sensory profile of infants. Significant variables were entered into a regression model to determine predictors of sensory profile. RESULTS: The majority of infants (66% had a normal sensory profile and 34% were at risk or deficit. Affordances in the home were classified as adequate and they were good in the studied daycare centers. The results of the regression revealed that only daily hours in daycare center and daycare outside space influenced the sensory profile of infants, in particular the Ocular-Motor Control component. CONCLUSIONS: The sensory profile of infants was between normal and at risk. While the family home offered adequate affordances for motor development, the daycare centers of the infants involved demonstrated a good quantity and quality of affordances. Overall, we conclude that daily hours in the daycare center and daycare outside space were predictors of the sensory profile, particular on Ocular-Motor Control component.

  7. [Clinical profile of the new antiarrhythmic drug dronedarone].

    Science.gov (United States)

    Schmitt, J; Lewalter, T; Pittrow, D; Duray, G; Goette, A; Brachmann, J; Hohnloser, S H

    2010-03-01

    The new antiarrhythmic drug dronedarone (SR 33 589) is a benzofuran derivative structurally similar to amiodarone, however is noniodinated. The additional methansulfonylgroup renders it less lipophilic, with a substantially shorter half-life, compared to the parent compound. The electrophysiological properties of both agents are similar with inhibition of Na+, K+, and Ca++ currents (all Vaughan-Williams classes). The agent has been evaluated in a large clinical study program. The daily dose of dronedarone 800 mg has been shown (DAFNE) to be effective and well tolerated. In two design-identical randomised clinical trials (EURIDIS and ADONIS trial) the efficacy of dronedarone to maintain sinus rhythm in patients with chronic atrial fibrillation/flutter was shown to be clearly superior to placebo. The ERATO study showed the rate control properties of dronedarone. In the ATHENA morbidity/mortality study, the combined endpoint death or hospitalisation due to cardiovascular events occurred significantly less often in the dronedarone group compared to the placebo group. Particularly due to its beneficial effects on clinical outcomes such as cardiovascular hospitalizations and death in the context of high tolerability dronedarone appears to be a promising new antiarrhythmic compound. Georg Thieme Verlag KG Stuttgart New York.

  8. Clinical Profile, Maternal and Fetal Outcomes of Acute Hepatitis E in ...

    African Journals Online (AJOL)

    obstetric and fetal outcomes. Hence, this study was undertaken to study clinical profile of hepatitis E infection in pregnancy, to evaluate the maternal and fetal complications of this infection and to compare the clinical features of hepatitis E in pregnant women to those in non-pregnant women. Subjects and Methods. This was ...

  9. Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry

    NARCIS (Netherlands)

    Gerritsen, M. G.; Brinkman, P.; Escobar, N.; Bos, L. D.; de Heer, K.; Meijer, M.; Janssen, H.-G.; de Cock, H.; Wösten, H. A. B.; Visser, C. E.; van Oers, M. H. J.; Sterk, P. J.

    2017-01-01

    Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a

  10. Association between obesity and asthma - epidemiology, pathophysiology and clinical profile.

    Science.gov (United States)

    Muc, Magdalena; Mota-Pinto, Anabela; Padez, Cristina

    2016-12-01

    Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms. Nevertheless, prenatal origins of both conditions complicate the search for causality. There is a confirmed role of neuro-immune cross-talk mediating obesity-induced asthma, with leptin playing a key role in these processes. Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it is one of the most important determinants of asthma phenotypes. Two main subphenotypes have been distinguished. The first phenotype, which affects adult women, is characterised by later onset and is more likely to be non-atopic. The childhood obesity-induced asthma phenotype is characterised by primary and predominantly atopic asthma. In obesity-induced asthma, the immune responses are shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2 immunological profile. Moreover, obese asthmatics might respond differently to environmental triggers. The high cost of treatment of obesity-related asthma, and the burden it causes for the patients and their families call for urgent intervention. Phenotype-specific approaches seem to be crucial for the success of prevention and treatment.

  11. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer.

    Science.gov (United States)

    Tramm, Trine; Kyndi, Marianne; Myhre, Simen; Nord, Silje; Alsner, Jan; Sørensen, Flemming Brandt; Sørlie, Therese; Overgaard, Jens

    2014-10-01

    Breast cancer is characterized by great molecular heterogeneity demonstrated, e.g. by the intrinsic subtypes. Administration of post-mastectomy radiotherapy (PMRT) does, however, not reflect this heterogeneity. A gene profile (DBCG-RT profile) has recently been developed and validated, and has shown prognostic impact in terms of loco-regional failure and predictive impact for PMRT. Reports have also shown predictive value in terms of benefit of PMRT from intrinsic subtypes and derived approximations. The aim of this study was to examine: 1) the agreement between various methods for determining the intrinsic subtypes; and 2) the relationship between the prognostic and predictive impact of the DBCG-RT profile and the intrinsic subtypes. Intrinsic subtypes and the DBCG-RT profile was determined from microarray analysis based on fresh frozen tissue from 191 patients included in the Danish Breast Cancer Cooperative Group (DBCG) 82bc trial. Corresponding formalin-fixed, paraffin-embedded tissue was available from 146 of these patients and from another 890 DBCG82bc patients. Estrogen receptor, progesterone receptor, HER2, CK5/6, Ki-67 and EGFR were combined into immunohistochemical approximations of the intrinsic subtypes. Endpoint considered was loco-regional recurrence (LRR). The DBCG-RT profile identified a group of patients with low risk of LRR and no additional benefit from PMRT among all subtypes. Combining six immunohistochemical markers identified a subgroup of triple negative patients with high risk of LRR and significant benefit from PMRT. Agreement in the different assignments of tumors to the subtypes was suboptimal, and the clinical outcome and predicted benefit from PMRT varied according to the method used for assignment. The prognostic and predictive information obtained from the DBCG-RT profile cannot be substituted by any approximation of the tumors intrinsic subtype. The predictive value of the intrinsic subtypes in terms of PMRT was influenced by the

  12. Predictive Clinical Rule for Readmissions in OPAT. Improving in Security

    Science.gov (United States)

    Bengoetxea, Itsaso; Onaindia, Miren J; Apezetxea, Antonio; Gomez, Montserrat; Goyeneche, Muskilda; Fernandez, Magdalena; Vazquez, Begoña; Berroete, Miriam; Olarreaga, Itziar; Quintana, Jose M; Aguirre, Urko

    2017-01-01

    Abstract Background Outpatient Parenteral Antibiotic Therapy (OPAT) is a safe, effective and beneficial practice but studies report 10–20% of readmissions rate. The risk factors for readmissions in OPAT have been investigated, although there are no clinical tools that allow us to predict these situations. The main goal of this study is to develop and validate a predictive model for readmission in OPAT patients. Methods Prospective study was conducted during 1 year (10/2012–09/2013), 1488 patients with OPAT were recruited at 8 units of Hospital at Home in Spain. Potential risk factors related to patient demographics, lead-time factors, clinical and microbiologic features were collected. We developed the prediction model in a derivation sample and after that, we validated this model in the validation sample. Sensitivity, specificity and area under the curve were obtained and the calibration capacity of the models were evaluated using the Hosmer-Lemeshow test (H-L). Results The mean age of patients was 63 years (range 11–102), 58.74% men and most common diagnoses were urinary tract infections (23%). Our readmission rate during OPAT episode at home was 8.67% and the 30-days readmissions were 12.29%. The 72% of the readmissions during OPAT episode was related to the infectious pathology and 27.90% to the the patient’s comorbidity. The leading indicators for readmission were: gender, age, presence of caregivers, risk factor for infection, Charlsonand Barthel Index, microorganisme number, presence of multirresistent or micotic infection, venous access, antibiotic type and creatinine, proteine and leucocyte level at admissions. Finally, those factors included in the model were: antibiotic type (OR 3.93; IC 95% 1.90–8.11; P = 0.0002), presence of infection risk factor (OR 2.53; IC 95% 1.47–4.38; P = 0.001) and leucocytosis at admission (OR 2.21; IC 95% 1.32–3.71; P = 0.003). The AUC for the model was 0.72 (IC 95% 0.66–0.78) and the H-L value was 0

  13. Clinical profile of PiB-positive corticobasal syndrome.

    Directory of Open Access Journals (Sweden)

    James R Burrell

    Full Text Available BACKGROUND: Corticobasal syndrome (CBS is a multifaceted neurodegenerative disorder characterized by a combination of motor and cognitive deficits. Several different pathological entities, including Alzheimer's pathology, have been described in association with CBS. The present study aimed to establish clinical, neuropsychological, and neuroimaging features that could be useful in the distinction of CBS due to AD pathology from other CBS cases in life based on [(11C] Pittsburgh Compound B positron emission tomography (PiB-PET status. METHODS: Patients with CBS were prospectively recruited from a specialized cognitive disorders clinic. All patients underwent detailed clinical and neuropsychological assessment, with structural imaging using voxel-based analysis of magnetic resonance imaging. Alzheimer's pathology was detected using PiB-PET imaging, and PiB-positive and PiB-negative groups were compared. RESULTS: Fourteen CBS patients meeting defined criteria were included (7 male, 7 female; mean age 66.1+/-6.9 years; median symptom duration was 35.5+/-22.6 months and compared to 20 matched control subjects. Of the 14 patients, 4 were PiB-positive and 10 PiB-negative. There were no significant differences between PiB-positive and PiB-negative CBS patients in age, gender, education, symptom duration, or motor features. PiB-positive patients had greater visuospatial deficits, a higher rate of sentence repetition impairment, and more functional decline. Voxel-based morphometry analyses demonstrated extensive peri-insular and post-central atrophy in both groups, but PiB-positive patients had atrophy that extended to include the posterior part of the left superior temporal gyrus. CONCLUSIONS: Visuospatial function, aspects of language, and the pattern of cerebral atrophy may be useful in distinguishing patients with CBS due to underlying AD pathology.

  14. Demographic and clinical profiles in patients with acute urticaria.

    Science.gov (United States)

    Sánchez-Borges, M; Capriles-Hulett, A; Caballero-Fonseca, F

    2015-01-01

    Urticaria is a common cause for consultation in general and specialised medical practices. There is scarce information on the characteristics of patients suffering acute urticaria in Latin America. To investigate demographic and clinical features of patients with acute urticaria attending two allergy clinics in Caracas, Venezuela. A prospective study of all new patients who consulted during a three-year period because of acute urticaria. Information on age, gender, symptom duration, previous medical history, body distribution of wheals and angio-oedema, laboratory investigations, skin prick tests, and pharmacological treatment, was collected. Patients were classified according to their age as children/adolescents and adults. Two hundred and forty eight patients (177 adults and 71 children) were studied. Acute urticaria was more frequent in middle-aged atopic female patients. Lesions more often involved upper and lower limbs and head, and 31% of patients exhibited generalised urticaria. Laboratory investigations, performed only in selected cases, did not contribute to the final diagnosis. Most frequent subtypes of acute urticaria were spontaneous, dermographic, papular, and drug-induced urticaria. Most patients were treated with non-sedating antihistamines, with increased use of cetirizine and levocetirizine in children, while 5.6% of children and 20.3% of adults required the addition of short courses of systemic corticosteroids. Acute urticaria is a frequent cause of consultation for allergists, affecting more often middle-aged female atopic patients. The use of extensive complementary tests does not seem to be cost-effective for this clinical condition. Spontaneous, dermographic, papular and drug-induced urticaria are the most common subtypes. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  15. Clinical Profile and Visual Outcome of Ocular Bartonellosis in Malaysia

    Directory of Open Access Journals (Sweden)

    Chai Lee Tan

    2017-01-01

    Full Text Available Background. Ocular bartonellosis can present in various ways, with variable visual outcome. There is limited data on ocular bartonellosis in Malaysia. Objective. We aim to describe the clinical presentation and visual outcome of ocular bartonellosis in Malaysia. Materials and Methods. This was a retrospective review of patients treated for ocular bartonellosis in two ophthalmology centers in Malaysia between January 2013 and December 2015. The diagnosis was based on clinical features, supported by a positive Bartonella spp. serology. Results. Of the 19 patients in our series, females were predominant (63.2%. The mean age was 29.3 years. The majority (63.2% had unilateral involvement. Five patients (26.3% had a history of contact with cats. Neuroretinitis was the most common presentation (62.5%. Azithromycin was the antibiotic of choice (42.1%. Concurrent systemic corticosteroids were used in approximately 60% of cases. The presenting visual acuity was worse than 6/18 in approximately 60% of eyes; on final review, 76.9% of eyes had a visual acuity better than 6/18. Conclusion. Ocular bartonellosis tends to present with neuroretinitis. Azithromycin is a viable option for treatment. Systemic corticosteroids may be considered in those with poor visual acuity on presentation.

  16. Clinical and genetic profile of Indian children with primary hyperoxaluria

    Directory of Open Access Journals (Sweden)

    A Pinapala

    2017-01-01

    Full Text Available Primary hyperoxaluria (PH has heterogeneous renal manifestations in infants and children. This often leads to delay in diagnosis. In the past 3 years, genetic samples were sent for seven children with a clinical diagnosis of PH. Their medical records were reviewed for clinical presentation and outcomes. Of the seven children, three were males. The median age of presentation was 4.9 years with the youngest presenting at 3 months of age. Nephrolithiasis, the most common presentation was associated with renal dysfunction in two children. Two children with no significant history presented in end-stage renal disease (ESRD. The sibling of one of the children in ESRD, with a history of consanguinity in parents, was screened for asymptomatic nephrolithiasis. Bilateral multiple renal calculi were found in majority of children followed by echogenic kidneys on ultrasound examination. Genetic analysis suggested PH Type 1 in five children and type 2 in two children. The mutations detected in our cohort were different from the previously reported common mutations. There was no obvious genotype-phenotype correlation noticed. Three children in ESRD are on maintenance dialysis. Nephrolithiasis being a common presentation of PH needs prompt evaluation. Mutations are generally population specific, and whole gene sequence analysis is critical in diagnosis.

  17. Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers.

    Science.gov (United States)

    Jadhav, Manali; Nayak, Monalisha; Kumar, Swati; Venkatesh, Apoorva; Patel, Sandip K; Kumar, Vipin; Sharma, Sarthak; Samanta, Biaus; Deb, Satarupa; Karak, Avik; Verma, Sumit; Talukdar, Arunansu; Kochar, Sanjay K; Mansukhani, Preeti; Gandhi, Mayuri; Srivastava, Sanjeeva

    2017-11-01

    Dengue fever (DF) is a major global health burden with a pathophysiology that is still incompletely understood. Biomarkers that predict and explain susceptibility to DF and its progression to its more severe hemorrhagic form are much needed. DF is endemic in tropical and subtropical regions of the world, with a rapidly increasing incidence of disease severity. We conducted a clinical biomarker discovery study using both a case-control and longitudinal study design. Plasma proteome alterations in patients with DF (n = 12) and dengue hemorrhagic fever (DHF, n = 24) were analyzed in comparison to healthy controls (HCs, n = 16), using the isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics methodology (false discovery rate of 1%, ≥2 peptides). Several proteins such as the alpha-2 macroglobulin, angiotensinogen, apolipoprotein B-100, serotransferrin, and ceruloplasmin were upregulated (fold change >1.2) in all DHF cases, and downregulated in DF (fold change <0.83), compared with HCs. Plasma cytokine profiling (8 DF, 8 DHF, and 8 HC) on two consecutive time points, at day 0 (day of admission) and days 5-7, found significant elevation in IL-1RA, IL-7, TNF-α, MCP1-MCAF, and MIP-1β levels, but only in the DHF cases, which is the severe disease, and not in DF, compared with HCs (p < 0.05). These new observations on changes in the plasma proteome and cytokine profiles in patients with dengue infection identify several putative molecular leads for future biomarker development and precision medicine in relation to forecasting DF disease severity.

  18. Review article. Predicting disease onset in clinically healthy people

    Directory of Open Access Journals (Sweden)

    Zeliger . Harold I.

    2016-06-01

    Full Text Available Virtually all human disease is induced by oxidative stress. Oxidative stress, which is caused by toxic environmental exposure, the presence of disease, lifestyle choices, stress, chronic inflammation or combinations of these, is responsible for most disease. Oxidative stress from all sources is additive and it is the total oxidative stress from all sources that induces the onset of most disease. Oxidative stress leads to lipid peroxidation, which in turn produces Malondialdehyde. Serum malondialdehyde level is an additive parameter resulting from all sources of oxidative stress and, therefore, is a reliable indicator of total oxidative stress which can be used to predict the onset of disease in clinically asymptomatic individuals and to suggest the need for treatment that can prevent much human disease.

  19. Graphics and statistics for cardiology: clinical prediction rules.

    Science.gov (United States)

    Woodward, Mark; Tunstall-Pedoe, Hugh; Peters, Sanne Ae

    2017-04-01

    Graphs and tables are indispensable aids to quantitative research. When developing a clinical prediction rule that is based on a cardiovascular risk score, there are many visual displays that can assist in developing the underlying statistical model, testing the assumptions made in this model, evaluating and presenting the resultant score. All too often, researchers in this field follow formulaic recipes without exploring the issues of model selection and data presentation in a meaningful and thoughtful way. Some ideas on how to use visual displays to make wise decisions and present results that will both inform and attract the reader are given. Ideas are developed, and results tested, using subsets of the data that were used to develop the ASSIGN cardiovascular risk score, as used in Scotland. 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/.

  20. Are dangerous offenders different from other offenders? A clinical profile.

    Science.gov (United States)

    Langevin, Ron; Curnoe, Suzanne

    2014-07-01

    The Canadian dangerous offender (DO) statute requires the assistance of psychiatrists and psychologists in evaluating offenders' potential danger and risk of future offenses, without substantive supporting empirical clinical research on the topic. The present study compared 62 men facing Canadian DO applications to 2,414 non-DO sexual and violent offenders (ACs) and 62 non-DO offenders matched on offense type (MCs). DOs differed significantly from ACs on 30 of 45 variables and from MCs only on 6. More DOs than MCs had an extensive criminal history, were psychopaths, and had more school truancy. Compared with ACs, DOs had less education and more school adjustment problems, more disturbed childhoods, and more often were diagnosed with sadism, psychopathy, and substance abuse problems. Total sexual and violent offense convictions provided the best but weak distinction of DOs from ACs. The "three strikes" law is noted and early intervention in DOs' criminal careers is discussed. © The Author(s) 2013.

  1. Childhood Acute Bacterial Meningitis: Clinical Spectrum, Bacteriological Profile and Outcome.

    Science.gov (United States)

    Bari, Attia; Zeeshan, Fatima; Zafar, Aiza; Ejaz, Hassan; Iftikhar, Aisha; Rathore, Ahsan Waheed

    2016-10-01

    To determine the disease pattern, etiological agents and outcome of childhood acute bacterial meningitis. Adescriptive study. Department of Paediatric Medicine, The Children's Hospital, Lahore, from January to December 2012. Atotal of 199 children between the ages of 1 month and 5 years, admitted with the diagnosis of meningitis on the basis of clinical findings and positive cerebrospinal fluid (CSF), were included. In all patients, complete blood count (CBC), CSF culture sensitivity, and blood culture sensitivity were performed. Data was analysed using SPSS version 20. Out of 199 children, 127 (63.8%) were males with M:F ratio of 1.7:1. Mean age was 11.33 ±12 months. Maximum numbers of children were bacterial meningitis mostly affected children under the age of 1 year. CSF culture revealed both Grampositive and Gram-negative bacteria. The most common pathogen in children who died was streptococcus pneumoniae.

  2. Prediction profiles for nutritional supplement use among young German elite athletes.

    Science.gov (United States)

    Dietz, Pavel; Ulrich, Rolf; Niess, Andreas; Best, Raymond; Simon, Perikles; Striegel, Heiko

    2014-12-01

    Nutritional supplements (NS) are defined as concentrated sources of nutrients and other substances that have a nutritional or physiological effect and that are used in high frequency among athletes. The study aimed to create a prediction profile for young elite athletes to identify those athletes who have a higher relative risk for using NS. The second objective was to examine the hypothesis that the consumption of NS paves a gateway for the use of illicit drugs and doping substances. A self-designed anonymous paper-and-pencil questionnaire was used to examine the prevalence of NS consumption, doping, and illicit drug use in elite athletes with a mean age of 17 years (SD = 4 years). Logistic regression analysis was employed to assess whether NS consumption can be predicted by independent variables (e.g., biographical data, training characteristics, drug consumption behavior) to create the prediction profile for NS use. 55% and 5% of the athletes (n = 536) responded positively to having used NS and illicit drugs, respectively. Nutritional supplement consumption was positively correlated with age (OR: 1.92; CI: 1.21 to 3.05), the desire to enhance performance to become an Olympic or World Champion (OR: 3.72; CI: 2.33 to 6.01), and being educated about NS (OR: 2.76; CI: 1.73 to 4.45). It was negatively correlated with training frequency (OR: 0.55; CI: 0.35 to 0.86) and the use of nicotine (OR: 0.29; CI: 0.1 to 0.74) but did not correlate with illicit drug use and alcohol consumption. The present results show that NS are used on a large scale in elite sports. The prediction profile presented in this article may help to identify those athletes who have a high risk for using NS to plan potential education and prevention models more individually.

  3. Nonalcoholic fatty liver disease in Brazil. Clinical and histological profile.

    Science.gov (United States)

    Cotrim, Helma P; Parise, Edison R; Oliveira, Claudia P M S; Leite, Natalhie; Martinelli, Ana; Galizzi, João; Silva, Rita de Cássia; Mattos, Angelo; Pereira, Leila; Amorim, Waldir; Ivantes, Claúdia; Souza, Francisco; Costa, Marcelo; Maia, Lizomar; Pessoa, Mário; Oliveira, Frederico

    2011-01-01

    The epidemiology and clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in South America are not well known. Brazil is a largest country in this part of the world and the present study aimed to contribute with this information. This descriptive study included patients from medical centers around Brazil, who had diagnosis of NAFLD. They were selected from chart review and also prospectively in Hepatology out-clinics. Patients with history of alcohol intake and others liver diseases were excluded. Histological diagnosis included: steatosis or steatohepatitis (steatosis, ballooning of hepatocytes or fibrosis). The criteria to perform a liver biopsy was ALT or AST > 1.5 x normal levels. A total of 1280 patients from 16 Brazilian centers and all five regions were included. The mean age was 49.68 ± 13.59 years; 53.3% were males and 85% were asymptomatic. Hyperlipidemia was observed in 66.8% cases, obesity in 44.7%, overweight in 44.4%, diabetes in 22.7%, and toxins exposure in 10%. Metabolic syndrome was observed in 41.3% cases. Elevated levels of ALT, AST and GGT were observed in 55.8%, 42.2% and 63.1% cases, respectively. Liver biopsy performed in 437 cases showed: isolate steatosis in 42% cases, steatohepatitis in 58% and 27% of them also presented fibrosis. Cirrhosis was observed in 15.4% and hepatocellular carcinoma in 0.7%. NAFLD in Brazil is more frequent in asymptomatic males; steatohepatitis with fibrosis and cirrhosis were a significant diagnosis. The genetic predisposition and lifestyle should be influenced in the spectrum; however these findings deserve a future investigation.

  4. Clinical Profile of Hypertensive Emergencies in an Intensive Care Unit.

    Science.gov (United States)

    Dhadke, Shubhangi V; Dhadke, Vithal N; Batra, Dhruv S

    2017-05-01

    To study the prevalence of hypertensive emergencies in an ICU set up and to study the clinical presentation of hypertensive emergencies related to cardiovascular, neurological and renovascular system. Type of Study: Cross-sectional, descriptive study. Two years from 1st December 2011 till 30th November 2013. 50 patients of hypertensive emergencies admitted to the intensive care unit of Dr. V.M. Govt. Medical College, Solapur were studied. Inclusion criteria All patients above 18 years of age. Systolic blood pressure > 180 mmHg Diastolic blood pressure > 120 mm Hg Exclusion criteria Pregnancy Patients with diabetes mellitus We classified as hypertensive emergencies all cases in which the increase in blood pressure was associated with one or more of the following types of acute or ongoing end-organ damage: hypertensive encephalopathy; stroke (cerebral infarction or intracerebral or subarachnoid hemorrhage, transient ischemic attack); acute pulmonary edema, left ventricular failure; acute myocardial infarction or unstable angina, progressive renal insufficiency features suggestive of retinopathy. All these conditions were diagnosed clinically or by approprriate diagnostic tests. most common presenting complaint in patients was breathlessness seen in 17 patients (34%), followed by neurological deficit in 14 patients (28%). Thirteen patients (26%) had complaints of headache, whereas 12 (24%) patients complained of chest pain on admission. Other symptoms included vomiting, giddiness, psychomotor agitation, and decreased urine output. Out of a total of 4076 admissions during the study period in the intensive care unit we had 50 cases of hypertensive emergencies with prevalence of 1.22% in our intensive care unit. Most common organ involvement was the retina followed by cardiovascular system, renal and then the central nervous system.

  5. Associations of Streptococcus suis serotype 2 ribotype profiles with clinical disease and antimicrobial resistance

    DEFF Research Database (Denmark)

    Rasmussen, S. R.; Aarestrup, Frank Møller; Jensen, N. E.

    1999-01-01

    A total of 122 Streptococcus suis serotype 2 strains were characterized thoroughly by comparing clinical and pathological observations, ribotype profiles, and antimicrobial resistance. Twenty-one different ribotype profiles were found and compared by cluster analysis, resulting in the identificat......A total of 122 Streptococcus suis serotype 2 strains were characterized thoroughly by comparing clinical and pathological observations, ribotype profiles, and antimicrobial resistance. Twenty-one different ribotype profiles were found and compared by cluster analysis, resulting...... ribotypes were almost exclusively isolated from pigs with meningitis, while strains of the other dominant ribotype were never associated with meningitis. This second ribotype was isolated only from pigs with pneumonia, endocarditis, pericarditis, or septicemia. Cluster analysis revealed that strains...... of resistance to antibiotics because strains isolated from pigs with meningitis were resistant to sulfamethazoxazole and strains isolated from pigs with pneumonia, endocarditis, pericarditis, or septicemia were resist-ant to tetracycline....

  6. Automatic prediction of coronary artery disease from clinical narratives.

    Science.gov (United States)

    Buchan, Kevin; Filannino, Michele; Uzuner, Özlem

    2017-08-01

    Coronary Artery Disease (CAD) is not only the most common form of heart disease, but also the leading cause of death in both men and women (Coronary Artery Disease: MedlinePlus, 2015). We present a system that is able to automatically predict whether patients develop coronary artery disease based on their narrative medical histories, i.e., clinical free text. Although the free text in medical records has been used in several studies for identifying risk factors of coronary artery disease, to the best of our knowledge our work marks the first attempt at automatically predicting development of CAD. We tackle this task on a small corpus of diabetic patients. The size of this corpus makes it important to limit the number of features in order to avoid overfitting. We propose an ontology-guided approach to feature extraction, and compare it with two classic feature selection techniques. Our system achieves state-of-the-art performance of 77.4% F1 score. Copyright © 2017. Published by Elsevier Inc.

  7. A new metric of inclusive fitness predicts the human mortality profile.

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    Saul J Newman

    Full Text Available Biological species have evolved characteristic patterns of age-specific mortality across their life spans. If these mortality profiles are shaped by natural selection they should reflect underlying variation in the fitness effect of mortality with age. Direct fitness models, however, do not accurately predict the mortality profiles of many species. For several species, including humans, mortality rates vary considerably before and after reproductive ages, during life-stages when no variation in direct fitness is possible. Variation in mortality rates at these ages may reflect indirect effects of natural selection acting through kin. To test this possibility we developed a new two-variable measure of inclusive fitness, which we term the extended genomic output or EGO. Using EGO, we estimate the inclusive fitness effect of mortality at different ages in a small hunter-gatherer population with a typical human mortality profile. EGO in this population predicts 90% of the variation in age-specific mortality. This result represents the first empirical measurement of inclusive fitness of a trait in any species. It shows that the pattern of human survival can largely be explained by variation in the inclusive fitness cost of mortality at different ages. More generally, our approach can be used to estimate the inclusive fitness of any trait or genotype from population data on birth dates and relatedness.

  8. Profile control simulations and experiments on TCV: a controller test environment and results using a model-based predictive controller

    Science.gov (United States)

    Maljaars, E.; Felici, F.; Blanken, T. C.; Galperti, C.; Sauter, O.; de Baar, M. R.; Carpanese, F.; Goodman, T. P.; Kim, D.; Kim, S. H.; Kong, M.; Mavkov, B.; Merle, A.; Moret, J. M.; Nouailletas, R.; Scheffer, M.; Teplukhina, A. A.; Vu, N. M. T.; The EUROfusion MST1-team; The TCV-team

    2017-12-01

    The successful performance of a model predictive profile controller is demonstrated in simulations and experiments on the TCV tokamak, employing a profile controller test environment. Stable high-performance tokamak operation in hybrid and advanced plasma scenarios requires control over the safety factor profile (q-profile) and kinetic plasma parameters such as the plasma beta. This demands to establish reliable profile control routines in presently operational tokamaks. We present a model predictive profile controller that controls the q-profile and plasma beta using power requests to two clusters of gyrotrons and the plasma current request. The performance of the controller is analyzed in both simulation and TCV L-mode discharges where successful tracking of the estimated inverse q-profile as well as plasma beta is demonstrated under uncertain plasma conditions and the presence of disturbances. The controller exploits the knowledge of the time-varying actuator limits in the actuator input calculation itself such that fast transitions between targets are achieved without overshoot. A software environment is employed to prepare and test this and three other profile controllers in parallel in simulations and experiments on TCV. This set of tools includes the rapid plasma transport simulator RAPTOR and various algorithms to reconstruct the plasma equilibrium and plasma profiles by merging the available measurements with model-based predictions. In this work the estimated q-profile is merely based on RAPTOR model predictions due to the absence of internal current density measurements in TCV. These results encourage to further exploit model predictive profile control in experiments on TCV and other (future) tokamaks.

  9. Clinical prediction rule for differentiating tuberculous from viral meningitis.

    Science.gov (United States)

    Hristea, A; Olaru, I D; Baicus, C; Moroti, R; Arama, V; Ion, M

    2012-06-01

    The Professor Dr Matei Bals National Institute of Infectious Diseases, Bucharest, Romania. To create a prediction rule to enable clinicians to differentiate patients with tuberculous meningitis (TBM) from those with viral meningitis. We retrospectively analysed patients admitted to a tertiary care facility between 2001 and 2011 with viral meningitis and TBM. Patients were defined as having TBM according to a recently published consensus definition, and as viral meningitis if a viral aetiology was confirmed, or after ruling out bacterial, fungal and non-infectious causes of meningitis. We identified 433 patients with viral meningitis and 101 TBM patients and compared their clinical and laboratory features. Multivariable analysis showed a statistically significant association between TBM and the following variables: duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures, mild focal signs, multiple cranial nerve palsies, dense hemiplegia or paraparesis), cerebrospinal fluid/blood glucose ratio 100 mg/dl. We propose a diagnostic score based on the coefficients derived from the logistic regression model with a sensitivity and specificity for TBM of respectively 92% and 94%. Our study suggests that easily available clinical and laboratory data are very useful for differentiating TBM from other causes of meningitis.

  10. Improving Clinical Prediction of Bipolar Spectrum Disorders in Youth

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    Thomas W. Frazier

    2014-03-01

    Full Text Available This report evaluates whether classification tree algorithms (CTA may improve the identification of individuals at risk for bipolar spectrum disorders (BPSD. Analyses used the Longitudinal Assessment of Manic Symptoms (LAMS cohort (629 youth, 148 with BPSD and 481 without BPSD. Parent ratings of mania symptoms, stressful life events, parenting stress, and parental history of mania were included as risk factors. Comparable overall accuracy was observed for CTA (75.4% relative to logistic regression (77.6%. However, CTA showed increased sensitivity (0.28 vs. 0.18 at the expense of slightly decreased specificity and positive predictive power. The advantage of CTA algorithms for clinical decision making is demonstrated by the combinations of predictors most useful for altering the probability of BPSD. The 24% sample probability of BPSD was substantially decreased in youth with low screening and baseline parent ratings of mania, negative parental history of mania, and low levels of stressful life events (2%. High screening plus high baseline parent-rated mania nearly doubled the BPSD probability (46%. Future work will benefit from examining additional, powerful predictors, such as alternative data sources (e.g., clinician ratings, neurocognitive test data; these may increase the clinical utility of CTA models further.

  11. Clinical predictive factors of sildenafil response: a penile hemodynamic study.

    Science.gov (United States)

    Elhanbly, S M; Elkholy, A A-M; Alghobary, M; Abou Al-Ghar, M

    2015-03-01

    Phosphodiestrase-5 inhibitors are an important line of treatment for erectile dysfunction (ED). To detect the clinical and hemodynamic predictors of sildenafil response, we conducted this study on 124 Egyptian men with ED. All patients were evaluated by thorough history and clinical assessment with measurement of the abridged international index of erectile function-5 (IIEF-5) score. All patients were then subjected to intracavernosal injection (ICI) of trimix and pharmaco-penile duplex ultrasonography (PPDU). Patients were then classified into sildenafil responders and non-responders after six consecutive doses of 100 mg sildenafil. On doing the binary logistic stepwise regression analysis, only ED duration, IIEF-5 score, and response to ICI were the significant independent predictors of sildenafil response. These three parameters together correctly predicted the sildenafil response by 81.5% (p value <0.001). With the receiver operator characteristic curve analysis, the cut-off value of ED duration was 2.5 years and it was 14 for the IIEF-5 score. These findings indicate that ED duration, the IIEF-5 score and response to ICI are more significant predictors of sildenafil response than the more expensive and time-consuming PPDU testing. © 2015 American Society of Andrology and European Academy of Andrology.

  12. Cri-Du-Chat Syndrome: Clinical Profile and Chromosomal Microarray Analysis in Six Patients.

    Science.gov (United States)

    Espirito Santo, Layla Damasceno; Moreira, Lília Maria Azevedo; Riegel, Mariluce

    2016-01-01

    Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. The disease severity, levels of intellectual and developmental delay, and patient prognosis have been related to the size and position of the deletion. Aiming to establish genotype-phenotype correlations, we applied array-CGH to evaluate six patients carrying cytogenetically detected deletions of the short arm of chromosome 5 who were followed at a genetics community service. The patients' cytogenetic and clinical profiles were reevaluated. A database review was performed to predict additional genes and regulatory elements responsible for the characteristic phenotypic and behavioral traits of this disorder. Array-CGH analysis allowed for delineation of the terminal deletions, which ranged in size from approximately 11.2 Mb to 28.6 Mb, with breakpoints from 5p15.2 to 5p13. An additional dup(8)(p23) (3.5 Mb), considered to be a benign copy number variation, was also observed in one patient. The correlation coefficient value (ρ = 0.13) calculated indicated the presence of a weak relationship between developmental delay and deletion size. Genetic background, family history, epigenetic factors, quantitative trait locus polymorphisms, and environmental factors may also affect patient phenotype and must be taken into account in genotype-phenotype correlations.

  13. Cri-Du-Chat Syndrome: Clinical Profile and Chromosomal Microarray Analysis in Six Patients

    Directory of Open Access Journals (Sweden)

    Layla Damasceno Espirito Santo

    2016-01-01

    Full Text Available Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. The disease severity, levels of intellectual and developmental delay, and patient prognosis have been related to the size and position of the deletion. Aiming to establish genotype-phenotype correlations, we applied array-CGH to evaluate six patients carrying cytogenetically detected deletions of the short arm of chromosome 5 who were followed at a genetics community service. The patients’ cytogenetic and clinical profiles were reevaluated. A database review was performed to predict additional genes and regulatory elements responsible for the characteristic phenotypic and behavioral traits of this disorder. Array-CGH analysis allowed for delineation of the terminal deletions, which ranged in size from approximately 11.2 Mb to 28.6 Mb, with breakpoints from 5p15.2 to 5p13. An additional dup(8(p23 (3.5 Mb, considered to be a benign copy number variation, was also observed in one patient. The correlation coefficient value (ρ=0.13 calculated indicated the presence of a weak relationship between developmental delay and deletion size. Genetic background, family history, epigenetic factors, quantitative trait locus polymorphisms, and environmental factors may also affect patient phenotype and must be taken into account in genotype-phenotype correlations.

  14. Tubercular meningitis in children: Clinical, pathological, and radiological profile and factors associated with mortality

    Directory of Open Access Journals (Sweden)

    Anil V Israni

    2016-01-01

    Full Text Available Context: Childhood tuberculosis is a major public health problem in developing countries with tubercular meningitis being a serious complication with high mortality and morbidity. Aim: To study the clinicopathological as well as radiological profile of childhood tuberculous meningitis (TBM cases. Settings and Design: Prospective, observational study including children <14 years of age with TBM admitted in a tertiary care hospital from Western India. Subjects and Methods: TBM was diagnosed based on predefined criteria. Glassgow coma scale (GCS and intracranial pressure (ICP was recorded. Staging was done as per British Medical Council Staging System. Mantoux test, chest X-ray, cerebrospinal fluid (CSF examination, neuroimaging, and other investigations were done to confirm TB. Statistical Analysis Used: STATA software (version 9.0 was used for data analysis. Various risk factors were determined using Chi-square tests, and a P< 0.05 was considered significant. Results: Forty-seven children were included, of which 11 (24.3% died. Fever was the most common presenting symptom, and meningismus was the most common sign. Twenty-nine (62% children presented with Stage III disease. Stage III disease, low GCS, and raised ICP were predictors of mortality. Findings on neuroimaging or CSF examination did not predict mortality. Conclusions: Childhood TBM presents with nonspecific clinical features. Stage III disease, low GCS, lack of Bacillus Calmette–Gu͹rin vaccination at birth and raised ICP seem to the most important adverse prognostic factors.

  15. Model Predictive Control with Integral Action for Current Density Profile Tracking in NSTX-U

    Science.gov (United States)

    Ilhan, Z. O.; Wehner, W. P.; Schuster, E.; Boyer, M. D.

    2016-10-01

    Active control of the toroidal current density profile may play a critical role in non-inductively sustained long-pulse, high-beta scenarios in a spherical torus (ST) configuration, which is among the missions of the NSTX-U facility. In this work, a previously developed physics-based control-oriented model is embedded in a feedback control scheme based on a model predictive control (MPC) strategy to track a desired current density profile evolution specified indirectly by a desired rotational transform profile. An integrator is embedded into the standard MPC formulation to reject various modeling uncertainties and external disturbances. Neutral beam powers, electron density, and total plasma current are used as actuators. The proposed MPC strategy incorporates various state and actuator constraints directly into the control design process by solving a constrained optimization problem in real-time to determine the optimal actuator requests. The effectiveness of the proposed controller in regulating the current density profile in NSTX-U is demonstrated in closed-loop nonlinear simulations. Supported by the US DOE under DE-AC02-09CH11466.

  16. ProFile Vortex and Vortex Blue Nickel-Titanium Rotary Instruments after Clinical Use.

    Science.gov (United States)

    Shen, Ya; Zhou, Huimin; Coil, Jeffrey M; Aljazaeri, Bassim; Buttar, Rene; Wang, Zhejun; Zheng, Yu-feng; Haapasalo, Markus

    2015-06-01

    The aim of this study was to analyze the incidence and mode of ProFile Vortex and Vortex Blue instrument defects after clinical use in a graduate endodontic program and to examine the impact of clinical use on the instruments' metallurgical properties. A total of 330 ProFile Vortex and 1136 Vortex Blue instruments from the graduate program were collected after each had been used in 3 teeth. The incidence and type of instrument defects were analyzed. The lateral surfaces and fracture surfaces of the fractured files were examined by using scanning electron microscopy. Unused and used instruments were examined by full and partial differential scanning calorimetry. No fractures were observed in the 330 ProFile Vortex instruments, whereas 20 (6.1%) revealed bent or blunt defects. Only 2 of the 1136 Vortex Blue files fractured during clinical use. The cause of fracture was shear stress. The fractures occurred at the tip end of the spirals. Only 1.8% (21 of 1136) of the Vortex Blue files had blunt tips. Austenite-finish temperatures were very similar for unused and used ProFile Vortex files and were all greater than 50°C. The austenite-finish temperatures of used and unused Vortex Blue files (38.5°C) were lower than those in ProFile Vortex instruments (P Vortex Blue files had an obvious 2-stage transformation, martensite-to-R phase and R-to-austenite phase. The trends of differential scanning calorimetry plots of unused Vortex Blue instruments and clinically used instruments were very similar. The risk of ProFile Vortex and Vortex Blue instrument fracture is very low when instruments are discarded after clinical use in the graduate endodontic program. The Vortex Blue files have metallurgical behavior different from ProFile Vortex instruments. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  17. Profile of special needs patients at a pediatric dentistry clinic

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    Sílvio Augusto Fernandes de Menezes

    2011-06-01

    Full Text Available Objective: To assess the characteristics of special needs patients assisted at the Clinic of Pediatric Dentistry, Faculty of Dentistry, Federal University of Pará. Methods: A descriptive observational study conducted from March 2007 to December 2009, assessing 137 records of which were extracted the following data: gender, age, origin, current and past medical history, type of special needs and major oral diseases. We applied descriptive statistics, one-dimensional frequency table and prepared graphs of the results. Results: We found 77 (56.2% male patients, with mean age of 8.1 years; 118 (86.2% living in the state capital of Para, 21 (15.3% with respiratory problems, 37 (27.3% with some allergy to medicationsand 54 (39.4% making use of controlled drugs. Regarding the type of special need, we observed that 29 (28.3% had neurologic and psychomotor delay and the primary oral disease found was dental caries, affecting 84 (61.3% subjects. Conclusion: The assessedprofile of patients with special needs is characterized by patients residing in the state capital of Para, with predominance of male children, with neurologic and psychomotor delay, witha mean age of 8.1 years, presenting mainly caries.

  18. Data Resource Profile: Clinical Practice Research Datalink (CPRD)

    Science.gov (United States)

    Herrett, Emily; Gallagher, Arlene M; Bhaskaran, Krishnan; Forbes, Harriet; Mathur, Rohini; van Staa, Tjeerd; Smeeth, Liam

    2015-01-01

    The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research. PMID:26050254

  19. Comparing Clinical Profiles in Alzheimer's Disease and Parkinson's Disease Dementia

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    Martin R. Farlow

    2013-09-01

    Full Text Available Background: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD and Parkinson's disease dementia (PDD may improve the interpretation of drug effects and the design of future studies. Methods: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD. Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog, Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL scale, 10-item Neuropsychiatric Inventory (NPI-10 and the ADCS-Clinical Global Impression of Change (CGIC was compared [standardized difference (Cohen's d, similar if Results: Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47 and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58 were higher in AD; PDD patients were more impaired in the language (0.23 and praxis (0.34 domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14 and improvement on the NPI-10 (0.11 compared with patients with PDD. Conclusion: Differing patterns of impairment occur in AD and PDD.

  20. INDUSTRIAL OCULAR TRAUMA- A CLINICAL AND EPIDEMIOLOGICAL PROFILE

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    Sahiba Bedi

    2017-05-01

    Full Text Available BACKGROUND Incidence of ocular injuries is on the rise and is the commonest cause of unilateral blindness. Some individuals are at increased risk of eye injury as a result of their occupation. MATERIALS AND METHODS Data was obtained from case files of the patients in the retrospective group. In the prospective group, a complete ophthalmological examination including fundus was done for each patient. A final visual outcome was recorded at the end of 3 months post trauma based on visual acuity. Settings and Design- This was a 1 year retrospective and 1 year prospective study done in the Department of Ophthalmology, CMC, Ludhiana. Statistical Analysis- The clinical data collected was analysed for frequencies and proportions. RESULTS The industries where ocular trauma was found to be highest were the metal industries (61.7% followed by automobile industries (19.1%. Textile and woollen industry accounted for 5.8% cases. Metal objects caused injury in 81.7% of the cases. CONCLUSION Injuries occurring in industries are severe and males in age group of 21-30 years are most vulnerable. In view of costly medical care required and loss of productivity, preventive measures must be taken to avoid such injuries.

  1. Familial epilepsy in Algeria: Clinical features and inheritance profiles.

    Science.gov (United States)

    Chentouf, Amina; Dahdouh, Aïcha; Guipponi, Michel; Oubaiche, Mohand Laïd; Chaouch, Malika; Hamamy, Hanan; Antonarakis, Stylianos E

    2015-09-01

    To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  2. A CLINICAL AND HISTOPATHOLOGICAL PROFILE OF PATIENTS WITH CUTANEOUS TUBERCULOSIS

    Science.gov (United States)

    Puri, Neerja

    2011-01-01

    Extrapulmonary tuberculosis constitutes about 10% of all cases of tuberculosis, and cutaneous tuberculosis makes up only a small proportion of these cases. Despite prevention programs, tuberculosis is still progressing endemically in developing countries. Commonest clinical variant of cutaneous tuberculosis in our study was lupus vulgaris seen in 55% patients followed by scrufuloderma seen in 25% patients followed by orificial tuberculosis, tuberculosis verrucosa cutis, papulonecrotic tuberculid, and erythema induratum seen in 5% each. The commonest site of involvement was limbs seen in 50% patients followed by neck seen in 25% patients, face in 15%, and trunk in 10% patients. Maximum percentage of patients (55%) had duration of cutaneous tuberculosis between 6–12 months followed by 35% between 13–24 months, 5% had duration of cutaneous tuberculosis less than 6 months, and the rest 5% had duration more than 24 months. The commonest histopathological feature in our study was tuberculoid granuloma with epitheloid cell and Langhans giant cells seen in 70% patients, hyperkeratosis was seen in 15% patients and AFB bacilli were seen in 5% patients. PMID:22121276

  3. A clinical and histopathological profile of patients with cutaneous tuberculosis

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    Neerja Puri

    2011-01-01

    Full Text Available Extrapulmonary tuberculosis constitutes about 10% of all cases of tuberculosis, and cutaneous tuberculosis makes up only a small proportion of these cases. Despite prevention programs, tuberculosis is still progressing endemically in developing countries. Commonest clinical variant of cutaneous tuberculosis in our study was lupus vulgaris seen in 55% patients followed by scrufuloderma seen in 25% patients followed by orificial tuberculosis, tuberculosis verrucosa cutis, papulonecrotic tuberculid, and erythema induratum seen in 5% each. The commonest site of involvement was limbs seen in 50% patients followed by neck seen in 25% patients, face in 15%, and trunk in 10% patients. Maximum percentage of patients (55% had duration of cutaneous tuberculosis between 6-12 months followed by 35% between 13-24 months, 5% had duration of cutaneous tuberculosis less than 6 months, and the rest 5% had duration more than 24 months. The commonest histopathological feature in our study was tuberculoid granuloma with epitheloid cell and Langhans giant cells seen in 70% patients, hyperkeratosis was seen in 15% patients and AFB bacilli were seen in 5% patients.

  4. Clinical Prediction Rules for Physical Therapy Interventions: A Systematic Review

    Science.gov (United States)

    Beneciuk, Jason M; Bishop, Mark D; George, Steven Z

    2009-01-01

    Background and Purpose: Clinical prediction rules (CPRs) involving physical therapy interventions have been published recently. The quality of the studies used to develop the CPRs was not previously considered, a fact that has potential implications for clinical applications and future research. The purpose of this systematic review was to determine the quality of published CPRs developed for physical therapy interventions. Methods: Relevant databases were searched up to June 2008. Studies were included in this review if the explicit purpose was to develop a CPR for conditions commonly treated by physical therapists. Validated CPRs were excluded from this review. Study quality was independently determined by 3 reviewers using standard 18-item criteria for assessing the methodological quality of prognostic studies. Percentage of agreement was calculated for each criterion, and the intraclass correlation coefficient (ICC) was determined for overall quality scores. Results: Ten studies met the inclusion criteria and were included in this review. Percentage of agreement for individual criteria ranged from 90% to 100%, and the ICC for the overall quality score was .73 (95% confidence interval=.27–.92). Criteria commonly not met were adequate description of inclusion or exclusion criteria, inclusion of an inception cohort, adequate follow-up, masked assessments, sufficient sample sizes, and assessments of potential psychosocial factors. Quality scores for individual studies ranged from 48.2% to 74.0%. Discussion and Conclusion: Validation studies are rarely reported in the literature; therefore, CPRs derived from high-quality studies may have the best potential for use in clinical settings. Investigators planning future studies of physical therapy CPRs should consider including inception cohorts, using longer follow-up times, performing masked assessments, recruiting larger sample sizes, and incorporating psychological and psychosocial assessments. PMID:19095806

  5. [Clinical profile and 90-day mortality in centenarian patients attended in emergency departments].

    Science.gov (United States)

    Martín-Sánchez, Francisco Javier; Fernández-Alonso, Cesáreo; Hormigo, Ana Isabel; Jiménez-Díaz, Gregorio; Roiz, Honan; Bermejo-Boixareu, Cristina; Rodríguez-Salazar, Jaime; Fernández Pérez, Cristina; Gil-Gregorio, Pedro

    2016-01-01

    To determine the clinical profile and to develop a model to predict 90-day mortality in centenarian patients attended in emergency departments (ED). This was an observational, retrospective, multicentre cohort study including patients >99years attended in 5 ED in the Community of Madrid from January to December 2012. Demographic variables were recorded, as well as, comorbidities, cognitive, functional, social basal status, geriatric syndromes, acute episode, and hospital and social resources use, and 90-day mortality. The study included 209patients aged 101years (SD 1.7) of whom 161 (77.0%) were female. Sixty four (32.5%) had severe comorbidity (Charlson index≥3), 101 (49.8%) on multiple medication, 100 (52.6%) had cognitive impairment, 82 (42.3%) had severe functional dependence, 85 (40.7%) were institutionalised, and 190 (94.5%) had a geriatric syndrome. Dyspnoea (26.8%), followed by falls (12.4%) were the most common causes of attendance. One hundred and eighteen (56.5%) were admitted, and 58 out of 174 (33.3%) died in the first 90days. The model to predict 90-day overall mortality included male sex (OR 2.42 95% CI=0.97-6.04; P=.059), emergency care in the previous 3months (OR 4.08 95% CI=1.26-13.16; P=.019) and the hospitalization by index event (OR 8.63 95% CI=3.25-22.9; P<.001) and this model had an area under ROC curve of 0.776 (95% CI=0.70-0.85; P<.001). Centenarian patients attended in ED had a significant frailty and one in three cases died in the first 90days after being attended, and this was associated with male sex, emergency care in the previous 3months, and hospitalisation. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.

    Science.gov (United States)

    Brandl, Miriam B; Pasquier, Eddy; Li, Fuhai; Beck, Dominik; Zhang, Sufang; Zhao, Hong; Kavallaris, Maria; Wong, Stephen T C

    2014-12-01

    An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Metformin associated lactic acidosis (MALA): clinical profiling and management.

    Science.gov (United States)

    Moioli, Alessandra; Maresca, Barbara; Manzione, Andrea; Napoletano, Antonello Maria; Coclite, Daniela; Pirozzi, Nicola; Punzo, Giorgio; Menè, Paolo

    2016-12-01

    Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60 % of them with GFR between 30 and 60 ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62 %) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92 mmol/l vs 5.7 mmol/l, p = 0.03). The overall death rate has been 31 %, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p > 0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.

  8. Development of fuzzy logic system to predict the SAW weldment shape profiles

    Science.gov (United States)

    Narang, H. K.; Mahapatra, M. M.; Jha, P. K.; Biswas, P.

    2012-09-01

    A fuzzy model was presented to predict the weldment shape profile of submerged arc welds (SAW) including the shape of heat affected zone (HAZ). The SAW bead-on-plates were welded by following a full factorial design matrix. The design matrix consisted of three levels of input welding process parameters. The welds were cross-sectioned and etched, and the zones were measured. A mapping technique was used to measure the various segments of the weld zones. These mapped zones were used to build a fuzzy logic model. The membership functions of the fuzzy model were chosen for the accurate prediction of the weld zone. The fuzzy model was further tested for a set of test case data. The weld zone predicted by the fuzzy logic model was compared with the experimentally obtained shape profiles and close agreement between the two was noted. The mapping technique developed for the weld zones and the fuzzy logic model can be used for on-line control of the SAW process. From the SAW fuzzy logic model an estimation of the fusion and HAZ can also be developed.

  9. Protein profiling reveals consequences of lifestyle choices on predicted biological aging.

    Science.gov (United States)

    Enroth, Stefan; Enroth, Sofia Bosdotter; Johansson, Åsa; Gyllensten, Ulf

    2015-12-01

    Ageing is linked to a number of changes in how the body and its organs function. On a molecular level, ageing is associated with a reduction of telomere length, changes in metabolic and gene-transcription profiles and an altered DNA-methylation pattern. Lifestyle factors such as smoking or stress can impact some of these molecular processes and thereby affect the ageing of an individual. Here we demonstrate by analysis of 77 plasma proteins in 976 individuals, that the abundance of circulating proteins accurately predicts chronological age, as well as anthropometrical measurements such as weight, height and hip circumference. The plasma protein profile can also be used to identify lifestyle factors that accelerate and decelerate ageing. We found smoking, high BMI and consumption of sugar-sweetened beverages to increase the predicted chronological age by 2-6 years, while consumption of fatty fish, drinking moderate amounts of coffee and exercising reduced the predicted age by approximately the same amount. This method can be applied to dried blood spots and may thus be useful in forensic medicine to provide basic anthropometrical measures for an individual based on a biological evidence sample.

  10. Optimal first trimester preeclampsia prediction: a comparison of multimarker algorithm, risk profiles and their sequential application.

    Science.gov (United States)

    Gabbay-Benziv, R; Oliveira, N; Baschat, A A

    2016-01-01

    To compare performance of multimarker algorithm, risk profiles and their sequential application in prediction of preeclampsia and determining potential intervention targets. Maternal characteristics, ultrasound variables and serum biomarkers were collected prospectively at first trimester. Univariate analysis identified preeclampsia associated variables followed by logistic regression analysis to determine the prediction rule. Combined characteristics of the cardiovascular, metabolic and the personal risk factors were compared to the multimarker algorithm and the sequential application of both methods. Out of 2433 women, 108 developed preeclampsia (4.4%). Probability scores considering nulliparity, prior preeclampsia, body mass index, diastolic blood pressure and placental growth factor had an area under the receiver operating characteristic curve 0.784 (95% CI = 0.721-0.847). While the multimarker algorithm had the lowest false negative rate, sequential application of cardiovascular and metabolic risk profiles in screen positives reduced false positives by 26% and identified blood pressure and metabolic risk in 49/54 (91%) women with subsequent preeclampsia as treatable risk factors. Sequential application of a multimarker algorithm followed by determination of treatable risk factors in screen positive women is the optimal approach for first trimester preeclampsia prediction and identification of women that may benefit from targeted metabolic or cardiovascular treatment. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  11. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children

    Science.gov (United States)

    Gilchrist, James J.; Heath, Jennifer N.; Msefula, Chisomo L.; Gondwe, Esther N.; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M.; Molyneux, Elizabeth M.; Graham, Stephen M.; Drayson, Mark T.; Molyneux, Malcolm E.

    2016-01-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  12. Response-predictive gene expression profiling of glioma progenitor cells in vitro.

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    Sylvia Moeckel

    Full Text Available High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a to enrich specimens for brain tumor initiating cells and (b to confront cells with a therapeutic agent before expression profiling.As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

  13. [Clinical profiles of patients with uncomplicated Plasmodum falciparum malaria in northwestern Colombia].

    Science.gov (United States)

    Knudson, Angélica; Nicholls, Rubén Santiago; Guerra, Angela Patricia; Sánchez, Ricardo

    2007-12-01

    Few studies describe the clinical presentations of uncomplicated Plasmodium falciparum malaria in the province of Córdoba in an endemic area of northwestern Colombia. Profiles of patients with uncomplicated Plasmodium falciparum malaria were described from two twons of Córdoba, Tierrata and Puerto Libertador, based on clinical, epidemiological and laboratory variables. Patients were examined according to standard WHO/PAHO protocols for assessment of antimalarial drug efficacy. Clinical data and parasitological information was collected as well. A multiple correspondence multivariate analysis was used to compare the profiles of 127 patients with uncomplicated Plasmodium falciparum malaria. Of the 127 patients,105 completed the 14-day follow-up and 7 had adequate clinical response. Between 80% and 98% of patients exhibited at least one of the most frequent symptoms of uncomplicated malaria, and 80.3% had asthenia as the most frequent symptom. The multivariate analysis grouped the variables into five distinguishable clusters of clinical profiles. These groups showed similarities with the classical clinical descriptions of uncomplicated malaria encountered in the literature. The low frequency of patients with adequate clinical response hampered the association analysis. In Córdoba, therapeutic failure to chloroquine treatment is high in treating uncomplicated Plasmodium falciparum malaria. Multivariate analysis summarized variables related to epidemiological and clinical aspects and permitted a more objective approach to the interpretation of the findings.

  14. A probabilistic model to predict clinical phenotypic traits from genome sequencing.

    Directory of Open Access Journals (Sweden)

    Yun-Ching Chen

    2014-09-01

    Full Text Available Genetic screening is becoming possible on an unprecedented scale. However, its utility remains controversial. Although most variant genotypes cannot be easily interpreted, many individuals nevertheless attempt to interpret their genetic information. Initiatives such as the Personal Genome Project (PGP and Illumina's Understand Your Genome are sequencing thousands of adults, collecting phenotypic information and developing computational pipelines to identify the most important variant genotypes harbored by each individual. These pipelines consider database and allele frequency annotations and bioinformatics classifications. We propose that the next step will be to integrate these different sources of information to estimate the probability that a given individual has specific phenotypes of clinical interest. To this end, we have designed a Bayesian probabilistic model to predict the probability of dichotomous phenotypes. When applied to a cohort from PGP, predictions of Gilbert syndrome, Graves' disease, non-Hodgkin lymphoma, and various blood groups were accurate, as individuals manifesting the phenotype in question exhibited the highest, or among the highest, predicted probabilities. Thirty-eight PGP phenotypes (26% were predicted with area-under-the-ROC curve (AUC>0.7, and 23 (15.8% of these were statistically significant, based on permutation tests. Moreover, in a Critical Assessment of Genome Interpretation (CAGI blinded prediction experiment, the models were used to match 77 PGP genomes to phenotypic profiles, generating the most accurate prediction of 16 submissions, according to an independent assessor. Although the models are currently insufficiently accurate for diagnostic utility, we expect their performance to improve with growth of publicly available genomics data and model refinement by domain experts.

  15. Cardiovascular regulation profile predicts developmental trajectory of BMI and pediatric obesity.

    Science.gov (United States)

    Graziano, Paulo A; Calkins, Susan D; Keane, Susan P; O'Brien, Marion

    2011-09-01

    The present study examined the role of cardiovascular regulation in predicting pediatric obesity. Participants for this study included 268 children (141 girls) obtained from a larger ongoing longitudinal study. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (vagal withdrawal) to three cognitively challenging tasks were derived when children were 5.5 years of age. Heart period (HP) and HP change (heart rate (HR) acceleration) were also examined. Height and weight measures were collected when children were 5.5, 7.5, and 10.5 years of age. Results indicated that physiological regulation at age 5.5 was predictive of both normal variations in BMI development and pediatric obesity at age 10.5. Specifically, children with a cardiovascular regulation profile characterized by lower levels of RSA suppression and HP change experienced significantly greater levels of BMI growth and were more likely to be classified as overweight/at-risk for overweight at age 10.5 compared to children with a cardiovascular regulation profile characterized by high levels of RSA suppression and HP change. However, a significant interaction with racial status was found suggesting that the association between cardiovascular regulation profile and BMI growth and pediatric obesity was only significant for African-American children. An autonomic cardiovascular regulation profile consisting of low parasympathetic activity represents a significant individual risk factor for the development of pediatric obesity, but only for African-American children. Mechanisms by which early physiological regulation difficulties may contribute to the development of pediatric obesity are discussed.

  16. The idiopathic intracranial hypertension treatment trial: clinical profile at baseline.

    Science.gov (United States)

    Wall, Michael; Kupersmith, Mark J; Kieburtz, Karl D; Corbett, James J; Feldon, Steven E; Friedman, Deborah I; Katz, David M; Keltner, John L; Schron, Eleanor B; McDermott, Michael P

    2014-06-01

    To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between -2 dB and -7 dB. All but 4 participants were women. Baseline and laboratory characteristics. The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was -3.5 (1.1) dB, (range, -2.0 to -6.4 dB) and in the best eye was -2.3 (1.1) dB (range, -5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire-25 and the Short Form-36 physical and mental health summary scales, were lower compared with population norms. The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may

  17. Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.

    Directory of Open Access Journals (Sweden)

    Sean P Pitroda

    Full Text Available Vascular endothelial cells contribute to the pathogenesis of numerous human diseases by actively regulating the stromal inflammatory response; however, little is known regarding the role of endothelial inflammation in the growth of human tumors and its influence on the prognosis of human cancers.Using an experimental model of tumor necrosis factor-alpha (TNF-α-mediated inflammation, we characterized inflammatory gene expression in immunopurified tumor-associated endothelial cells. These genes formed the basis of a multivariate molecular predictor of overall survival that was trained and validated in four types of human cancer.We report that expression of experimentally derived tumor endothelial genes distinguished pathologic tissue specimens from normal controls in several human diseases associated with chronic inflammation. We trained these genes in human cancer datasets and defined a six-gene inflammatory signature that predicted significantly reduced overall survival in breast cancer, colon cancer, lung cancer, and glioma. This endothelial-derived signature predicted outcome independently of, but cooperatively with, standard clinical and pathological prognostic factors. Consistent with these findings, conditioned culture media from human endothelial cells stimulated by pro-inflammatory cytokines accelerated the growth of human colon and breast tumors in immunodeficient mice as compared with conditioned media from untreated endothelial cells.This study provides the first prognostic cancer gene signature derived from an experimental model of tumor-associated endothelial inflammation. These findings support the notion that activation of inflammatory pathways in non-malignant tumor-infiltrating endothelial cells contributes to tumor growth and progression in multiple human cancers. Importantly, these results identify endothelial-derived factors that could serve as potential targets for therapy in diverse human cancers.

  18. A portal dosimetry dose prediction method based on collapsed cone algorithm using the clinical beam model.

    Science.gov (United States)

    Martínez Ortega, J; Gómez González, N; Castro Tejero, P; Pinto Monedero, M; Tolani, N B; Núñez Martín, L; Sánchez Montero, R

    2017-01-01

    Amorphous silicon electronical portal imaging devices (EPIDs) are widely used for dosimetric measurements in Radiation Therapy. The purpose of this work was to determine if a portal dose prediction method can be utilized for dose map calculations based on the linear accelerator model within a commercial treatment planning system (Pinnacle 3 v8.0 m). The method was developed for a 6 MV photon beam on the Varian Clinac 21-EX, at a nominal dose rate of 400 MU/min. The Varian aS1000 EPID was unmounted from the linear accelerator and scanned to acquire CT images of the EPID. The CT images were imported into Pinnacle 3 and were used as a quality assurance phantom to calculate dose on the EPID setup at a source to detector distance of 105 cm. The best match of the dose distributions was obtained considering the image plane located at 106 cm from the source to detector plane. The EPID was calibrated according to the manufacturer procedure and corrections were made for output factors. Arm-backscattering effect, based on profile correction curves, has been introduced. Five low-modulated and three high-modulated clinical planned treatments were predicted and measured with the method presented here and with MatriXX (IBA Dosimetry, Schwarzenbruck, Germany). A portal dose prediction method based on Pinnacle 3 was developed without modifying the commissioned parameters of the model in use in the clinic. CT images of the EPID were acquired and used as a quality assurance phantom. The CT images indicated a mean density of 1.16 g/cm 3 for the sensitive area of the EPID. Output factor measured with the EPID were lower for small fields and larger for larger fields (beyond 10 × 10 cm 2 ). Arm-backscatter correction showed a better agreement at the target side of the EPID. Analysis of Gamma index comparison (3%, 3 mm) indicated a minimum of 97.4% pass rate for low modulated and 98.3% for high modulated treatments. Pass rates were similar for MatriXX measurements. The method

  19. Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress.

    Science.gov (United States)

    Larrieu, Thomas; Cherix, Antoine; Duque, Aranzazu; Rodrigues, João; Lei, Hongxia; Gruetter, Rolf; Sandi, Carmen

    2017-07-24

    Extensive data highlight the existence of major differences in individuals' susceptibility to stress [1-4]. While genetic factors [5, 6] and exposure to early life stress [7, 8] are key components for such neurobehavioral diversity, intriguing observations revealed individual differences in response to stress in inbred mice [9-12]. This raised the possibility that other factors might be critical in stress vulnerability. A key challenge in the field is to identify non-invasively risk factors for vulnerability to stress. Here, we investigated whether behavioral factors, emerging from preexisting dominance hierarchies, could predict vulnerability to chronic stress [9, 13-16]. We applied a chronic social defeat stress (CSDS) model of depression in C57BL/6J mice to investigate the predictive power of hierarchical status to pinpoint which individuals will exhibit susceptibility to CSDS. Given that the high social status of dominant mice would be the one particularly challenged by CSDS, we predicted and found that dominant individuals were the ones showing a strong susceptibility profile as indicated by strong social avoidance following CSDS, while subordinate mice were not affected. Data from (1)H-NMR spectroscopy revealed that the metabolic profile in the nucleus accumbens (NAc) relates to social status and vulnerability to stress. Under basal conditions, subordinates show lower levels of energy-related metabolites compared to dominants. In subordinates, but not dominants, levels of these metabolites were increased after exposure to CSDS. To the best of our knowledge, this is the first study that identifies non-invasively the origin of behavioral risk factors predictive of stress-induced depression-like behaviors associated with metabolic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Predictive factors of clinical outcome in older surgical patients.

    Science.gov (United States)

    Bo, Mario; Cacello, Elena; Ghiggia, Federica; Corsinovi, Laura; Bosco, Francesca

    2007-01-01

    We aimed to identify predictors of mortality and length of stay-in hospital in older surgical patients. In 294 patients (mean age 74.1+/-6.4 years, 153 men), consecutively admitted to four surgery units of a university-teaching hospital to receive elective surgery (ES, 56.5%) or urgent surgery (US, 43.5%), the following variables were evaluated: demographics, clinical history (hypertension, diabetes mellitus (DM), coronary heart disease (CHD), heart failure (HF), cerebrovascular accidents, chronic obstructive pulmonary disease (COPD), active neoplasm, cognitive impairment, immobilization, pressure ulcers), physiopathology (Acute Physiology and Chronic Health Evaluation, APACHE, II), cognition/function (Short Portable Mental Status Questionnaire, SPMSQ; activity of daily living, ADL; instrumental activity of daily living, IADL), comorbidity (Cumulative Illness Rating Scale, CIRS, 1 and 2) and anesthesiology (American Score Anesthesiologist, ASA). The vital status of the patient at 1 month after discharge and the duration of hospitalization were recorded. One-month mortality rate was 6.1%. Low hemoglobin and body mass index (BMI) values, increasing ASA score, and, only in US patients, ADL dependence and higher CIRS 1 score, were independently predictive of mortality. Low hemoglobin levels and, only in ES patients, higher CIRS 1 score were associated with prolonged hospitalization. Prognostic indicators specific to older people have limited value in mortality models in elderly surgical patients.

  1. A study of the clinical profile and outcome of spina bifida

    OpenAIRE

    Theophilus Nikita Kumar; Ramesh M.K

    2016-01-01

    Neural tube defects (NTDs) are a group of congenital anomalies characterized by defects in dorsal midline structures, including neural tissue, dura, muscle, bone and/or skin. The clinical presentations and the follow-up of these patients requires attention to various end organs besides the nervous system. To evaluate the clinical profile and surgical outcome of children with spina bifida. Out of a total of 74 patients treated at our institute for spina bifida between June 2013 to ...

  2. Profiles of Dispositional Expectancies and Affectivity Predict Later Psychosocial Functioning in Children and Adolescents With Cancer.

    Science.gov (United States)

    Okado, Yuko; Howard Sharp, Katianne M; Tillery, Rachel; Long, Alanna M; Phipps, Sean

    2016-04-01

    Examined how individual differences in disposition among pediatric cancer patients predict their later psychosocial functioning. Patients aged 8-17 years (N = 223) reported on their disposition at baseline. One and three years later, self-reports and parent reports of patient psychosocial functioning were obtained. Latent profile analysis was used to identify subgroups that differed on baseline disposition and to compare them on later outcomes. Three groups were identified: The "Positive" group (59%) had high optimism and positive affectivity and low pessimism and negative affectivity; the "Moderate" group (39%) had a similar profile, with less exaggerated scores; a small, "Negative" group (2%) had the opposite profile (low optimism/positive affectivity; high pessimism/negative affectivity). These groups differed in psychosocial functioning at follow-up, generally in expected directions. Most patients have a disposition that may be protective. A small minority at high risk for maladjustment is distinguished by their disposition. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Prediction of mitochondrial protein function by comparative physiology and phylogenetic profiling.

    Science.gov (United States)

    Cheng, Yiming; Perocchi, Fabiana

    2015-01-01

    According to the endosymbiotic theory, mitochondria originate from a free-living alpha-proteobacteria that established an intracellular symbiosis with the ancestor of present-day eukaryotic cells. During the bacterium-to-organelle transformation, the proto-mitochondrial proteome has undergone a massive turnover, whereby less than 20 % of modern mitochondrial proteomes can be traced back to the bacterial ancestor. Moreover, mitochondrial proteomes from several eukaryotic organisms, for example, yeast and human, show a rather modest overlap, reflecting differences in mitochondrial physiology. Those differences may result from the combination of differential gain and loss of genes and retargeting processes among lineages. Therefore, an evolutionary signature, also called "phylogenetic profile", could be generated for every mitochondrial protein. Here, we present two evolutionary biology approaches to study mitochondrial physiology: the first strategy, which we refer to as "comparative physiology," allows the de novo identification of mitochondrial proteins involved in a physiological function; the second, known as "phylogenetic profiling," allows to predict protein functions and functional interactions by comparing phylogenetic profiles of uncharacterized and known components.

  4. Multimarker proteomic profiling for the prediction of cardiovascular mortality in patients with chronic heart failure.

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    Gilles Lemesle

    Full Text Available Risk stratification of patients with systolic chronic heart failure (HF is critical to better identify those who may benefit from invasive therapeutic strategies such as cardiac transplantation. Proteomics has been used to provide prognostic information in various diseases. Our aim was to investigate the potential value of plasma proteomic profiling for risk stratification in HF. A proteomic profiling using surface enhanced laser desorption ionization - time of flight - mass spectrometry was performed in a case/control discovery population of 198 patients with systolic HF (left ventricular ejection fraction <45%: 99 patients who died from cardiovascular cause within 3 years and 99 patients alive at 3 years. Proteomic scores predicting cardiovascular death were developed using 3 regression methods: support vector machine, sparse partial least square discriminant analysis, and lasso logistic regression. Forty two ion m/z peaks were differentially intense between cases and controls in the discovery population and were used to develop proteomic scores. In the validation population, score levels were higher in patients who subsequently died within 3 years. Similar areas under the curves (0.66 - 0.68 were observed for the 3 methods. After adjustment on confounders, proteomic scores remained significantly associated with cardiovascular mortality. Use of the proteomic scores allowed a significant improvement in discrimination of HF patients as determined by integrated discrimination improvement and net reclassification improvement indexes. In conclusion, proteomic analysis of plasma proteins may help to improve risk prediction in HF patients.

  5. Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants.

    Science.gov (United States)

    van Ganzewinkel, C; Derijks, L; Anand, K J S; van Lingen, R A; Neef, C; Kramer, B W; Andriessen, P

    2014-06-01

    The therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present pharmacokinetics after multiple dose of intravenous paracetamol in very preterm infants of paracetamol (7.5 mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. A two-compartment pharmacokinetic model gave the best fit for all individual patients and resulted in a predictable pharmacokinetic profile. The estimated pharmacokinetic population parameters were volume of distribution 0.764 ± 0.225 L/kg, elimination rate constant (ke ) 0.117 ± 0.091/h and intercompartment rate constants k12 0.607 ± 0.734/h and k21 1.105 ± 0.762/h. Our study found that multiple doses of intravenous paracetamol resulted in a predictable pharmacokinetic profile in very preterm infants. Increases in postmenstrual age and weight were associated with increased clearance. No evidence of hepatotoxicity was found. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  6. How good are publicly available web services that predict bioactivity profiles for drug repurposing?

    Science.gov (United States)

    Murtazalieva, K A; Druzhilovskiy, D S; Goel, R K; Sastry, G N; Poroikov, V V

    2017-10-01

    Drug repurposing provides a non-laborious and less expensive way for finding new human medicines. Computational assessment of bioactivity profiles shed light on the hidden pharmacological potential of the launched drugs. Currently, several freely available computational tools are available via the Internet, which predict multitarget profiles of drug-like compounds. They are based on chemical similarity assessment (ChemProt, SuperPred, SEA, SwissTargetPrediction and TargetHunter) or machine learning methods (ChemProt and PASS). To compare their performance, this study has created two evaluation sets, consisting of (1) 50 well-known repositioned drugs and (2) 12 drugs recently patented for new indications. In the first set, sensitivity values varied from 0.64 (TarPred) to 1.00 (PASS Online) for the initial indications and from 0.64 (TarPred) to 0.98 (PASS Online) for the repurposed indications. In the second set, sensitivity values varied from 0.08 (SuperPred) to 1.00 (PASS Online) for the initial indications and from 0.00 (SuperPred) to 1.00 (PASS Online) for the repurposed indications. Thus, this analysis demonstrated that the performance of machine learning methods surpassed those of chemical similarity assessments, particularly in the case of novel repurposed indications.

  7. Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction

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    Vania C. Liuzzi

    2017-01-01

    Full Text Available Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA and enniatins (ENNs. Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1 that contains both peptide synthetase and S-adenosyl-l-methionine-dependent N-methyltransferase activities. Several Fusarium species can produce ENNs, BEA or both, but the mechanism(s enabling these differential metabolic profiles is unknown. In this study, we analyzed the primary structure of ESYN1 by sequencing esyn1 transcripts from different Fusarium species. We measured ENNs and BEA production by ultra-performance liquid chromatography coupled with photodiode array and Acquity QDa mass detector (UPLC-PDA-QDa analyses. We predicted protein structures, compared the predictions by multivariate analysis methods and found a striking correlation between BEA/ENN-producing profiles and ESYN1 three-dimensional structures. Structural differences in the β strand’s Asn789-Ala793 and His797-Asp802 portions of the amino acid adenylation domain can be used to distinguish BEA/ENN-producing Fusarium isolates from those that produce only ENN.

  8. Characterisation of linear predictability and non-stationarity of subcutaneous glucose profiles.

    Science.gov (United States)

    Khovanova, N A; Khovanov, I A; Sbano, L; Griffiths, F; Holt, T A

    2013-06-01

    Continuous glucose monitoring is increasingly used in the management of diabetes. Subcutaneous glucose profiles are characterised by a strong non-stationarity, which limits the application of correlation-spectral analysis. We derived an index of linear predictability by calculating the autocorrelation function of time series increments and applied detrended fluctuation analysis to assess the non-stationarity of the profiles. Time series from volunteers with both type 1 and type 2 diabetes and from control subjects were analysed. The results suggest that in control subjects, blood glucose variation is relatively uncorrelated, and this variation could be modelled as a random walk with no retention of 'memory' of previous values. In diabetes, variation is both greater and smoother, with retention of inter-dependence between neighbouring values. Essential components for adequate longer term prediction were identified via a decomposition of time series into a slow trend and responses to external stimuli. Implications for diabetes management are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Anthropometric profile of elite acrobatic gymnasts and prediction of role performance.

    Science.gov (United States)

    Taboada-Iglesias, Yaiza; Gutiérrez-Sánchez, Águeda; Vernetta Santana, Mercedes

    2016-04-01

    This study is aimed at determining the anthropometric profile of acrobatic gymnasts, differentiating on the basis of their role. The sample consisted of 150 gymnasts (129 women and 21 men) from throughout Spain. The anthropometric measurements were taken according to the International Society for the Advancement of Kinanthropometry (ISAK) procedures. Morphological measurements, proportionality and somatotype were analyzed in both groups. A comparative analysis between groups and a prediction model were used to analyze the specific profile of each role. All morphological measurements showed significant differences (Pendomorphic element of the bases presented higher values than the tops, for whom the ectomorphy scores were higher. Bases have an endo-mesomorphic somatotype and tops present a balanced mesomorphic. There are no mesomorphy differences between the tops and bases. BMI was significantly higher in the bases (BMI=20.28 kg/m2). Proportionality differences between roles are shown. Both roles present negatives values for almost all variables studied except for the trochlear condyle of the humerus, the bicondyle of the femur and the wrist bistyloid breadth in tops and the wrist bistyloid breadth, the upper arm relaxed girths and maximum calf in bases. The best prediction model included thigh girth as the best explanatory covariate of role performance. Here are differences between both roles, bases being gymnasts of larger size than tops. However, they present no differences in the muscular component, as it might be expected.

  10. Identification of a kinase profile that predicts chromosome damage induced by small molecule kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Andrew J Olaharski

    2009-07-01

    Full Text Available Kinases are heavily pursued pharmaceutical targets because of their mechanistic role in many diseases. Small molecule kinase inhibitors (SMKIs are a compound class that includes marketed drugs and compounds in various stages of drug development. While effective, many SMKIs have been associated with toxicity including chromosomal damage. Screening for kinase-mediated toxicity as early as possible is crucial, as is a better understanding of how off-target kinase inhibition may give rise to chromosomal damage. To that end, we employed a competitive binding assay and an analytical method to predict the toxicity of SMKIs. Specifically, we developed a model based on the binding affinity of SMKIs to a panel of kinases to predict whether a compound tests positive for chromosome damage. As training data, we used the binding affinity of 113 SMKIs against a representative subset of all kinases (290 kinases, yielding a 113x290 data matrix. Additionally, these 113 SMKIs were tested for genotoxicity in an in vitro micronucleus test (MNT. Among a variety of models from our analytical toolbox, we selected using cross-validation a combination of feature selection and pattern recognition techniques: Kolmogorov-Smirnov/T-test hybrid as a univariate filter, followed by Random Forests for feature selection and Support Vector Machines (SVM for pattern recognition. Feature selection identified 21 kinases predictive of MNT. Using the corresponding binding affinities, the SVM could accurately predict MNT results with 85% accuracy (68% sensitivity, 91% specificity. This indicates that kinase inhibition profiles are predictive of SMKI genotoxicity. While in vitro testing is required for regulatory review, our analysis identified a fast and cost-efficient method for screening out compounds earlier in drug development. Equally important, by identifying a panel of kinases predictive of genotoxicity, we provide medicinal chemists a set of kinases to avoid when designing

  11. Clinical and medication profiles stratified by household income in patients referred for diabetes care

    Directory of Open Access Journals (Sweden)

    Svenson Lawrence W

    2007-03-01

    Full Text Available Abstract Background Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles. Methods This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses. Results Multivariate regression analysis indicated that income was negatively associated with BMI (p Conclusion Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.

  12. Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC/MS technology.

    Science.gov (United States)

    Li, Y; Xu, C; Xia, C; Zhang, Hy; Sun, Lw; Gao, Y

    2014-01-01

    Ketosis in dairy cattle is an important metabolic disorder. Currently, the plasma metabolic profile of ketosis as determined using liquid chromatography-mass spectrometry (LC/MS) has not been reported. To investigate plasma metabolic profiles from cows with clinical ketosis in comparison to control cows. Twenty Holstein dairy cows were divided into two groups based on clinical signs and plasma β-hydroxybutyric acid and glucose concentrations 7-21 days postpartum: clinical ketosis and control cows. Plasma metabolic profiles were analyzed using LC/MS. Data were processed using principal component analysis and orthogonal partial least-squares discriminant analysis. Compared to control cows, the levels of valine, glycine, glycocholic, tetradecenoic acid, and palmitoleic acid increased significantly in clinical ketosis. On the other hand, the levels of arginine, aminobutyric acid, leucine/isoleucine, tryptophan, creatinine, lysine, norcotinine, and undecanoic acid decreased markedly. Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

  13. A behavioral and cognitive profile of clinically stable HIV-infected children

    NARCIS (Netherlands)

    Nozyce, ML; Lee, SS; Wiznia, A; Nachman, S; Mofenson, LM; Smith, ME; Yogev, R; McIntosh, K; Stanley, K; Pelton, S

    OBJECTIVE. The purpose of this research was to characterize behavioral and cognitive profiles of clinically and immunologically stable antiretroviral-experienced HIV-infected children. METHODS. Two hundred seventy-four previously treated HIV-infected children aged 2 to 17 years were assessed for

  14. Phonetogram voice range profile : assessment of voice capacities and its clinical value

    NARCIS (Netherlands)

    Schutte, HK; Clements, MP

    1996-01-01

    Voice range profile measurement is being used more and more as a practical clinical tool in the process of voice evaluation. In principle it means a graphical representation of a patient's or person's vocal capabilities concerning the fundamental frequency range and dynamic range on several

  15. Induction of labour: clinical predictive factors for success and failure.

    Science.gov (United States)

    Batinelli, Laura; Serafini, Andrea; Nante, Nicola; Petraglia, Felice; Severi, Filiberto Maria; Messina, Gabriele

    2017-10-23

    literature that 'multiparity' and 'Bishop score' are linked with the success of IOL and adds that 'maternal age' and 'foetal birth weight' are significant risk factors for the population of uncomplicated post term pregnancies induced with prostaglandins. What the implications are of these findings for clinical practice and/or further research: Our results agreed with the existing literature regarding parity and Bishop score but not for maternal age and birth weight. This adds new precious data to the literature which could be used for systematic reviews and for implementing IOL guidelines and protocols, nationally and internationally. Our findings could be also used for guiding future research in this field. It will be interesting to investigate the existence of not just specific factors but also any combination of variables which could predict the success of the procedure. At the moment these information cannot be used in terms of decision making for healthcare professionals as no variable is 100% predictive but once further research will be added, we may be able to know when is best time to start the IOL, how to facilitate the success of the procedure and how to best support the woman throughout the whole experience.

  16. Predicting Mental Imagery-Based BCI Performance from Personality, Cognitive Profile and Neurophysiological Patterns.

    Directory of Open Access Journals (Sweden)

    Camille Jeunet

    Full Text Available Mental-Imagery based Brain-Computer Interfaces (MI-BCIs allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy-EEG, which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants' BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants' performance with a mean error of less than 3 points. This study determined how users' profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user.

  17. Predicting Mental Imagery-Based BCI Performance from Personality, Cognitive Profile and Neurophysiological Patterns.

    Science.gov (United States)

    Jeunet, Camille; N'Kaoua, Bernard; Subramanian, Sriram; Hachet, Martin; Lotte, Fabien

    2015-01-01

    Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy-EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants' BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants' performance with a mean error of less than 3 points. This study determined how users' profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user.

  18. Rorschach Prediction of Success in Clinical Training: A Second Look

    Science.gov (United States)

    Carlson, Rae

    1969-01-01

    A Rorschach Index based on ego-psychological conceptualization of an optimal personality picture predicted for 155 trainees was compared with predictions from the Miller Analogies Test (MAT) and the Strong Vocational Interest Blank (SVIB). The Index predicted success and failure more effectively. (Author)

  19. (1)H-Nuclear magnetic resonance-based plasma metabolic profiling of dairy cows with clinical and subclinical ketosis.

    Science.gov (United States)

    Sun, L W; Zhang, H Y; Wu, L; Shu, S; Xia, C; Xu, C; Zheng, J S

    2014-03-01

    The purpose of this study was to assess the metabolic profile of plasma samples from cows with clinical and subclinical ketosis. According to clinical signs and 3-hydroxybutyrate plasma levels, 81 multiparous Holstein cows were selected from a dairy farm 7 to 21 d after calving. The cows were divided into 3 groups: cows with clinical ketosis, cows with subclinical ketosis, and healthy control cows. (1)H-Nuclear magnetic resonance-based metabolomics was used to assess the plasma metabolic profiles of the 3 groups. The data were analyzed by principal component analysis, partial least squares discriminant analysis, and orthogonal partial least-squares discriminant analysis. The differences in metabolites among the 3 groups were assessed. The orthogonal partial least-squares discriminant analysis model differentiated the 3 groups of plasma samples. The model predicted clinical ketosis with a sensitivity of 100% and a specificity of 100%. In the case of subclinical ketosis, the model had a sensitivity of 97.0% and specificity of 95.7%. Twenty-five metabolites, including acetoacetate, acetone, lactate, glucose, choline, glutamic acid, and glutamine, were different among the 3 groups. Among the 25 metabolites, 4 were upregulated, 7 were downregulated, and 14 were both upregulated and downregulated. The results indicated that plasma (1)H-nuclear magnetic resonance-based metabolomics, coupled with pattern recognition analytical methods, not only has the sensitivity and specificity to distinguish cows with clinical and subclinical ketosis from healthy controls, but also has the potential to be developed into a clinically useful diagnostic tool that could contribute to a further understanding of the disease mechanisms. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Electromyographic Patterns during Golf Swing: Activation Sequence Profiling and Prediction of Shot Effectiveness

    Directory of Open Access Journals (Sweden)

    Antanas Verikas

    2016-04-01

    Full Text Available This study analyzes muscle activity, recorded in an eight-channel electromyographic (EMG signal stream, during the golf swing using a 7-iron club and exploits information extracted from EMG dynamics to predict the success of the resulting shot. Muscles of the arm and shoulder on both the left and right sides, namely flexor carpi radialis, extensor digitorum communis, rhomboideus and trapezius, are considered for 15 golf players (∼5 shots each. The method using Gaussian filtering is outlined for EMG onset time estimation in each channel and activation sequence profiling. Shots of each player revealed a persistent pattern of muscle activation. Profiles were plotted and insights with respect to player effectiveness were provided. Inspection of EMG dynamics revealed a pair of highest peaks in each channel as the hallmark of golf swing, and a custom application of peak detection for automatic extraction of swing segment was introduced. Various EMG features, encompassing 22 feature sets, were constructed. Feature sets were used individually and also in decision-level fusion for the prediction of shot effectiveness. The prediction of the target attribute, such as club head speed or ball carry distance, was investigated using random forest as the learner in detection and regression tasks. Detection evaluates the personal effectiveness of a shot with respect to the player-specific average, whereas regression estimates the value of target attribute, using EMG features as predictors. Fusion after decision optimization provided the best results: the equal error rate in detection was 24.3% for the speed and 31.7% for the distance; the mean absolute percentage error in regression was 3.2% for the speed and 6.4% for the distance. Proposed EMG feature sets were found to be useful, especially when used in combination. Rankings of feature sets indicated statistics for muscle activity in both the left and right body sides, correlation-based analysis of EMG

  1. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  2. CDMS (Clinical Data Mining Software): a cytokinome data mining system for a predictive medicine of chronic inflammatory diseases

    National Research Council Canada - National Science Library

    Evangelista, D; Colonna, G; Miele, M; Cutugno, F; Castello, G; Desantis, S; Costantini, S

    2010-01-01

    .... We developed a Clinical Data Mining Software to collect cytokine profiles evaluated on healthy subjects and patients by multiplex immunoassays also annotated with their clinical and laboratory data...

  3. Secondary progressive multiple sclerosis - clinical course and potential predictive factors.

    Science.gov (United States)

    Pokryszko-Dragan, Anna; Gruszka, Ewa; Bilińska, Małgorzata; Dubik-Jezierzańska, Marta

    2008-01-01

    To characterize the course of secondary progressive multiple sclerosis (SPMS), with an attempt to assess the predictive value of early clinical variables. Medical records of 100 patients with SPMS (40 men, 60 women, aged 34-73) were analyzed retrospectively. Age at onset of MS, first symptoms, annual exacerbation rate (AER), time to progressive phase (TTP), degree of disability at its beginning (Expanded Disability Status Scale; EDSS SP), and annual progression in disability in relapsing-remitting and progressive phases (APD RR and APD SP) were compared for the gender subgroups, and the relationships between them were analyzed. Time to progressive phase range was 2-29 years (mean 11.51) and EDSS SP 2-7.5 (mean 5.55). Time to progressive phase in women was longer and EDSS SP was lower than in men. Age at onset of MS, AER and ADP RR correlated positively with TTP. Optic neuritis was the most common first symptom (49%; motor deficit and cerebellar/brainstem involvement 26% and 21%, respectively). Time to progressive phase in the former subgroup was shorter than in the latter, but no differences in ADP SP were found. Annual progression in disability in relapsing-remitting was higher than APD SP. Degree of disability at its beginning (EDSS SP) correlated negatively with ADP SP. Older age at onset, male gender, frequent relapses and fast increase in disability in the relapsing-remitting phase are risk factors for conversion to SPMS. Increase in disability during the progressive phase is slower than in the relapsing-remitting phase and depends mainly on initial EDSS. Individual variability of the course of MS has to be considered.

  4. Reproducibility of mass spectrometry based protein profiles for diagnosis of ovarian cancer across clinical studies

    DEFF Research Database (Denmark)

    Øgendahl Callesen, Anne Kjærgaard; Mogensen, Ole; Jensen, Andreas K

    2012-01-01

    The focus of this systematic review is to give an overview of the current status of clinical protein profiling studies using MALDI and SELDI MS platforms in the search for ovarian cancer biomarkers. A total of 34 profiling studies were qualified for inclusion in the review. Comparative analysis......, and data analysis. About 47% of the peaks reported to be associated to ovarian cancer were also represented in our experimental study, and 34% of these redetected peaks also showed a significant difference between cases and controls in our study. Thus, despite known problems related to reproducibility...... an overlap in peaks between clinical studies was demonstrated, which indicate convergence toward a set of common discriminating, reproducible peaks for ovarian cancer. The potential of the discriminating protein peaks for clinical use as ovarian cancer biomarkers will be discussed and evaluated. This article...

  5. TEMA and Dot Enumeration Profiles Predict Mental Addition Problem Solving Speed Longitudinally

    Directory of Open Access Journals (Sweden)

    Clare S. Major

    2017-12-01

    Full Text Available Different math indices can be used to assess math potential at school entry. We evaluated whether standardized math achievement (TEMA-2 performance, core number abilities (dot enumeration, symbolic magnitude comparison, non-verbal intelligence (NVIQ and visuo-spatial working memory (VSWM, in combination or separately, predicted mental addition problem solving speed over time. We assessed 267 children’s TEMA-2, magnitude comparison, dot enumeration, and VSWM abilities at school entry (5 years and NVIQ at 8 years. Mental addition problem solving speed was assessed at 6, 8, and 10 years. Longitudinal path analysis supported a model in which dot enumeration performance ability profiles and previous mental addition speed predicted future mental addition speed on all occasions, supporting a componential account of math ability. Standardized math achievement and NVIQ predicted mental addition speed at specific time points, while VSWM and symbolic magnitude comparison did not contribute unique variance to the model. The implications of using standardized math achievement and dot enumeration ability to index math learning potential at school entry are discussed.

  6. ECG dispersion mapping predicts clinical deterioration, measured by increase in the Simple Clinical Score.

    LENUS (Irish Health Repository)

    Kellett, J

    2012-01-01

    Objective: ECG dispersion mapping (ECG-DM) is a novel technique that reports abnormal ECG microalternations. We report the ability of ECG-DM to predict clinical deterioration of acutely ill medical patients, as measured by an increase in the Simple Clinical Score (SCS) the day after admission to hospital. Methods: 453 acutely ill medical patients (mean age 69.7 +\\/- 14.0 years) had the SCS recorded and ECGDM performed immediately after admission to hospital. Results: 46 patients had an SCS increase 20.8 +\\/- 7.6 hours after admission. Abnormal micro-alternations during left ventricular re-polarization had the highest association with SCS increase (p=0.0005). Logistic regression showed that only nursing home residence and abnormal micro-alternations during re-polarization of the left ventricle were independent predictors of SCS increase with an odds ratio of 2.84 and 3.01, respectively. Conclusion: ECG-DM changes during left ventricular re-polarization are independent predictors of clinical deterioration the day after hospital admission.

  7. An oracle: antituberculosis pharmacokinetics-pharmacodynamics, clinical correlation, and clinical trial simulations to predict the future.

    Science.gov (United States)

    Pasipanodya, Jotam; Gumbo, Tawanda

    2011-01-01

    Antimicrobial pharmacokinetic-pharmacodynamic (PK/PD) science and clinical trial simulations have not been adequately applied to the design of doses and dose schedules of antituberculosis regimens because many researchers are skeptical about their clinical applicability. We compared findings of preclinical PK/PD studies of current first-line antituberculosis drugs to findings from several clinical publications that included microbiologic outcome and pharmacokinetic data or had a dose-scheduling design. Without exception, the antimicrobial PK/PD parameters linked to optimal effect were similar in preclinical models and in tuberculosis patients. Thus, exposure-effect relationships derived in the preclinical models can be used in the design of optimal antituberculosis doses, by incorporating population pharmacokinetics of the drugs and MIC distributions in Monte Carlo simulations. When this has been performed, doses and dose schedules of rifampin, isoniazid, pyrazinamide, and moxifloxacin with the potential to shorten antituberculosis therapy have been identified. In addition, different susceptibility breakpoints than those in current use have been identified. These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration.

  8. CLINICAL DATABASE ANALYSIS USING DMDT BASED PREDICTIVE MODELLING

    Directory of Open Access Journals (Sweden)

    Srilakshmi Indrasenan

    2013-04-01

    Full Text Available In recent years, predictive data mining techniques play a vital role in the field of medical informatics. These techniques help the medical practitioners in predicting various classes which is useful in prediction treatment. One of such major difficulty is prediction of survival rate in breast cancer patients. Breast cancer is a common disease these days and fighting against it is a tough battle for both the surgeons and the patients. To predict the survivability rate in breast cancer patients which helps the medical practitioner to select the type of treatment a predictive data mining technique called Diversified Multiple Decision Tree (DMDT classification is used. Additionally, to avoid difficulties from the outlier and skewed data, it is also proposed to perform the improvement of training space by outlier filtering and over sampling. As a result, this novel approach gives the survivability rate of the cancer patients based on which the medical practitioners can choose the type of treatment.

  9. Latent profile analysis in frontotemporal lobar degeneration and related disorders: clinical presentation and SPECT functional correlates

    Directory of Open Access Journals (Sweden)

    Di Luca Monica

    2007-05-01

    Full Text Available Abstract Background Frontotemporal Lobar Degeneration (FTLD thus recently renamed, refers to a spectrum of heterogeneous conditions. This same heterogeneity of presentation represents the major methodological limit for the correct evaluation of clinical designation and brain functional correlates. At present, no study has investigated clinical clusters due to specific cognitive and behavioural disturbances beyond current clinical criteria. The aim of this study was to identify clinical FTLD presentation, based on cognitive and behavioural profile, and to define their SPECT functional correlations. Methods Ninety-seven FTLD patients entered the study. A clinical evaluation and standardised assessment were preformed, as well as a brain SPECT perfusion imaging study. Latent Profile Analysis on clinical, neuropsychological, and behavioural data was performed. Voxel-basis analysis of SPECT data was computed. Results Three specific clusters were identified and named "pseudomanic behaviour" (LC1, "cognitive" (LC2, and "pseudodepressed behaviour" (LC3 endophenotypes. These endophenotypes showed a comparable hypoperfusion in left temporal lobe, but a specific pattern involving: medial and orbitobasal frontal cortex in LC1, subcortical brain region in LC2, and right dorsolateral frontal cortex and insula in LC3. Conclusion These findings provide evidence that specific functional-cluster symptom relationship can be delineated in FTLD patients by a standardised assessment. The understanding of the different functional correlates of clinical presentations will hopefully lead to the possibility of individuating diagnostic and treatment algorithms.

  10. A novel method predicting clinical response using only background clinical data in RA patients before treatment with infliximab.

    Science.gov (United States)

    Miyoshi, Fumihiko; Honne, Kyoko; Minota, Seiji; Okada, Masato; Ogawa, Noriyoshi; Mimura, Toshihide

    2016-11-01

    The aim of the present study was to generate a novel method for predicting the clinical response to infliximab (IFX), using a machine-learning algorithm with only clinical data obtained before the treatment in rheumatoid arthritis (RA) patients. We obtained 32 variables out of the clinical data on the patients from two independent hospitals. Next, we selected both clinical parameters and machine-learning algorithms and decided the candidates of prediction method. These candidates were verified by clinical variables on different patients from two other hospitals. Finally, we decided the prediction method to achieve the highest score. The combination of multilayer perceptron algorithm (neural network) and nine clinical parameters shows the best accuracy performance. This method could predict the good or moderate response to IFX with 92% accuracy. The sensitivity of this method was 96.7%, while the specificity was 75%. We have developed a novel method for predicting the clinical response using only background clinical data in RA patients before treatment with IFX. Our method for predicting the response to IFX in RA patients may have advantages over the other previous methods in several points including easy usability, cost-effectiveness and accuracy.

  11. Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions.

    Science.gov (United States)

    Zhou, Weichen; Ma, Yanyun; Zhang, Jun; Hu, Jingyi; Zhang, Menghan; Wang, Yi; Li, Yi; Wu, Lijun; Pan, Yida; Zhang, Yitong; Zhang, Xiaonan; Zhang, Xinxin; Zhang, Zhanqing; Zhang, Jiming; Li, Hai; Lu, Lungen; Jin, Li; Wang, Jiucun; Yuan, Zhenghong; Liu, Jie

    2017-11-01

    Liver biopsy is the gold standard to assess pathological features (eg inflammation grades) for hepatitis B virus-infected patients although it is invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small hepatitis B virus (HBV)-infected samples. We aimed to analyse correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase and HBV-DNA) in large-scale CHB samples and to predict inflammation grades by using clinical parameters and/or gene expressions. We analysed gene expressions with three clinical parameters in 122 CHB samples by an improved regression model. Principal component analysis and machine-learning methods including Random Forest, K-nearest neighbour and support vector machine were used for analysis and further diagnosis models. Six normal samples were conducted to validate the predictive model. Significant genes related to clinical parameters were found enriching in the immune system, interferon-stimulated, regulation of cytokine production, anti-apoptosis, and etc. A panel of these genes with clinical parameters can effectively predict binary classifications of inflammation grade (area under the ROC curve [AUC]: 0.88, 95% confidence interval [CI]: 0.77-0.93), validated by normal samples. A panel with only clinical parameters was also valuable (AUC: 0.78, 95% CI: 0.65-0.86), indicating that liquid biopsy method for detecting the pathology of CHB is possible. This is the first study to systematically elucidate the relationships among gene expressions, clinical parameters and pathological inflammation grades in CHB, and to build models predicting inflammation grades by gene expressions and/or clinical parameters as well. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Clinical prediction of 5-year survival in systemic sclerosis

    DEFF Research Database (Denmark)

    Fransen, Julie Munk; Popa-Diaconu, D; Hesselstrand, R

    2011-01-01

    Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accura...

  13. Clinical Profile, Etiology, and Outcome of Infantile Ocular Trauma: A Developing Country Perspective.

    Science.gov (United States)

    Shah, Vedang D; Uddaraju, Madhu; Singh, Amitabh; Das, Rashmi Ranjan

    2017-06-20

    The aim of this article was to study the clinical profile, etiology, and outcome of infantile ocular trauma in a developing country setting. A retrospective study on corneal trauma in infants (≤12 months old) was undertaken in a tertiary care hospital during a 2-year period. An analysis of clinical profile, etiology, microbiological profile, clinical course, and outcome was studied. Seventy-six infants were included. Approximately 69% presented within 24 hours of injury. The common presentations were inability to open the eyelids, redness of eyes, and watering. Self-infliction by child's hand (49%) was found to be the main cause of corneal trauma. Corneal abrasion was seen in 34 cases (45%), isolated epithelial defects were seen in 30%, and infective keratitis was seen in 25%. Infection was found in 14 cases (fungal filaments in 7 and gram-positive cocci in 7). Only 36 infants followed up regularly in the hospital. All the infants following up in the hospital recovered in due course. Infantile ocular trauma is a common morbidity that is underreported. Self-infliction by child's hand was found to be the main cause of corneal trauma. Cases presenting early and following up regularly till recovery have a favorable clinical course with good outcome. A high loss to follow-up indicates that awareness needs to be created among the caregivers.

  14. Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples

    Directory of Open Access Journals (Sweden)

    Kamal Uddin Zaidi

    2016-01-01

    Full Text Available This study was done to assess the antifungal susceptibility of clinical isolates of Candida albicans and to evaluate its total protein profile based on morphological difference on drug resistance. Hundred and twenty clinical isolates of C. albicans from various clinical specimens were tested for susceptibility against four antifungal agents, namely, fluconazole, itraconazole, amphotericin B, and ketoconazole. A significant increase of drug resistance in clinical isolates of C. albicans was observed. The study showed 50% fluconazole and itraconazole resistance at 32 μg mL−1 with a MIC50 and MIC90 values at 34 and 47 and 36 and 49 μg mL−1, respectively. All isolates were sensitive to amphotericin B and ketoconazole. The SDS-PAGE protein profile showed a prevalent band of ~52.5 kDa, indicating overexpression of gene in 72% strains with fluconazole resistance. Since the opportunistic infections of Candida spp. are increasing along with drug resistance, the total protein profile will help in understanding the evolutionary changes in drug resistance and also to characterize them.

  15. Plasma Lipidomic Profiling of Treated HIV-Positive Individuals and the Implications for Cardiovascular Risk Prediction

    Science.gov (United States)

    Wong, Gerard; Trevillyan, Janine M.; Fatou, Benoit; Cinel, Michelle; Weir, Jacquelyn M.; Hoy, Jennifer F.; Meikle, Peter J.

    2014-01-01

    Background The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV- positive patients. Methods In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45). Results Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events. Conclusions Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients. PMID:24733512

  16. Plasma lipidomic profiling of treated HIV-positive individuals and the implications for cardiovascular risk prediction.

    Directory of Open Access Journals (Sweden)

    Gerard Wong

    Full Text Available BACKGROUND: The increased risk of coronary artery disease in human immunodeficiency virus (HIV positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV-positive patients. METHODS: In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23 were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD. They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45 and with healthy HIV-negative volunteers (n = 45. RESULTS: Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC of 0.78 (0.775, 0.785 and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events. CONCLUSIONS: Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients.

  17. Plasma lipidomic profiling of treated HIV-positive individuals and the implications for cardiovascular risk prediction.

    Science.gov (United States)

    Wong, Gerard; Trevillyan, Janine M; Fatou, Benoit; Cinel, Michelle; Weir, Jacquelyn M; Hoy, Jennifer F; Meikle, Peter J

    2014-01-01

    The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV-positive patients. In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45). Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events. Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients.

  18. Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling.

    Science.gov (United States)

    Lee, AeJin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

    2015-01-01

    Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome. In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit. We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (pObese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome. High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  19. Professional choice self-efficacy: predicting traits and personality profiles in high school students

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    Rodolfo Augusto Matteo Ambiel

    2016-01-01

    Full Text Available Abstract This study aimed to verify the predictive capacity of the Big Five personality factors related to professional choice self-efficacy, as well as to draw a personality profile of people with diverse self-efficacy levels. There were 308 high school students participating, from three different grades (57.5 % women, from public and private schools, average 26.64 years of age. Students completed two instruments, Escala de Autoeficácia para Escolha Profissional (Professional Choice Self-efficacy Scale and Bateria Fatorial de Personalidade (Factorial Personality Battery. Results were obtained using multiple regression analysis, analysis of variance with repeated measures profile and Cohen’s d to estimate the effect size of differences. Results showed that Extraversion, Agreeableness and Conscientiousness were the main predictors of self-efficacy. Differences from medium to large were observed between extreme groups, and Extraversion and Conscientiousness were the personality factors that better distinguish people with low and high levels of self-efficacy. Theses results partially corroborate with the hypothesis. Results were discussed based on literature and on the practical implications of the results. New studies are proposed.

  20. Mulligan Concept Use and Clinical Profile From the Perspective of American Certified Mulligan Practitioners.

    Science.gov (United States)

    May, James; Krzyzanowicz, Ryan; Nasypany, Alan; Seegmiller, Jeffrey

    2015-11-01

    Although randomized controlled trials indicate that the Mulligan Concept (MC) of mobilization with movement can improve pain-free grip strength and pressure pain threshold in patients with lateral epicondylalgia of the elbow, improve ankle dorsiflexion in patients with subacute ankle sprains, and decrease the signs and symptoms of patients with cervicogenic headache, little is known about the clinical application, use, and profile of certified Mulligan practitioners (CMPs) in America. To better understand the use and value of applying the MC philosophy in clinical-care environments from the perspective of American CMPs while establishing a clinical profile of a CMP. Quantitative descriptive design. Online survey instrument. American CMPs. Online survey instrument. CMPs use the MC to treat a broad spectrum of spinal and peripheral clinical pathologies in primarily outpatient clinics with an active and athletic population. American CMPs also find value in the MC. American CMPs continue to use and find value in the MC intervention strategy to treat a broad spectrum of spinal and peripheral conditions in their clinical practices.

  1. Disease-Specific Target Gene Expression Profiling of Molecular Imaging Probes: Database Development and Clinical Validation

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    Lawrence Wing-Chi Chan

    2014-08-01

    Full Text Available Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2- deoxy-2-D-glucose (FDG, respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/.

  2. Profiling the clinical presentation of diagnostic characteristics of a sample of symptomatic TMD patients

    Directory of Open Access Journals (Sweden)

    e Silva Machado Luciana

    2012-08-01

    Full Text Available Abstract Background Temporomandibular disorder (TMD patients might present a number of concurrent clinical diagnoses that may be clustered according to their similarity. Profiling patients’ clinical presentations can be useful for better understanding the behavior of TMD and for providing appropriate treatment planning. The aim of this study was to simultaneously classify symptomatic patients diagnosed with a variety of subtypes of TMD into homogenous groups based on their clinical presentation and occurrence of comorbidities. Methods Clinical records of 357 consecutive TMD patients seeking treatment in a private specialized clinic were included in the study sample. Patients presenting multiple subtypes of TMD diagnosed simultaneously were categorized according to the AAOP criteria. Descriptive statistics and two-step cluster analysis were used to characterize the clinical presentation of these patients based on the primary and secondary clinical diagnoses. Results The most common diagnoses were localized masticatory muscle pain (n = 125 and disc displacement without reduction (n = 104. Comorbidity was identified in 288 patients. The automatic selection of an optimal number of clusters included 100% of cases, generating an initial 6-cluster solution and a final 4-cluster solution. The interpretation of within-group ranking of the importance of variables in the clustering solutions resulted in the following characterization of clusters: chronic facial pain (n = 36, acute muscle pain (n = 125, acute articular pain (n = 75 and chronic articular impairment (n = 121. Conclusion Subgroups of acute and chronic TMD patients seeking treatment can be identified using clustering methods to provide a better understanding of the clinical presentation of TMD when multiple diagnosis are present. Classifying patients into identifiable symptomatic profiles would help clinicians to estimate how common a disorder is within a population of

  3. A clinical profile of compulsive exercise in adolescent inpatients with anorexia nervosa

    OpenAIRE

    Noetel, Melissa; Miskovic-Wheatley, Jane; Crosby, Ross D.; Hay, Phillipa; Madden, Sloane; Touyz, Stephen

    2016-01-01

    Background The aim of the current study was to contribute to the development of a clinical profile of compulsive exercise in adolescents with Anorexia Nervosa (AN), by examining associations between compulsive exercise and eating and general psychopathology. Method A sample of 60 female adolescent inpatients with AN completed a self-report measure of compulsive exercise and a series of standardized self-report questionnaires assessing eating and general psychopathology. Results Higher levels ...

  4. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

    OpenAIRE

    Alberto Tobón-Castaño; Esteban Mesa-Echeverry; Andrés Felipe Miranda-Arboleda

    2015-01-01

    Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the cl...

  5. THE STUDY OF PREVALENCE AND CLINICAL PROFILE OF VALVULAR HEART DISEASES IN A TEACHING HOSPITAL

    OpenAIRE

    Radha Krishnan; Srinivas

    2015-01-01

    Valvular heart disease is still a common causes of mortality and morbidity in India and rheumatic heart disease is still far more frequent. AIMS AND OBJECTIVES: To study the prevalence and clinical profile of rheumatic and non - rheumatic valvular heart dise ase in patients attending to Government General Hospital, Kakinada. MATERIALS AND METHODS: 100 Adult patients with valvular abnormalities attending to the Medicine and Cardiol...

  6. Dengue infection in children and adolescents: Clinical profile in a reference hospital in northeast Brazil

    Directory of Open Access Journals (Sweden)

    Roberto da Justa Pires Neto

    2013-12-01

    Full Text Available Introduction This study aimed to describe the clinical spectrum of dengue in children and adolescents from a hyperendemic region who were admitted for hospitalization. Methods A retrospective study was conducted on patients diagnosed with dengue infection upon admission to a reference center in Fortaleza, Brazil. Results Of the 84 patients included, 42 underwent confirmatory testing. The main symptoms were fever, abdominal pain and vomiting. The median level of serum aspartate aminotransferase was 143.5±128mg/dL. Conclusions A peculiar clinical profile was evident among children and adolescents with dengue infection in a reference center in northeast Brazil, including gastrointestinal symptoms and liver involvement.

  7. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study.

    Science.gov (United States)

    Schwalbe, Edward C; Lindsey, Janet C; Nakjang, Sirintra; Crosier, Stephen; Smith, Amanda J; Hicks, Debbie; Rafiee, Gholamreza; Hill, Rebecca M; Iliasova, Alice; Stone, Thomas; Pizer, Barry; Michalski, Antony; Joshi, Abhijit; Wharton, Stephen B; Jacques, Thomas S; Bailey, Simon; Williamson, Daniel; Clifford, Steven C

    2017-07-01

    International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0-16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3-16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MBWNT remained unchanged and each remaining consensus subgroup was split in two. MBSHH was split into age-dependent subgroups corresponding to infant (<4·3 years; MBSHH-Infant; n=65) and

  8. Advances and Challenges in Liquid Chromatography-Mass Spectrometry-Based Proteomics Profiling for Clinical Applications

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Weijun; Jacobs, Jon M.; Liu, Tao; Camp, David G.; Smith, Richard D.

    2006-08-01

    The advances in proteomic technologies provide tremendous opportunities for applying these technologies in biomarker-related clinical applications; however, the unique characteristics of human biofluids such as high dynamic range in protein abundances and extreme complexity of human proteomes present tremendous challenges for current analytical technologies. In this review, we focus on summarizing the recent advances in LC-MS based proteomic profiling and its applications in clinical proteomics as well as the major challenges for implementing these technologies for more effective biomarker discovery. Over the last few years, tremendous efforts have been directed towards the development of more effective approaches for characterizing the human plasma/serum and other biofluid proteomes. The developments in immunodepletion and various fractionation approaches in combination with much improved LC-MS platforms have enabled the profiling of the plasma proteome with much greater dynamic range of coverage, allowing many proteins at low ng/mL levels being confidently identified. Despite the significant advances and efforts, the dynamic range of measurements or extent of proteome coverage, the confidence of peptide/protein identification, the accuracy of quantitation, the throughput of analysis, and the robustness of the present instrumentation are still among the major challenges for implementation of a proteomic profiling platform suitable for efficient clinical applications.

  9. Developing a clinical model to predict the need for relaparotomy in ...

    African Journals Online (AJOL)

    This model had a predictive value of >90%. Conclusions. We have constructed a model that uses clinical data available at initial laparotomy to predict the need for subsequent relaparotomy in patients with complicated acute appendicitis. It is hoped that this model can be integrated into routine clinical practice, but further ...

  10. The use of clinical profiles in the investigation of foodborne outbreaks in restaurants: United States, 1982-1997.

    Science.gov (United States)

    Hedberg, C W; Palazzi-Churas, K L; Radke, V J; Selman, C A; Tauxe, R V

    2008-01-01

    Improving the efficiency of outbreak investigation in restaurants is critical to reducing outbreak-associated illness and improving prevention strategies. Because clinical characteristics of outbreaks are usually available before results of laboratory testing, we examined their use for determining contributing factors in outbreaks caused by restaurants. All confirmed foodborne outbreaks reported to the Centers for Disease Control and Prevention (CDC) from 1982 to 1997 were reviewed. Clinical profiles were developed based on outbreak characteristics. We compared the percentage of contributing factors by known agent and clinical profile to their occurrence in outbreaks of unclassified aetiology. In total, 2246 foodborne outbreaks were included: 697 (31%) with known aetiology and 1549 (69%) with aetiology undetermined. Salmonella accounted for 65% of outbreaks with a known aetiology. Norovirus-like clinical profiles were noted in 54% of outbreaks with undetermined aetiology. Improper holding times and temperatures were associated with outbreaks caused by Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, and Salmonella, and also with outbreaks of undetermined aetiology that fitted diarrhoea-toxin and vomiting-toxin clinical profiles. Poor personal hygiene was associated with norovirus, Shigella, and Salmonella, and also with outbreaks that fitted norovirus-like and vomiting-toxin clinical profiles. Contributing factors were similar for outbreaks with known aetiology and for those where aetiology was assigned by corresponding clinical profile. Rapidly categorizing outbreaks by clinical profile, before results of laboratory testing are available, can help identification of factors which contributed to the occurrence of the outbreak and will promote timely and efficient outbreak investigations.

  11. Predicting lesion size during focused ultrasound thalamotomy: a review of 63 lesions over 3 clinical trials.

    Science.gov (United States)

    Bond, Aaron E; Elias, W Jeffrey

    2018-02-01

    OBJECTIVE The goal of this study was to improve the predictability of lesion size during focused ultrasound (FUS) thalamotomy procedures. METHODS Treatment profiles and T2-weighted MRI (T2 MRI) studies obtained in 63 patients who participated in 3 clinical trials of FUS thalamotomy from February 2011 to March 2015 were reviewed retrospectively. Four damage estimate models were compared with lesion sizes measured on postprocedural T2 MRI. Models were based on 54°C × 3 seconds, 240 cumulative equivalent minutes at 43°C, and simple thermal threshold analysis, which recorded the maximum diameter that reached a temperature of at least 51°C and 54°C. Energy requirements per °C thermal rise above 37°C were also recorded. RESULTS Lesion diameters from T2 MRI correlated poorly from the day of the procedure to day 1 postprocedure (mean increase 78% [SD 79%]). There was more predictability of lesion size from day 1 to day 30, with a mean reduction in lesion diameter of 11% (SD 24%). Of the 4 models tested, the most correlative model to day 1 findings on T2 MRI was a 51°C threshold. The authors observed an increase in the energy requirement for each subsequent treatment sonication, with the largest percentage increase from treatment sonication 1 to treatment sonication 2 (mean increase 20% in energy required per °C increase in temperature above 37°C). CONCLUSIONS At the margins, 51°C temperature threshold diameters correlated best to lesion diameters measured at day 1 with T2 MRI. The lesion size from T2 MRI decreases from day 1 to day 30 in a predictable manner, much more so than from the day of the procedure to day 1 postprocedure. Energy requirements per °C rise above 37°C continuously increase with each successive sonication.

  12. Comatose and noncomatose adult diabetic ketoacidosis patients at the University Teaching Hospital, Zambia: Clinical profiles, risk factors, and mortality outcomes

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    Mwanja Kakusa

    2016-01-01

    Full Text Available Background: Diabetic ketoacidosis (DKA is one of the commonly encountered diabetes mellitus emergencies. Aim: This study aimed at describing the clinical profiles and hospitalization outcomes of DKA patients at the University Teaching Hospital (UTH in Lusaka, Zambia and to investigate the role of coma on mortality outcome. Materials and Methods: This was a cross-sectional analytical study of hospitalized DKA patients at UTH. The data collected included clinical presentation, precipitating factors, laboratory profiles, complications, and hospitalization outcomes. Primary outcome measured was all-cause in-hospital mortality. Results: The median age was 40 years. Treatment noncompliance was the single highest identified risk factor for development of DKA, followed by new detection of diabetes, then infections. Comatose patients were significantly younger, had lower baseline blood pressure readings, and higher baseline respiratory rates compared to noncomatose patients. In addition, comatose patients had higher baseline admission random blood glucose readings. Their baseline sodium and chloride levels were also higher. The prevalences of hypokalemia, hypernatremia, and hyperchloremia were also higher among comatose patients compared to noncomatose patients. Development of aspiration during admission with DKA, pneumonia at baseline, development of renal failure, and altered mental status were associated with an increased risk of mortality. Development of renal failure was independently predictive of mortality. Conclusion: The mortality rate from DKA hospitalizations is high at UTH. Treatment noncompliance is the single highest identifiable precipitant of DKA. Aspiration, development of renal failure, altered sensorium, and pneumonia at baseline are associated with an increased risk of mortality. Development of renal failure during admission is predictive of mortality.

  13. Predictive value of clinical history compared with urodynamic study in 1,179 women

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    Jorge Milhem Haddad

    2016-02-01

    Full Text Available SUMMARY Objective: to determine the positive predictive value of clinical history in comparison with urodynamic study for the diagnosis of urinary incontinence. Methods: retrospective analysis comparing clinical history and urodynamic evaluation of 1,179 women with urinary incontinence. The urodynamic study was considered the gold standard, whereas the clinical history was the new test to be assessed. This was established after analyzing each method as the gold standard through the difference between their positive predictive values. Results: the positive predictive values of clinical history compared with urodynamic study for diagnosis of stress urinary incontinence, overactive bladder and mixed urinary incontinence were, respectively, 37% (95% CI 31-44, 40% (95% CI 33-47 and 16% (95% CI 14-19. Conclusion: we concluded that the positive predictive value of clinical history was low compared with urodynamic study for urinary incontinence diagnosis. The positive predictive value was low even among women with pure stress urinary incontinence.

  14. IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples.

    Science.gov (United States)

    Hintzsche, Jennifer; Kim, Jihye; Yadav, Vinod; Amato, Carol; Robinson, Steven E; Seelenfreund, Eric; Shellman, Yiqun; Wisell, Joshua; Applegate, Allison; McCarter, Martin; Box, Neil; Tentler, John; De, Subhajyoti; Robinson, William A; Tan, Aik Choon

    2016-07-01

    Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine.IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT. © The Author 2016. Published by Oxford University Press on behalf of the American Medical

  15. CLINICAL PROFILE OF ACUTE LOWER RESPIRATORY TRACT INFECTIONS IN CHILDREN BETWEEN 2MONTHS TO 5 YEARS

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    Amitoj Singh Chhina

    2015-08-01

    Full Text Available BACKGROUND : Acute respiratory infections are a leading cause of morbidity and mortality in under - five children in developing countries. Hence, the present study was undertaken to study the various risk factors, clinical profile and outcome of acute lower respiratory tract infections (ALRI in children aged 2 month to 5 years. OBJECTIVE : clinical features, laborato ry assessment and morbidity and mortality pattern associated with acute lower respiratory tract infections in children aged 2 months to 5 years. METHODS: 100 ALRI cases fulfilling WHO criteria for pneumonia, in the age group of 2 month to 5 years were evaluated for clinical profile as per a predesigned proforma in a rural medical college. RESULTS : Of cases 61% were infants and remaining 39%12 - 60 months age group, males outnumbered females with sex ratio of 1.3;1. Elevated total leukocyte counts for age were observed in only 22% of cases, of these 3% were having pneumonia, 9% severe pneumonia and 10% very severe pneumonia. Significant association was found between leukocytosis and ALRI severity (p= 0.0001 Positive blood culture was obtained in 8% of cases and was significantly associated with ALRI severity (p=. 0.027. Among the ALRI cases, 84% required oxygen supplementation at any time during the hospital stay and 8% required mechanical ventilation. The mortality rate was 1%; with 99% of cases recovering and getting discharged uneventfully. CONCLUSION : Among the clinical variables, the signs and symptoms of ALRI as per the WHO ARI Control Programme were found in almost all cases. Regarding the laboratory profile, leukocytosis and blood culture positivity w ere observed in a small percentage, but significant association with ALRI severity was observed for both. Thus, clinical signs, and not invasive blood tests are a better diagnostic tools, though the latter may provide additional therapeutic and prognostic information in severe disease

  16. Comparison of statistical and clinical predictions of functional outcome after ischemic stroke.

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    Douglas D Thompson

    Full Text Available To determine whether the predictions of functional outcome after ischemic stroke made at the bedside using a doctor's clinical experience were more or less accurate than the predictions made by clinical prediction models (CPMs.A prospective cohort study of nine hundred and thirty one ischemic stroke patients recruited consecutively at the outpatient, inpatient and emergency departments of the Western General Hospital, Edinburgh between 2002 and 2005. Doctors made informal predictions of six month functional outcome on the Oxford Handicap Scale (OHS. Patients were followed up at six months with a validated postal questionnaire. For each patient we calculated the absolute predicted risk of death or dependence (OHS≥3 using five previously described CPMs. The specificity of a doctor's informal predictions of OHS≥3 at six months was good 0.96 (95% CI: 0.94 to 0.97 and similar to CPMs (range 0.94 to 0.96; however the sensitivity of both informal clinical predictions 0.44 (95% CI: 0.39 to 0.49 and clinical prediction models (range 0.38 to 0.45 was poor. The prediction of the level of disability after stroke was similar for informal clinical predictions (ordinal c-statistic 0.74 with 95% CI 0.72 to 0.76 and CPMs (range 0.69 to 0.75. No patient or clinician characteristic affected the accuracy of informal predictions, though predictions were more accurate in outpatients.CPMs are at least as good as informal clinical predictions in discriminating between good and bad functional outcome after ischemic stroke. The place of these models in clinical practice has yet to be determined.

  17. Prediction of euphotic depths and diffuse attenuation coefficients from absorption profiles: a model based on comparisons between vertical profiles of spectral absorption, spectral irradiance, and P

    Science.gov (United States)

    Zaneveld, J. Ronald V.; Pegau, Scott; Barnard, Andrew H.; Mueller, James L.; Maske, Helmut; Valdez, Eduardo; Lara-Lara, Ruben; Alvarez-Borrego, Saul

    1997-02-01

    A model is presented which predicts the diffuse attenuation coefficient of downwelling irradiance as a function of depth and the depth of the euphotic zone as based on the one percent level of photosynthetically active radiation from vertical profiles of spectral absorption and attenuation. The model is tested using data obtained in the Gulf of California. The modeled diffuse attenuation coefficients and PAR levels ar shown to have average errors of less than five percent when compared to the measured values.

  18. Profile of the Pleximmune blood test for transplant rejection risk prediction

    Science.gov (United States)

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Levy, Samantha; Soltys, Kyle; Bond, Geoffrey; Mazariegos, George; Ranganathan, Sarangarajan; Zeevi, Adriana

    2016-01-01

    Summary The Pleximmune™ test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein–Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 81% respectively in training set–validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require an accurate management of cellular immune responses in clinical practice. PMID:26760313

  19. predicted peak expiratory flow in human and the clinical implication ...

    African Journals Online (AJOL)

    DR. AMINU

    classification of severe (47%) using one, but moderate (71%) using another. This indicates that predicted PEF varied widely across formulae and choice of a particular formula may alter guideline- base care. This work has therefore accepted a recently published population-base equation proposed as the reference standard ...

  20. Clinical profile of high-risk febrile neutropenia in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Mohan V Bhojaraja

    2016-06-01

    Full Text Available Background Infection in the immunocompromised host has been a reason of concern in the clinical setting and a topic of debate for decades. In this study, the aim was to analyse the clinical profile of high-risk febrile neutropenic patients. Aims To study the clinical profile of high risk febrile neutropenia patients with the objective of identifying the most common associated malignancy, most common associated pathogen, the source of infection, to correlate the treatment and management with that of the Infectious Diseases Society of America (IDSA 2010 guidelines and to assess the clinical outcome. Methods A cross-sectional time bound study was carried out and a total of 80 episodes of high-risk febrile neutropenia were recorded among patients with malignancies from September 2011 to July 2013 with each episode being taken as a new case. Results Non-Hodgkin’s lymphoma (30 per cent was the most common malignancy associated, commonest source of infection was due to central venous catheters, the commonest pathogens were gram negative (52 per cent the treatment and management of each episode of high risk febrile neutropenia correlated with that of IDSA 2010 guidelines and the mortality rate was 13.75 per cent. Conclusion Febrile neutropenia is one of the major complications and cause of mortality in patients with malignancy and hence understanding its entire spectrum can help us reduce morbidity and mortality.

  1. Multiple sclerosis: clinical profiling and data collection as prerequisite for personalized medicine approach.

    Science.gov (United States)

    Ziemssen, Tjalf; Kern, Raimar; Thomas, Katja

    2016-08-02

    Multiple sclerosis (MS) is a highly heterogeneous disease as it can present inter-individually as well as intra-individually, with different disease phenotypes emerging during different stages in the long-term disease course. In addition to advanced immunological, genetic and magnetic resonance imaging (MRI) profiling of the patient, the clinical profiling of MS patients needs to be widely implemented in clinical practice and improved by including a greater range of relevant parameters as patient-reported outcomes. It is crucial to implement a high standard of clinical characterization of individual patients as this is key to effective long-term observation and evaluation.To generate reliable real-world data, individual clinical data should be collected in specific MS registries and/or using intelligent software instruments as the Multiple Sclerosis Documentation System 3D. Computational analysis of biological processes will play a key role in the transition to personalized MS treatment. Major breakthroughs in the areas of bioinformatics and computational systems biology will be required to process this complex information to enable improved personalization of treatment for MS patients.

  2. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Rajesh Joshi

    2015-01-01

    Full Text Available Objective: To determine the prevalence of celiac disease (CD in children with type 1 diabetes mellitus (TIDM in follow-up in a Tertiary Care Referral Centre in Western India and to describe the clinical features indicative of CD in screened patients of TIDM. Study Design: In this single center observational cross-sectional study, 71 children who were diagnosed with TIDM were subjected to screening for CD with tissue transglutaminase antibody testing. Those who tested positive were offered intestinal biopsy for the confirmation of diagnosis. Clinical profiles of both groups of patients were compared and manifestations of CD were delineated. Results: The study revealed the prevalence of CD (based on serology in children with Type 1 diabetes as 15.49%. The prevalence of biopsy-confirmed CD was 7.04%. Of the diagnosed CD patients, one-third were symptomatic at the time of screening while the majority was asymptomatic. The major clinical features indicative of CD were intestinal symptoms, anemia, rickets, and short stature. Autoimmune thyroid disease was prevalent in 29.6% of the patients with TIDM followed by CD. Conclusions: The high prevalence of CD in children with Type 1 diabetes emphasizes the need for routine screening programs to be in place for these high-risk populations. The clinical profile of patients with CD further elaborates the indicators of CD and the need to screen for them.

  3. Clinical and epidemiological profile of patients with valvular heart disease admitted to the emergency department

    Energy Technology Data Exchange (ETDEWEB)

    Moraes, Ricardo Casalino Sanches de [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Katz, Marcelo [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Tarasoutchi, Flávio [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    To evaluate the clinical and epidemiological profile of patients with valvular heart disease who arrived decompensated at the emergency department of a university hospital in Brazil. A descriptive analysis of clinical and echocardiographic data of 174 patients with severe valvular disease, who were clinically decompensated and went to the emergency department of a tertiary cardiology hospital, in the State of São Paulo, in 2009. The mean age of participants was 56±17 years and 54% were female. The main cause of valve disease was rheumatic in 60%, followed by 15% of degenerative aortic disease and mitral valve prolapse in 13%. Mitral regurgitation (27.5%) was the most common isolated valve disease, followed by aortic stenosis (23%), aortic regurgitation (13%) and mitral stenosis (11%). In echocardiographic data, the mean left atrial diameter was 48±12mm, 38±12mm for the left ventricular systolic diameter, and 54±12mm for the diastolic diameter; the mean ejection fraction was 56±13%, and the mean pulmonary artery pressure was 53±16mmHg. Approximately half of patients (44%) presented atrial fibrillation, and over one third of them (37%) had already undergone another cardiac surgery. Despite increased comorbidities and age-dependent risk factors commonly described in patients with valvular heart disease, the clinical profile of patients arriving at the emergency department represented a cohort of rheumatic patients in more advanced stages of disease. These patients require priority care in high complexity specialized hospitals.

  4. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  5. Pattern of Altered Lipid Profile in Patients with Subclinical and Clinical Hypothyroidism and its Correlation with Body Mass Index.

    Science.gov (United States)

    Humerah, Sobia; Siddiqui, Arif; Khan, Humaira Fayyaz

    2016-06-01

    To compare the lipid profile of the subclinical and clinical hypothyroid patients and to evaluate the correlation between body mass index (BMI) and lipid profile in hypothyroidism. Cross-sectional study. Islamic International Medical College, Riphah International University, Islamabad, and Citi Laboratory, Rawalpindi, from January to December 2013. The subjects were selected through non-probability, purposive sampling. On the basis of thyroid profile, the subjects were divided into 3 groups: euthyroids (n=20), subclinical hypothyroids (n=50), and clinical hypothyroids (n=30). The blood of these subjects was then analyzed for lipid profile. Data was analyzed using SPSS version 18 statistical software. Both hypothyroid groups showed altered lipid profile which was observed to be significantly raised when compared with the euthyroid subjects. Comparison of lipid profile in euthyroid, subclinical, and clinical hypothyroid groups showed significant differences by non-parametric tests (p Hypothyroidism causes alteration of lipid profile. Clinical and subclinical hypothyroid patients have altered lipid profile as compared to euthyroids. Thyroid status monitoring is very important, since it can induce changes in lipid profile. Such dyslipidemic status is significant not only for the management of thyroid disorders but also for common diseases like obesity and coronary atherosclerosis in the population.

  6. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed trials.

    Directory of Open Access Journals (Sweden)

    Melissa Paoloni

    Full Text Available BACKGROUND: Molecularly-guided trials (i.e. PMed now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. METHODOLOGY: A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77% successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days. Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. CONCLUSIONS: Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week. Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of

  7. Prostate cancer risk prediction in a urology clinic in Mexico

    Science.gov (United States)

    Liang, Yuanyuan; Messer, Jamie C; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

    2012-01-01

    Objectives To evaluate factors affecting the risk of prostate cancer (PCa) and high-grade disease (HGPCa, Gleason score ≥7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). Methods and Materials From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of PCa, and history of a prior prostate biopsy on PCa and HGPCa separately. Internal discrimination, goodness-of-fit and clinical utility of the resulting models were assessed with comparison to the PCPTRC. Results Rates of both PCa (73.2%) and HGPCa (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of PCa but overestimated the risk of HGPCa. Four factors influencing PCa on biopsy were logPSA, DRE, family history and a prior biopsy history (all purological checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics. PMID:22306115

  8. Clinical and demographical profile of inpatient psychiatry referrals in a multispecialty teaching hospital

    Directory of Open Access Journals (Sweden)

    Vijay Niranjan

    2017-06-01

    Full Text Available Background: Research in consultation-liaison psychiatry is important clinically because of high incidence of coexistence of psychiatric and medical disorders in patients attending psychiatry and general healthcare systems. In contrast to west, research about liaison psychiatry in India has been minimal. Thus a study about understanding clinical and sociodemographic profile patterns of inpatient psychiatry referrals was undertaken to enhance our knowledge of this field. Objective: To describe the clinical and socio-demographic profile of inpatient psychiatry referrals in a multispecialty teaching hospital. Materials and methods: The study population comprised all consecutive inpatients who were referred for psychiatric consultation from other departments of a multispecialty teaching hospital over a period of six months. In a semi-structured proforma, socio-demographic profile of patients, referring departments, reason of referral, psychiatric diagnosis, and physical illness diagnosis were recorded and analysed using descriptive statistics. Results: A total of 356 patients were referred for psychiatric consultation, 55.9% were males and 44.1% were females. Majority of patients belonged to 20-40 years age group (37.9%. Department of medicine made majority of the psychiatric referrals (50.6%; commonest reason for referral was abnormal behaviour (30.9%, followed by suicidal/self-harm acts (17.9%, and past psychiatric history (10.9%. The most commonly diagnosed psychiatric disorders were delirium (17.9%, followed by organic psychosis/mood disorder (14.8%, substance related disorder (12.9%, and depression (12.9%. Conclusion: There is an urgent need for raising awareness among all physicians and medical staff regarding early recognition and prompt referral for psychiatric problems. Also further research is warranted, especially longitudinal studies with outcome variables and various clinical processes related to consultation-liaison psychiatry.

  9. Pressure Ulcers in Adults: Prediction and Prevention. Clinical Practice Guideline Number 3.

    Science.gov (United States)

    Agency for Health Care Policy and Research (DHHS/PHS), Rockville, MD.

    This package includes a clinical practice guideline, quick reference guide for clinicians, and patient's guide to predicting and preventing pressure ulcers in adults. The clinical practice guideline includes the following: overview of the incidence and prevalence of pressure ulcers; clinical practice guideline (introduction, risk assessment tools…

  10. Prediction of renal mass aggressiveness using clinical and radiographic features: a global, multicentre prospective study

    NARCIS (Netherlands)

    Golan, Shay; Eggener, Scott; Subotic, Svetozar; Barret, Eric; Cormio, Luigi; Naito, Seiji; Tefekli, Ahmet; Pilar Laguna Pes, M.

    2016-01-01

    To examine the ability of preoperative clinical characteristics to predict histological features of renal masses (RMs). Data from consecutive patients with clinical stage I RMs treated surgically between 2010 and 2011 in the Clinical Research Office of Endourology Society (CROES) Renal Mass Registry

  11. Predicting miRNA Targets by Integrating Gene Regulatory Knowledge with Expression Profiles.

    Directory of Open Access Journals (Sweden)

    Weijia Zhang

    Full Text Available microRNAs (miRNAs play crucial roles in post-transcriptional gene regulation of both plants and mammals, and dysfunctions of miRNAs are often associated with tumorigenesis and development through the effects on their target messenger RNAs (mRNAs. Identifying miRNA functions is critical for understanding cancer mechanisms and determining the efficacy of drugs. Computational methods analyzing high-throughput data offer great assistance in understanding the diverse and complex relationships between miRNAs and mRNAs. However, most of the existing methods do not fully utilise the available knowledge in biology to reduce the uncertainty in the modeling process. Therefore it is desirable to develop a method that can seamlessly integrate existing biological knowledge and high-throughput data into the process of discovering miRNA regulation mechanisms.In this article we present an integrative framework, CIDER (Causal miRNA target Discovery with Expression profile and Regulatory knowledge, to predict miRNA targets. CIDER is able to utilise a variety of gene regulation knowledge, including transcriptional and post-transcriptional knowledge, and to exploit gene expression data for the discovery of miRNA-mRNA regulatory relationships. The benefits of our framework is demonstrated by both simulation study and the analysis of the epithelial-to-mesenchymal transition (EMT and the breast cancer (BRCA datasets. Our results reveal that even a limited amount of either Transcription Factor (TF-miRNA or miRNA-mRNA regulatory knowledge improves the performance of miRNA target prediction, and the combination of the two types of knowledge enhances the improvement further. Another useful property of the framework is that its performance increases monotonically with the increase of regulatory knowledge.

  12. Ruptured corpus luteal cyst: Prediction of clinical outcomes with CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Seok; Moon, Min Hoan; Woo, Hyun Sik; Sung, Chang Kyu; Jeon, Hye Won; Lee, Taek Sang [SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2017-08-01

    To evaluate the determinant pretreatment CT findings that can predict surgical intervention for patients suffering from corpus luteal cyst rupture with hemoperitoneum. From January 2009 to December 2014, a total of 106 female patients (mean age, 26.1 years; range, 17–44 years) who visited the emergency room of our institute for acute abdominal pain and were subsequently diagnosed with ruptured corpus luteal cyst with hemoperitoneum were included in the retrospective study. The analysis of CT findings included cyst size, cyst shape, sentinel clot sign, ring of fire sign, hemoperitoneum depth, active bleeding in portal phase and attenuation of hemoperitoneum. The comparison of CT findings between the surgery and conservative management groups was performed with the Mann-Whitney U test or chi-square test. Logistic regression analysis was used to determine significant CT findings in predicting surgical intervention for a ruptured cyst. Comparative analysis revealed that the presence of active bleeding and the hemoperitoneum depth were significantly different between the surgery and conservative management groups and were confirmed as significant CT findings for predicting surgery, with adjusted odds ratio (ORs) of 3.773 and 1.318, respectively (p < 0.01). On the receiver-operating characteristic curve analysis for hemoperitoneum depth, the optimal cut-off value was 5.8 cm with 73.7% sensitivity and 58.6% specificity (Az = 0.711, p = 0.004). In cases with a hemoperitoneum depth > 5.8 cm and concurrent active bleeding, the OR for surgery increased to 5.786. The presence of active bleeding and the hemoperitoneum depth on a pretreatment CT scan can be predictive warning signs of surgery for a patient with a ruptured corpus luteal cyst with hemoperitoneum.

  13. Exploring the clinical validity of predicted TRE in navigation

    Science.gov (United States)

    Bickel, M.; Güler, Ö.; Kral, F.; Schwarm, F.; Freysinger, W.

    2010-02-01

    In a detailed laboratory investigation we performed a series of experiments in order to assess the validity of the widely used TRE concept to predict the application accuracy. On base of 1mm CT scan a plastic skull, a cadaver head and a volunteer were registered to an in house navigation system. We stored the position data of an optical camera (NDI Polaris) for registration with pre-defined CT coordinates. For every specimen we choose 3, 5, 7 and 9 registration and 10 evaluation points, respectively, performing 10 registrations. The data were evaluated both with the Arun and the Horn approaches. The vectorial difference between actual and predefined position in the CT data set was stored and evaluated for FRE and TRE. Evaluation and visualization was implemented in Matlab. The data were analyzed, specifically for normal distribution, with MS Excel and SPSS Version 15.0. For the plastic skull and the anatomic specimen submillimetric application accuracy was found experimentally and confirmed by the calculated TRE. Since for the volunteer no Titanium screws were implanted anatomic landmarks had to be used for registration and evaluation; an application accuracy in the low millimeter regime was found in all approaches. However, the detailed statistical analysis of the data revealed that the model predictions and the actual measurements do not exhibit a strong statistical correlation (p data suggest that the TRE predictions are too optimistic and should be used with caution intraoperatively.

  14. Predicting clinical image delivery time by monitoring PACS queue behavior.

    Science.gov (United States)

    King, Nelson E; Documet, Jorge; Liu, Brent

    2006-01-01

    The expectation of rapid image retrieval from PACS users contributes to increased information technology (IT) infrastructure investments to increase performance as well as continuing demands upon PACS administrators to respond to "slow" system performance. The ability to provide predicted delivery times to a PACS user may curb user expectations for "fastest" response especially during peak hours. This, in turn, could result in a PACS infrastructure tailored to more realistic performance demands. A PACS with a stand-alone architecture under peak load typically holds study requests in a queue until the DICOM C-Move command can take place. We investigate the contents of a stand-alone architecture PACS RetrieveSend queue and identified parameters and behaviors that enable a more accurate prediction of delivery time. A prediction algorithm for studies delayed in a stand-alone PACS queue can be extendible to other potential bottlenecks such as long-term storage archives. Implications of a queue monitor in other PACS architectures are also discussed.

  15. Soil profile organic carbon prediction with Visible Near Infrared Reflec-tance spectroscopy based on a national database

    DEFF Research Database (Denmark)

    Deng, Fan; Knadel, Maria; Peng, Yi

    This study focuses on the application of the Danish national soil Visible Near Infrared Re-flectance spectroscopy (NIRs) database for predicting SOC in a field. The Conditioned Latin hypercube sam-pling (cLHS) method was used for the selection of 120 soil profiles based on DualEM21s and DEM data...

  16. DIGEP-Pred: web service for in silico prediction of drug-induced gene expression profiles based on structural formula.

    Science.gov (United States)

    Lagunin, Alexey; Ivanov, Sergey; Rudik, Anastasia; Filimonov, Dmitry; Poroikov, Vladimir

    2013-08-15

    Experimentally found gene expression profiles are used to solve different problems in pharmaceutical studies, such as drug repositioning, resistance, toxicity and drug-drug interactions. A special web service, DIGEP-Pred, for prediction of drug-induced changes of gene expression profiles based on structural formulae of chemicals has been developed. Structure-activity relationships for prediction of drug-induced gene expression profiles were determined by Prediction of Activity Spectra for Substances (PASS) software. Comparative Toxicogenomics Database with data on the known drug-induced gene expression profiles of chemicals was used to create mRNA- and protein-based training sets. An average prediction accuracy for the training sets (ROC AUC) calculated by leave-one-out cross-validation on the basis of mRNA data (1385 compounds, 952 genes, 500 up- and 475 down-regulations) and protein data (1451 compounds, 139 genes, 93 up- and 55 down-regulations) exceeded 0.85. Freely available on the web at http://www.way2drug.com/GE.

  17. The Impact of Mission Profile Models on the Predicted Lifetime of IGBT Modules in the Modular Multilevel Converter

    DEFF Research Database (Denmark)

    Zhang, Yi; Wang, Huai; Wang, Zhongxu

    2017-01-01

    The reliability aspect study of Modular Multilevel Converter (MMC) is of great interest in industry applications, such as offshore wind. Lifetime prediction of key components is an important tool to design MMC with fulfilled reliability specifications. While many efforts have been made...... and electrical power modeling methods on the estimated lifetime of IGBT modules in an MMC for offshore wind power application. In a 30 MW MMC case study, an annual wind speed profile with a resolution of 1 s/data, 10 minute/data, and 1 hour/data are considered, respectively. A method to re-generate higher...... used in the MMC, resulting in significant differences. The study serves as a first step to quantify the impact of mission profile modeling on lifetime prediction, and to provide a guideline on mission profile collection for the presented application....

  18. Somatic cell count distributions during lactation predict clinical mastitis

    NARCIS (Netherlands)

    Green, M.J.; Green, L.E.; Schukken, Y.H.; Bradley, A.J.; Peeler, E.J.; Barkema, H.W.; Haas, de Y.; Collis, V.J.; Medley, G.F.

    2004-01-01

    This research investigated somatic cell count (SCC) records during lactation, with the purpose of identifying distribution characteristics (mean and measures of variation) that were most closely associated with clinical mastitis. Three separate data sets were used, one containing quarter SCC (n =

  19. Clinical Findings and Genetic Expression Profiling of Three Pigmented Lesions of the Optic Nerve

    Directory of Open Access Journals (Sweden)

    Manuel A. de Alba

    2015-01-01

    Full Text Available Background. Optic disk melanocytoma is a primary tumor of the optic disk that represents a clinical diagnostic challenge due to its similarities with melanoma. Purpose. The authors present three cases in which genetic expression profiling was used to identify tumor prognosis of optic disk melanocytoma. Case Series. In two cases fine-needle aspiration biopsy was performed to obtain tissue through a transvitreal route into the apex of the tumor while the patient underwent pars plana vitrectomy, laser ablation, phacoemulsification with posterior chamber intraocular lens implantation, and intravitreal triamcinolone acetonide. In the other case the tissue was obtained after definite enucleation. Conclusion. Genetic expression profiling is a useful diagnostic tool for classification and can provide vital information to the ocular oncologist regarding prognosis.

  20. Metabolite Profile of Cervicovaginal Fluids from Early Pregnancy Is Not Predictive of Spontaneous Preterm Birth

    Directory of Open Access Journals (Sweden)

    Melinda M. Thomas

    2015-11-01

    Full Text Available In our study, we used a mass spectrometry-based metabolomic approach to search for biomarkers that may act as early indicators of spontaneous preterm birth (sPTB. Samples were selected as a nested case-control study from the Screening for Pregnancy Endpoints (SCOPE biobank in Auckland, New Zealand. Cervicovaginal swabs were collected at 20 weeks from women who were originally assessed as being at low risk of sPTB. Samples were analysed using gas chromatography-mass spectrometry (GC-MS. Despite the low amount of biomass (16–23 mg, 112 compounds were detected. Statistical analysis showed no significant correlations with sPTB. Comparison of reported infection and plasma inflammatory markers from early pregnancy showed two inflammatory markers were correlated with reported infection, but no correlation with any compounds in the metabolite profile was observed. We hypothesise that the lack of biomarkers of sPTB in the cervicovaginal fluid metabolome is simply because it lacks such markers in early pregnancy. We propose alternative biofluids be investigated for markers of sPTB. Our results lead us to call for greater scrutiny of previously published metabolomic data relating to biomarkers of sPTB in cervicovaginal fluids, as the use of small, high risk, or late pregnancy cohorts may identify metabolite biomarkers that are irrelevant for predicting risk in normal populations.

  1. Prediction of incidence and stability of alcohol use disorders by latent internalizing psychopathology risk profiles in adolescence and young adulthood.

    Science.gov (United States)

    Behrendt, Silke; Bühringer, Gerhard; Höfler, Michael; Lieb, Roselind; Beesdo-Baum, Katja

    2017-10-01

    Comorbid internalizing mental disorders in alcohol use disorders (AUD) can be understood as putative independent risk factors for AUD or as expressions of underlying shared psychopathology vulnerabilities. However, it remains unclear whether: 1) specific latent internalizing psychopathology risk-profiles predict AUD-incidence and 2) specific latent internalizing comorbidity-profiles in AUD predict AUD-stability. To investigate baseline latent internalizing psychopathology risk profiles as predictors of subsequent AUD-incidence and -stability in adolescents and young adults. Data from the prospective-longitudinal EDSP study (baseline age 14-24 years) were used. The study-design included up to three follow-up assessments in up to ten years. DSM-IV mental disorders were assessed with the DIA-X/M-CIDI. To investigate risk-profiles and their associations with AUD-outcomes, latent class analysis with auxiliary outcome variables was applied. AUD-incidence: a 4-class model (N=1683) was identified (classes: normative-male [45.9%], normative-female [44.2%], internalizing [5.3%], nicotine dependence [4.5%]). Compared to the normative-female class, all other classes were associated with a higher risk of subsequent incident alcohol dependence (pdisorder (SUD) probabilities and predicted any subsequent AUD (OR 8.5, 95% CI 5.4-13.3). An internalizing vulnerability may constitute a pathway to AUD incidence in adolescence and young adulthood. In contrast, no indication for a role of internalizing comorbidity profiles in AUD-stability was found, which may indicate a limited importance of such profiles - in contrast to SUD-related profiles - in AUD stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Temperament and Character Profiles of Sasang Typology in an Adult Clinical Sample

    Directory of Open Access Journals (Sweden)

    Soo Hyun Park

    2011-01-01

    Full Text Available The purpose of this study was to examine the biopsychological personality profiles of traditional Korean Sasang typology based on the Temperament and Character Inventory (TCI in a Korean adult clinical sample. A total of 97 adults completed the Korean version of the TCI. The participants were classified as one of three traditional Korean Sasang types (31 So-Yang, 41 Tae-Eum, 25 So-Eum by three specialists in Sasang typology. The seven dimensions of TCI were compared between the different Sasang types using analysis of variance (ANOVA and profile analysis. There were no significant differences in age, gender and education across the Sasang types. The TCI profile for each of the Sasang types was significantly different (profile analysis, df = 5.038, F = 3.546, P = .004. There were significant differences in the temperament dimensions of Novelty Seeking (F = 3.43, P = .036 and Harm Avoidance (F = 5.43, P = .006 among the Sasang types. The Novelty Seeking score of the So-Yang type (31.90 ± 9.87 was higher than that of the So-Eum type (25.24 ± 9.21; P = .019 while the So-Eum type (44.64 ± 8.47 scored higher on the Harm Avoidance score compared to the So-Yang type (35.16 ± 11.50; P = .003. There were no significant differences in the temperament dimension of Reward Dependence and Persistence, and the three character dimensions of Self-Directedness, Cooperativeness and Self-Transcendence. Results demonstrated distinct temperament traits associated with traditional Korean Sasang types using an objective biopsychological personality inventory. With further study, the Sasang typology may lead to enhanced clinical safety and efficacy as part of personalized medicine with traditional medicine.

  3. Omics AnalySIs System for PRecision Oncology (OASISPRO): A Web-based Omics Analysis Tool for Clinical Phenotype Prediction.

    Science.gov (United States)

    Yu, Kun-Hsing; Fitzpatrick, Michael R; Pappas, Luke; Chan, Warren; Kung, Jessica; Snyder, Michael

    2017-09-12

    Precision oncology is an approach that accounts for individual differences to guide cancer management. Omics signatures have been shown to predict clinical traits for cancer patients. However, the vast amount of omics information poses an informatics challenge in systematically identifying patterns associated with health outcomes, and no general-purpose data-mining tool exists for physicians, medical researchers, and citizen scientists without significant training in programming and bioinformatics. To bridge this gap, we built the Omics AnalySIs System for PRecision Oncology (OASISPRO), a web-based system to mine the quantitative omics information from The Cancer Genome Atlas (TCGA). This system effectively visualizes patients' clinical profiles, executes machine-learning algorithms of choice on the omics data, and evaluates the prediction performance using held-out test sets. With this tool, we successfully identified genes strongly associated with tumor stage, and accurately predicted patients' survival outcomes in many cancer types, including mesothelioma and adrenocortical carcinoma. By identifying the links between omics and clinical phenotypes, this system will facilitate omics studies on precision cancer medicine and contribute to establishing personalized cancer treatment plans. This web-based tool is available at http://tinyurl.com/oasispro ;source codes are available at http://tinyurl.com/oasisproSourceCode .

  4. Metataxonomic profiling and prediction of functional behaviour of wheat straw degrading microbial consortia.

    Science.gov (United States)

    Jiménez, Diego Javier; Dini-Andreote, Francisco; van Elsas, Jan Dirk

    2014-01-01

    Mixed microbial cultures, in which bacteria and fungi interact, have been proposed as an efficient way to deconstruct plant waste. The characterization of specific microbial consortia could be the starting point for novel biotechnological applications related to the efficient conversion of lignocellulose to cello-oligosaccharides, plastics and/or biofuels. Here, the diversity, composition and predicted functional profiles of novel bacterial-fungal consortia are reported, on the basis of replicated aerobic wheat straw enrichment cultures. In order to set up biodegradative microcosms, microbial communities were retrieved from a forest soil and introduced into a mineral salt medium containing 1% of (un)treated wheat straw. Following each incubation step, sequential transfers were carried out using 1 to 1,000 dilutions. The microbial source next to three sequential batch cultures (transfers 1, 3 and 10) were analyzed by bacterial 16S rRNA gene and fungal ITS1 pyrosequencing. Faith's phylogenetic diversity values became progressively smaller from the inoculum to the sequential batch cultures. Moreover, increases in the relative abundances of Enterobacteriales, Pseudomonadales, Flavobacteriales and Sphingobacteriales were noted along the enrichment process. Operational taxonomic units affiliated with Acinetobacter johnsonii, Pseudomonas putida and Sphingobacterium faecium were abundant and the underlying strains were successfully isolated. Interestingly, Klebsiella variicola (OTU1062) was found to dominate in both consortia, whereas K. variicola-affiliated strains retrieved from untreated wheat straw consortia showed endoglucanase/xylanase activities. Among the fungal players with high biotechnological relevance, we recovered members of the genera Penicillium, Acremonium, Coniochaeta and Trichosporon. Remarkably, the presence of peroxidases, alpha-L-fucosidases, beta-xylosidases, beta-mannases and beta-glucosidases, involved in lignocellulose degradation, was indicated

  5. Violence risk prediction. Clinical and actuarial measures and the role of the Psychopathy Checklist.

    Science.gov (United States)

    Dolan, M; Doyle, M

    2000-10-01

    Violence risk prediction is a priority issue for clinicians working with mentally disordered offenders. To review the current status of violence risk prediction research. Literature search (Medline). Key words: violence, risk prediction, mental disorder. Systematic/structured risk assessment approaches may enhance the accuracy of clinical prediction of violent outcomes. Data on the predictive validity of available clinical risk assessment tools are based largely on American and North American studies and further validation is required in British samples. The Psychopathy Checklist appears to be a key predictor of violent recidivism in a variety of settings. Violence risk prediction is an inexact science and as such will continue to provoke debate. Clinicians clearly need to be able to demonstrate the rationale behind their decisions on violence risk and much can be learned from recent developments in research on violence risk prediction.

  6. The clinical profile of employees with mental health problems working in social firms in the UK.

    Science.gov (United States)

    Milton, Alyssa; Parsons, Nicholas; Morant, Nicola; Gilbert, Eleanor; Johnson, Sonia; Fisher, Adrian; Singh, Swaran; Cunliffe, Di; Marwaha, Steven

    2015-08-01

    UK social firms are under-researched but are a potentially important vocational option for people with mental health problems. To describe the clinical profile, satisfaction levels and experiences of social firms employees with mental health problems. Clinical, work and service use characteristics were collected from social firms' employees with mental health problems in England and Wales. Workplace experience and satisfaction were explored qualitatively. Predominantly, social firms' employees (N = 80) report that they have a diagnosis of depression (56%) and anxiety (41%). People with schizophrenia (20%) or bipolar disorder (5%) were a minority. Respondents had low symptom and disability levels, high quality of life and job satisfaction and experienced reductions in secondary mental health service use over time. High-workplace satisfaction was related to flexibility, manager and colleague support and workplace accommodations. The clinical profile, quality of life and job satisfaction level of employees with mental health problems suggest social firms could be a useful addition to UK vocational services for some people. Current employees mainly have common mental disorders, and social firms will need to shift their focus if they are to form a substantial pathway for the vocational recovery of people currently using community mental health teams.

  7. [Cognitive impairment, nutritional status and clinical profile in chronic obstructive pulmonary disease].

    Science.gov (United States)

    López Torres, Isabel; Torres-Sánchez, Irene; Martín Salvador, Adelina; Ortiz Rubio, Araceli; Rodríguez Alzueta, Elisabeth; Valenza, Marie Carmen

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is a progressive disease with a prevalence that increases with the aging of the subject. It presents a high prevalence of comorbidities, such as cognitive decline, which is gaining great clinical relevance in recent years. Factors such as pulmonary function, hypoxemia, hypercapnia or exacerbations contribute to the decline of cognitive functions. The nutritional status has been added to these factors as contributing to cognitive function decline when presenting in COPD. To evidence the relationship between cognitive decline, nutritional status and the clinical profile of patients admitted because of an acute exacerbation of COPD (AECOPD). 110 subjects hospitalized because of COPD, divided in two groups according to their nutritional status and assessment of cognitive decline at admittance, nutritional status and clinical profile. Significant differences between groups concerning nutritional status in anthropometric variables (sex and IMC), functional ability (Barthel index and Daily Life Activities Scale), quality of life (Euroqol- 5D y SGRQ), sleep quality (Pittsburgh), mood (HAD) and cognitive decline (MoCa attention, MoCa abstraction). (pCognitive function is affected in COPD patients with an altered nutritional status when compared to those with a normal nutritional status. The nutritional decline is a factor contributing to the impairment of cognitive functions in this kind of patients, particularly a decline in attention and abstraction ability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  8. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia.

    Science.gov (United States)

    Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

    2015-01-01

    Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response.

  9. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

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    Alberto Tobón-Castaño

    2015-01-01

    Full Text Available Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%, 313 with P. vivax infection (35.2%, and 19 with mixed infection by these species (2.1%. Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54% followed by monocytosis (11%; the differential granulocyte count in 298 patients revealed eosinophilia (15% and high basophil counts (8%. Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response.

  10. Distinguishing predictive profiles for patient-based risk assessment and diagnostics of plaque induced, surgically and prosthetically triggered peri-implantitis.

    Science.gov (United States)

    Canullo, Luigi; Tallarico, Marco; Radovanovic, Sandro; Delibasic, Boris; Covani, Ugo; Rakic, Mia

    2016-10-01

    To investigate whether specific predictive profiles for patient-based risk assessment/diagnostics can be applied in different subtypes of peri-implantitis. This study included patients with at least two implants (one or more presenting signs of peri-implantitis). Anamnestic, clinical, and implant-related parameters were collected and scored into a single database. Dental implant was chosen as the unit of analysis, and a complete screening protocol was established. The implants affected by peri-implantitis were then clustered into three subtypes in relation to the identified triggering factor: purely plaque-induced or prosthetically or surgically triggered peri-implantitis. Statistical analyses were performed to compare the characteristics and risk factors between peri-implantitis and healthy implants, as well as to compare clinical parameters and distribution of risk factors between plaque, prosthetically and surgically triggered peri-implantitis. The predictive profiles for subtypes of peri-implantitis were estimated using data mining tools including regression methods and C4.5 decision trees. A total of 926 patients previously treated with 2812 dental implants were screened for eligibility. Fifty-six patients (6.04%) with 332 implants (4.44%) met the study criteria. Data from 125 peri-implantitis and 207 healthy implants were therefore analyzed and included in the statistical analysis. Within peri-implantitis group, 51 were classified as surgically triggered (40.8%), 38 as prosthetically triggered (30.4%), and 36 as plaque-induced (28.8%) peri-implantitis. For peri-implantitis, 51 were associated with surgical risk factor (40.8%), 38 with prosthetic risk factor (30.4%), 36 with purely plaque-induced risk factor (28.8%). The variables identified as predictors of peri-implantitis were female sex (OR = 1.60), malpositioning (OR = 48.2), overloading (OR = 18.70), and bone reconstruction (OR = 2.35). The predictive model showed 82.35% of accuracy and

  11. Term-tissue specific models for prediction of gene ontology biological processes using transcriptional profiles of aging in drosophila melanogaster

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    Zou Sige

    2008-02-01

    Full Text Available Abstract Background Predictive classification on the base of gene expression profiles appeared recently as an attractive strategy for identifying the biological functions of genes. Gene Ontology (GO provides a valuable source of knowledge for model training and validation. The increasing collection of microarray data represents a valuable source for generating functional hypotheses of uncharacterized genes. Results This study focused on using support vector machines (SVM to predict GO biological processes from individual or multiple-tissue transcriptional profiles of aging in Drosophila melanogaster. Ten-fold cross validation was implemented to evaluate the prediction. One-tail Fisher's exact test was conducted on each cross validation and multiple testing was addressed using BH FDR procedure. The results showed that, of the 148 pursued GO biological processes, fifteen terms each had at least one model with FDR-adjusted p-value (Adj.p Conclusion We proposed the concept of term-tissue specific models indicating the fact that the major part of the optimized prediction models was trained from individual tissue data. Furthermore, we observed that the memberships of the genes involved in all the three pursued children biological processes on mitochondrial electron transport could be predicted from the transcriptional profiles of aging (Adj.p

  12. Changes in cytokine profile may predict therapeutic efficacy of infliximab in patients with ulcerative colitis.

    Science.gov (United States)

    Sato, Shoko; Chiba, Toshimi; Nakamura, Shotaro; Matsumoto, Takayuki

    2015-10-01

    Infliximab is an established therapy for ulcerative colitis (UC). The aim of this study was to examine various serum cytokine levels and to identify possible markers predictive of therapeutic efficacy of infliximab for UC patients. Twenty-one patients with moderately active UC were given intravenous infliximab (5 mg/kg) at 0, 2, and 6 weeks as induction therapy. The serum levels of 17 cytokines were determined using a Bio-Plex suspension array system before and 8 weeks after induction therapy. Partial Mayo score (PMS) and serum C-reactive protein levels were used for the determination of clinical activities at 0 and 8 weeks after the treatment. The overall therapeutic effect was determined at 26 weeks according to the PMS. The median value of the PMS decreased significantly 8 weeks after the treatment (from 6 to 1.5, P infliximab, while IL-6 at 8 weeks after induction therapy may be predictive of subsequent response to infliximab. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  13. Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

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    Huang Chi-Cheng

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

  14. Sterile paper points as a bacterial DNA-contamination source in microbiome profiles of clinical samples.

    Science.gov (United States)

    van der Horst, Joyce; Buijs, Mark J; Laine, Marja L; Wismeijer, Daniël; Loos, Bruno G; Crielaard, Wim; Zaura, Egija

    2013-12-01

    High throughput sequencing of bacterial DNA from clinical samples provides untargeted, open-ended information on the entire microbial community. The downside of this approach is the vulnerability to DNA contamination from other sources than the clinical sample. Here we describe contamination from sterile paper points (PPs) used in microbial sample collection. Peri-implant samples from 48 individuals were collected using sterile PPs. Control samples contained only PPs or DNA extraction blank controls. 16S rRNA gene libraries were sequenced using 454 pyrosequencing. 16S rRNA gene copy numbers were measured by quantitative PCR. Nearly half of the sequencing reads belonged to two OTUs classified as Enterococcus (25% of reads) or Exiguobacterium (21%), which are not typical oral microorganisms. Of 87 peri-implant samples, only 10 samples (11%) contained neither of the two OTUs. The relative abundance of both unusual OTUs correlated with each other (pDNA equivalent to 1.2 × 10(3) and 1.1 × 10(4) cells respectively, which was within the range of DNA in the clinical samples (average 1.8 × 10(7), SD 4.8 × 10(7), min 4.4 × 10(2), max 2.8 × 10(8)). The microbial profile from these PPs was dominated (>83% of reads) by the two unusual OTUs. Sterile PPs can contain contaminating bacterial DNA. The use of PPs as a sampling tool for microbial profiling of clinical samples by open-ended techniques such as sequencing or DGGE should be avoided. Clinicians working with PPs as sampling tools for bacterial DNA should consider using an alternative sampling tool, because sterile unused PPs can be a considerable source of foreign bacterial DNA. We recommend sterile curettes for collecting clinical samples for open-ended techniques, such as sequencing or DGGE. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. SPECIFICITIES OF THE SUBSET PROFILE OF PERIPHERAL BLOOD IN PATIENTS WITH GLIOBLASTOMA: PATHOGENETIC AND CLINICAL ASSESSMENTS

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    V. A. Chumakov

    2006-01-01

    Full Text Available Abstract. In glioblastoma (GB, it is necessary to take into consideration GB-associated secondary immunodeficiency (SID, so-called syndrome of tumor-associated SID (STASID. Cell subsets having effector and regulatory functions, play an important role in developing STASID, and their proportions in patients with different forms of GB can be of pathogenetic importance and have clinical value for treatment and rehabilitation scheduling as well. The most pathogenically and clinically important features of cell subsets profile of peripheral blood were analyzed in patients with different clinical and morphological types of GB. The patients were divided into three groups, i.e., groups I and II were formed by patients with STASID (marked and slightly marked SID, accordingly; group III – patients with SIDTAS (tumor-associated autoimmune syndrome, associated with SID. Marked suppression of cell immunity is typical of group I - imbalance in T-lymphocytes, in a number of specific subsets, and in subsets clusters, as well as disproportions in the immunoregulatory indexes. In group II, the subset profiles of blood were slightly different from the norm. In patients with SIDTAS, activation of cell immunity was evident, forming SID with signs of autoimmune syndrome, affecting effector and regulatory chains of immunity, and influencing the severity and forecast of the disease. Specific features of the immune status in patients with GB identified can be resulted from different clinicalmorphological types of the tumor; the latter are to be considered in differential diagnostics of clinical course of GB and in scheduling of clinical-immunological efficient anti-tumor pharmacotherapy in pre- and postoperative periods.

  16. Evaluating the molecule-based prediction of clinical drug responses in cancer.

    Science.gov (United States)

    Ding, Zijian; Zu, Songpeng; Gu, Jin

    2016-10-01

    Molecule-based prediction of drug response is one major task of precision oncology. Recently, large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), provide the opportunity to evaluate the predictive utility of molecular data for clinical drug responses in multiple cancer types. Here, we first curated the drug treatment information from TCGA. Four chemotherapeutic drugs had more than 180 clinical response records. Then, we developed a computational framework to evaluate the molecule based predictions of clinical responses of the four drugs and to identify the corresponding molecular signatures. Results show that mRNA or miRNA expressions can predict drug responses significantly better than random classifiers in specific cancer types. A few signature genes are involved in drug response related pathways, such as DDB1 in DNA repair pathway and DLL4 in Notch signaling pathway. Finally, we applied the framework to predict responses across multiple cancer types and found that the prediction performances get improved for cisplatin based on miRNA expressions. Integrative analysis of clinical drug response data and molecular data offers opportunities for discovering predictive markers in cancer. This study provides a starting point to objectively evaluate the molecule-based predictions of clinical drug responses. jgu@tsinghua.edu.cn 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.

  17. Comparative study of clinical profile of lean and obese polycystic ovary syndrome women

    OpenAIRE

    Akshaya S.; Ratnaboli Bhattacharya

    2016-01-01

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, with an estimated prevalence of 4-8% and is the most frequent cause of oligoanovulatory infertility. The objective was to compare the clinical profile of PCOS in lean PCOS (body mass index (BMI) 23 kg/m2) women. Methods: Fifty healthy women who were euthyroid with age range 15-38 years who presented to gynecology OPD and diagnosed to have PCOS according to ESHRE/ASRM criteria were...

  18. Low vitamin D levels predict clinical features of schizophrenia.

    Science.gov (United States)

    Cieslak, Kristina; Feingold, Jordyn; Antonius, Daniel; Walsh-Messinger, Julie; Dracxler, Roberta; Rosedale, Mary; Aujero, Nicole; Keefe, David; Goetz, Deborah; Goetz, Raymond; Malaspina, Dolores

    2014-11-01

    Vitamin D plays crucial roles in neuroprotection and neurodevelopment, and low levels are commonly associated with schizophrenia. We considered if the association was spurious or causal by examining the association of Vitamin D with Leukocyte Telomere Length (LTL), a marker of cellular aging. Vitamin D levels in 22 well-characterized schizophrenia cases were examined with respect to symptoms, cognition, and functioning. LTL was assessed using quantitative polymerase chain reaction (qPCR). The results showed that 91% (20) had deficient or insufficient Vitamin D levels, which were associated with excitement and grandiosity, social anhedonia, and poverty of speech. Sex-specific analyses showed strong associations of hypovitamintosis D to negative symptoms and decreased premorbid adjustment in males, and to lesser hallucinations and emotional withdrawal, but increased anti-social aggression in females. In females LTL was furthermore associated with Vitamin D levels. This study demonstrates a relationship of low vitamin D levels with increased cellular aging in females. It is also the first study to demonstrate potential sex-specific profiles among schizophrenia cases with hypovitaminosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The clinical trial landscape in oncology and connectivity of somatic mutational profiles to targeted therapies.

    Science.gov (United States)

    Patterson, Sara E; Liu, Rangjiao; Statz, Cara M; Durkin, Daniel; Lakshminarayana, Anuradha; Mockus, Susan M

    2016-01-16

    Precision medicine in oncology relies on rapid associations between patient-specific variations and targeted therapeutic efficacy. Due to the advancement of genomic analysis, a vast literature characterizing cancer-associated molecular aberrations and relative therapeutic relevance has been published. However, data are not uniformly reported or readily available, and accessing relevant information in a clinically acceptable time-frame is a daunting proposition, hampering connections between patients and appropriate therapeutic options. One important therapeutic avenue for oncology patients is through clinical trials. Accordingly, a global view into the availability of targeted clinical trials would provide insight into strengths and weaknesses and potentially enable research focus. However, data regarding the landscape of clinical trials in oncology is not readily available, and as a result, a comprehensive understanding of clinical trial availability is difficult. To support clinical decision-making, we have developed a data loader and mapper that connects sequence information from oncology patients to data stored in an in-house database, the JAX Clinical Knowledgebase (JAX-CKB), which can be queried readily to access comprehensive data for clinical reporting via customized reporting queries. JAX-CKB functions as a repository to house expertly curated clinically relevant data surrounding our 358-gene panel, the JAX Cancer Treatment Profile (JAX CTP), and supports annotation of functional significance of molecular variants. Through queries of data housed in JAX-CKB, we have analyzed the landscape of clinical trials relevant to our 358-gene targeted sequencing panel to evaluate strengths and weaknesses in current molecular targeting in oncology. Through this analysis, we have identified patient indications, molecular aberrations, and targeted therapy classes that have strong or weak representation in clinical trials. Here, we describe the development and disseminate

  20. Design-phase prediction of potential cancer clinical trial accrual success using a research data mart.

    Science.gov (United States)

    London, Jack W; Balestrucci, Luanne; Chatterjee, Devjani; Zhan, Tingting

    2013-12-01

    Many cancer interventional clinical trials are not completed because the required number of eligible patients are not enrolled. To assess the value of using a research data mart (RDM) during the design of cancer clinical trials as a predictor of potential patient accrual, so that less trials fail to meet enrollment requirements. The eligibility criteria for 90 interventional cancer trials were translated into i2b2 RDM queries and cohort sizes obtained for the 2 years prior to the trial initiation. These RDM cohort numbers were compared to the trial accrual requirements, generating predictions of accrual success. These predictions were then compared to the actual accrual performance to evaluate the ability of this methodology to predict the trials' likelihood of enrolling sufficient patients. Our methodology predicted successful accrual (specificity) with 0.969 (=31/32 trials) accuracy (95% CI 0.908 to 1) and predicted failed accrual (sensitivity) with 0.397 (=23/58 trials) accuracy (95% CI 0.271 to 0.522). The positive predictive value, or precision rate, is 0.958 (=23/24) (95% CI 0.878 to 1). A prediction of 'failed accrual' by this methodology is very reliable, whereas a prediction of accrual success is less so, as causes of accrual failure other than an insufficient eligible patient pool are not considered. The application of this methodology to cancer clinical design would significantly improve cancer clinical research by reducing the costly efforts expended initiating trials that predictably will fail to meet accrual requirements.

  1. Predicting Delirium Duration in Elderly Hip-Surgery Patients: Does Early Symptom Profile Matter?

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    Chantal J. Slor

    2013-01-01

    Full Text Available Background. Features that may allow early identification of patients at risk of prolonged delirium, and therefore of poorer outcomes, are not well understood. The aim of this study was to determine if preoperative delirium risk factors and delirium symptoms (at onset and clinical symptomatology during the course of delirium are associated with delirium duration. Methods. This study was conducted in prospectively identified cases of incident delirium. We compared patients experiencing delirium of short duration (1 or 2 days with patients who had more prolonged delirium (≥3 days with regard to DRS-R-98 (Delirium Rating Scale Revised-98 symptoms on the first delirious day. Delirium symptom profile was evaluated daily during the delirium course. Results. In a homogenous population of 51 elderly hip-surgery patients, we found that the severity of individual delirium symptoms on the first day of delirium was not associated with duration of delirium. Preexisting cognitive decline was associated with prolonged delirium. Longitudinal analysis using the generalised estimating equations method (GEE identified that more severe impairment of long-term memory across the whole delirium episode was associated with longer duration of delirium. Conclusion. Preexisting cognitive decline rather than severity of individual delirium symptoms at onset is strongly associated with delirium duration.

  2. Prediction of neonates' macrosomia with maternal lipid profile of healthy mothers.

    Science.gov (United States)

    Mossayebi, Elaheh; Arab, Zohreh; Rahmaniyan, Mojgan; Almassinokiani, Fariba; Kabir, Ali

    2014-02-01

    The aim of this study is to identify the association between the lipid profile of healthy nondiabetic, nonobese pregnant women in the first weeks of the third trimester of pregnancy and macrosomia or large-for-gestational-age (LGA) neonates with normal pregnancies. In this cohort study, 200 pregnant healthy women without gestational diabetes mellitus (GDM), obesity, or hypertension and carrying a single fetus in a prenatal clinic of a referral hospital were included based on a convenience sampling. Then, we took a blood sample to assess fasting blood sugar (FBS), triglyceride (TG), total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). GDM was assessed after administering 50 g of oral glucose. All cases were followed until the end of pregnancy. The main outcome measurement was neonatal birth weight. Only 154 mothers met eligibility criteria. There were eight cases (5.2%) with macrosomia (birth weight ≥ 4000 g) and 35 cases (22.7%) with LGA. Linear regression showed that mothers' TG and neonates' gender were independent predictors of the birth weight of the children (R-square = 0.52, p macrosomia (Nagelkerke R-square = 0.53, p macrosomia (birth weight > 4500 g), but also for LGA. Copyright © 2013. Published by Elsevier B.V.

  3. Current and Future Applications of Biomedical Engineering for Proteomic Profiling: Predictive Biomarkers in Neuro-Traumatology

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    Mario Ganau

    2018-02-01

    Full Text Available This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers in patients with traumatic brain injury (TBI, a critical worldwide health problem with an estimated 10 billion people affected annually worldwide. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials. Only experimental articles revolving around the management of TBI, in which the role of new devices based on innovative discoveries coming from the field of nanotechnology and biomedical engineering were highlighted, have been included and analyzed in this study. Based on theresults gathered from this research on innovative methods for genomics, epigenomics, and proteomics, their future application in this field seems promising. Despite the outstanding technical challenges of identifying reliable biosignatures for TBI and the mixed nature of studies herein described (single cells proteomics, biofilms, sensors, etc., the clinical implementation of those discoveries will allow us to gain confidence in the use of advanced neuromonitoring modalities with a potential dramatic improvement in the management of those patients.

  4. Clinical and radiologic predictive factors of septic hip arthritis.

    Science.gov (United States)

    Kung, Justin W; Yablon, Corrie; Huang, Edward S; Hennessey, Hooman; Wu, Jim S

    2012-10-01

    The purpose of our study was to identify the clinical and radiologic factors associated with a positive culture during image-guided hip joint aspiration. We performed a retrospective analysis of 167 consecutive hip aspirations for septic arthritis at a large tertiary medical center. Chart review was performed on the following clinical factors: serum WBC count≥11×10(3)/μL, serum erythrocyte sedimentation rate (ESR)≥20 mm/h, C-reactive protein (CRP)≥100 mg/L, synovial fluid WBC count, synovial fluid polymorphonuclear (PMN) leukocytes≥90%, fever, immunosuppression, antibiotic use, diabetes, presence of a prosthesis, and IV drug use (IVDU). Radiologic studies were reviewed for the following imaging and technical factors: presence of a sinus tract, fluid turbidity, volume of fluid (mL) aspirated, and whether the fluid analyzed was primarily aspirated or reaspirated after lavage. Logistic regression was used to calculate odds ratio (OR) and 95% CI. Of the 167 aspirations, 29 (17.4%) had positive cultures; 6 of 29 (20.7%) positive cultures occurred in reaspirated lavage fluid. On multivariate analysis using logistic regression with stepwise backward elimination, the significant clinical and radiologic predictors were elevated WBC (OR, 4.4; 95% CI, 1.1-17.3), high percentage of synovial fluid PMN leukocytes (OR, 10.6; 95% CI, 2.9-39.8), IVDU (OR, 9.0; 95% CI, 1.3-64.7), and fluid turbidity (OR, 20.5; 95% CI, 6.9-61.4). Positive hip cultures are associated with elevated serum WBC, IVDU, high percentage of synovial fluid PMN leukocytes, and fluid aspirate turbidity. Reaspiration of lavage fluid with either nonbacteriostatic saline or contrast material can yield positive cultures.

  5. Evaluation of clinical, laboratory, and electrophoretic profiles for diagnosis of malnutrition in hospitalized dogs

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    Andrei Kelliton Fabretti

    2015-02-01

    Full Text Available Malnutrition is a major factor associated with increased rates of mortality and readmission, longer hospital stays, and greater health care spending. Recognizing malnourished or at-risk animals allows for nutritional intervention and improved prognosis. This study evaluated the association between clinical, laboratory, and electrophoretic variables and the nutritional status (NS of hospitalized dogs in order to generate a profile of the sick dog and to facilitate the diagnosis of malnutrition. We divided 215 dogs into groups according to the severity of the underlying disease and we determined the clinical NS based on the assessment of the body condition score and the muscle mass score. The NS was classified as clinically well nourished, clinical moderate malnutrition, or clinical severe malnutrition. Statistical analyses were conducted by using the chi-square test or Fisher’s exact test; the Kruskal-Wallis test was used for continuous variables. A strong association was found between malnutrition and the severity of the underlying disease. In hospitalized dogs, low body mass index values, anemia, low hemoglobin concentrations, high fibrinogen concentrations, decreased albumin fraction, and increased gamma-globulin fraction (in electrophoresis were associated with malnutrition, reinforcing the classification of poor NS. However, the skin and coat characteristics, the total number of lymphocytes, blood glucose, cholesterol, and total protein concentration were not found to be good predictors of NS.

  6. Prediction of glycated hemoglobin levels at 3 months after metabolic surgery based on the 7-day plasma metabolic profile.

    Directory of Open Access Journals (Sweden)

    Hyuk Nam Kwon

    Full Text Available Metabolic surgery has been shown to provide better glycemic control for type 2 diabetes than conventional therapies. Still, the outcomes of the surgery are variable, and prognostic markers reflecting the metabolic changes by the surgery are yet to be established. NMR-based plasma metabolomics followed by multivariate regression was used to test the correlation between the metabolomic profile at 7-days after surgery and glycated hemoglobin (HbA1c levels at 3-months (and up to 12 months with less patients, and to identify the relevant markers. Metabolomic profiles at 7-days could differentiate the patients according to the HbA1c improvement status at 3-months. The HbA1c values were predicted based on the metabolomics profile with partial least square regression, and found to be correlated with the observed values. Metabolite analysis suggested that 3-Hydroxybutyrate (3-HB and glucose contributes to this prediction, and the [3-HB]/[glucose] exhibited a modest to good correlation with the HbA1c level at 3-months. The prediction of 3-month HbA1c using 7-day metabolomic profile and the suggested new criterion [3-HB]/[glucose] could augment current prognostic modalities and help clinicians decide if drug therapy is necessary.

  7. Clinical prediction model to identify vulnerable patients in ambulatory surgery: towards optimal medical decision-making

    NARCIS (Netherlands)

    H. Mijderwijk (Herjan); R.J. Stolker (Robert); H.J. Duivenvoorden (Hugo); M. Klimek (Markus); E.W. Steyerberg (Ewout)

    2016-01-01

    markdownabstract__Background:__ Ambulatory surgery patients are at risk of adverse psychological outcomes such as anxiety, aggression, fatigue, and depression. We developed and validated a clinical prediction model to identify patients who were vulnerable to these psychological outcome parameters.

  8. Prenatal prediction of pulmonary hypoplasia: clinical, biometric, and Doppler velocity correlates

    NARCIS (Netherlands)

    J.A.M. Laudij (Jacqueline); D. Tibboel (Dick); S.G.F. Robben (Simon); R.R. de Krijger (Ronald); M.A.J. de Ridder (Maria); J.W. Wladimiroff (Juriy)

    2002-01-01

    textabstractOBJECTIVES: To determine the value of pulmonary artery Doppler velocimetry relative to fetal biometric indices and clinical correlates in the prenatal prediction of lethal lung hypoplasia (LH) in prolonged (>1 week) oligohydramnios. METHODS: Forty-two singleton

  9. Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

    Science.gov (United States)

    Palomba, Stefano; Falbo, Angela; Chiossi, Giuseppe; Muscogiuri, Giovanna; Fornaciari, Eleonora; Orio, Francesco; Tolino, Achille; Colao, Annamaria; La Sala, Giovanni Battista; Zullo, Fulvio

    2014-10-01

    Alterations in lipid pattern and increased risk for obstetric/neonatal complications have been observed in patients with polycystic ovary syndrome (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and alterations in lipid profile have been related with adverse pregnancy outcomes. Based on these considerations, the aim of the present prospective controlled clinical study was to test the hypothesis that the changes in the lipid profile in patients with PCOS during pregnancy are characteristic and potentially related to the increased risk of obstetric/neonatal complications. One hundred and fifty nonobese PCOS women and 150 age- and body mass index (BMI)-matched healthy controls were enrolled. Serum lipids, glucose, insulin, and androgens levels were serially assayed in all subjects before and throughout pregnancy. Serum low-density lipoprotein (LDL) and triglyceride (TG) concentrations were significantly (Plipid levels, body weight gain, and insulin-resistance markers, serum TG concentrations during pregnancy were directly and independently associated with obstetric complications in both groups, whereas serum LDL levels only in PCOS patients. We can conclude that nonobese PCOS patients had specific changes in lipid profile during pregnancy, and that the lipid pattern typical of PCOS may account for the more frequent adverse pregnancy outcomes. PCOS-related hormonal and metabolic features, such as insulin resistance and high androgen levels, may mediate this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Non-invasive metabolomic profiling of embryo culture media and morphology grading to predict implantation outcome in frozen-thawed embryo transfer cycles.

    Science.gov (United States)

    Li, Xiong; Xu, Yan; Fu, Jing; Zhang, Wen-Bi; Liu, Su-Ying; Sun, Xiao-Xi

    2015-11-01

    Assessment of embryo viability is a crucial component of in vitro fertilization and currently relies largely on embryo morphology and cleavage rate. Because morphological assessment remains highly subjective, it can be unreliable in predicting embryo viability. This study investigated the metabolomic profiling of embryo culture media using near-infrared (NIR) spectroscopy for predicting the implantation potential of human embryos in frozen-thawed embryo transfer (FET) cycles. Spent embryo culture media was collected on day 4 after thawed embryo transfer (n = 621) and analysed using NIR spectroscopy. Viability scores were calculated using a predictive multivariate algorithm of fresh embryos with known pregnancy outcomes. The mean viability indices of embryos resulting in clinical pregnancy following FET were significantly higher than those of non-implanted embryos and differed between the 0, 50, and 100 % implantation groups. Notably, the 0 % group index was significantly lower than the 100 % implantation group index (-0.787 ± 0.382 vs. 1.064 ± 0.331, P  0.05). NIR metabolomic profiling of thawed embryo culture media is independent of morphology and correlates with embryo implantation potential in FET cycles. The viability score alone or in conjunction with morphologic grading is a more objective marker for implantation outcome in FET cycles than morphology alone.

  11. Predicting pressure ulcers: cases missed using a new clinical prediction rule.

    NARCIS (Netherlands)

    Schoonhoven, L.; Grobbee, D.E.; Bousema, M.T.; Buskens, E.

    2005-01-01

    AIM: The aim of this paper is to report a study describing patients with pressure ulcers that were incorrectly classified as 'not at risk' by the prediction rule and comparing them with patients who were correctly classified as 'not at risk'. BACKGROUND: Patients admitted to hospital are at risk of

  12. Clinical Prediction Making: Examining Influential Factors Related to Clinician Predictions of Recidivism among Juvenile Offenders

    Science.gov (United States)

    Calley, Nancy G.; Richardson, Emily M.

    2011-01-01

    This study examined factors influencing clinician predictions of recidivism for juvenile offenders, including youth age at initial juvenile justice system involvement, youth age at discharge, program completion status, clinician perception of strength of the therapeutic relationship, and clinician perception of youth commitment to treatment.…

  13. Epidemiological profile of colombian patients with rheumatoid arthritis in a specialized care clinic.

    Science.gov (United States)

    Bautista-Molano, Wilson; Fernández-Avila, Daniel; Jiménez, Ruth; Cardozo, Rosa; Marín, Andrés; Soler, María Del Pilar; Gómez, Olga; Ruiz, Oscar

    Few studies report the epidemiological profile of RA patients attending clinics for comprehensive care. We describe the clinical, socio-demographic characteristics and comorbidities of a cohort of patients with RA. Cross-sectional study in a cohort of patients according to ACR criteria/EULAR 2010 classification who have entered to the AR clinic since October 2012 until May 2014, referred from primary care. Frequencies for socio-demographic, comorbidity, state of disease activity, functional status, biomarkers and therapeutic modalities variables are described. In total, 1652 patients were included with a mean age of 58 years and a duration of 9 years. Rheumatoid factor was positive in 80% and anti-citrullinated peptide antibody in 63% of patients. In total, 43.6% of patients had comorbidities: Hypertension (20.4%), osteoporosis (17.3%) and Sjögren's syndrome (10.4%). Fifty percent of the patients had moderate and high disease activity level measured by DAS-28 score, and the mean HAQ score was 0.64 (DS 1.12). Seventy three percent of patients were treated with oral disease modified anti rheumatic treatment and 63.6% of them were with methotrexate. 42.4% of the patients were treated with glucocorticoids (mean dose 6.3mg). The epidemiological behavior of a group of RA patients is reported. The presence of comorbidities is significant affecting the risk of morbidity and mortality in these patients. The definition of the epidemiological profile of this population will allow the design of research questions to resolve outstanding problems in the clinical context of this pathology. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  14. A study of the clinical profile and outcome of spina bifida

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    Theophilus Nikita Kumar

    2016-02-01

    Full Text Available Neural tube defects (NTDs are a group of congenital anomalies characterized by defects in dorsal midline structures, including neural tissue, dura, muscle, bone and/or skin. The clinical presentations and the follow-up of these patients requires attention to various end organs besides the nervous system. To evaluate the clinical profile and surgical outcome of children with spina bifida. Out of a total of 74 patients treated at our institute for spina bifida between June 2013 to august 2015, 74 cases of spina bifida were analyzed retrospectively and prospectively. The clinical profile, radiological findings and urodynamic studies were recorded. Craniospinal MRI was done in patients to screen for Arnold Chiari malformations and monitoring of hydrocephalus was done as a management protocol at our institute for these children. All these patients except two underwent surgery for correction and closure of the spinal defect. Associated anomalies were treated accordingly. They were clinically assessed over a mean follow up period of 1.3years, ranging from 2months to 2½ years. 73% of the patients presented in the neonatal age group. Of which, 72% presented with a visible sac over the back.72% of the cases were Myelomeningocoeles. 79% of the defects were in the lumbosacral region.30% presented with sensorimotor loss or bladder bowel incontinence. Sensorimotor improvement was seen in 12.5% after repairing the defect with the help of physiotherapy and braces. 30% of the patients were diagnosed to have hydrocephalus, of which 33% required a CSF diversion procedure. The postoperative course of spina bifida repair was found to be uneventful in 90% of the patients

  15. Clinical Profiles and Short-Term Outcomes of Acute Disseminated Encephalomyelitis in Adult Chinese Patients

    Science.gov (United States)

    Yang, Hong-Qi; Zhao, Wen-Cong; Yang, Wei-Min; Li, Yong-Li; Sun, Zhi-Kun; Chen, Shuai

    2016-01-01

    Background and Purpose Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that predominantly affects children. Previous studies have mostly involved children in Western developed countries. Methods This study retrospectively reviewed the clinical profiles of ADEM in adult Chinese patients. Results ADEM occurred during summer and autumn in about two-thirds of the 42 included patients. Prior infection was found in five patients and no preimmunization was recorded. The most frequent clinical presentations were alterations in consciousness (79%) and behavior changes (69%), followed by motor deficits (64%) and fever (50%). About one-quarter (26%) of the patients showed positive results for oligoclonal bands, and about half of them exhibited increases in the IgG index and 24-hour IgG synthesis rate. Magnetic resonance imaging showed white- and gray-matter lesions in 83% and 23% of the patients, respectively. Steroids were the main treatment, and full recovery occurred in 62% of the patients, with residual focal neurological deficits recorded in a few patients. After a mean follow-up period of 3.4 years, two patients exhibited recurrence and one patient exhibited a multiphasic course. One patient was diagnosed with multiple sclerosis (MS). Conclusions With the exception of the seasonal distribution pattern and prior vaccine rate, the clinical profiles of ADEM in adult Chinese patients are similar to those in pediatric populations. No specific markers are available for distinguishing ADEM from MS at the initial presentation. Careful clinical evaluations, cerebrospinal fluid measurements, and neuroradiological examinations with long-term follow-up will aid the correct diagnosis of ADEM. PMID:27449911

  16. Predicting nicotine dependence profiles among adolescent smokers: the roles of personal and social-environmental factors in a longitudinal framework

    Directory of Open Access Journals (Sweden)

    Kleinjan Marloes

    2012-03-01

    Full Text Available Abstract Background Although several studies have reported that symptoms of nicotine dependence can occur after limited exposure to smoking, the majority of research on nicotine dependence has focused on adult smokers. Insufficient knowledge exists regarding the epidemiology and aetiology of nicotine dependence among adolescent smokers. The objective of the present study is to identify the effects of theoretically driven social and individual predictors of nicotine dependence symptom profiles in a population-based sample of adolescent smokers. Method A longitudinal study among 6,783 adolescents (12 to 14 years old at baseline was conducted. In the first and second year of secondary education, personality traits and exposure to smoking in the social environment were assessed. Two and a half years later, adolescents' smoking status and nicotine dependence symptom profiles were assessed. A total of 796 adolescents were identified as smokers and included in the analyses. Results At follow-up, four distinct dependence symptom profiles were identified: low cravings only, high cravings and withdrawal, high cravings and behavioural dependence, and overall highly dependent. Personality traits of neuroticism and extraversion did not independently predict nicotine dependence profiles, whereas exposure to smoking in the social environment posed a risk for the initial development of nicotine dependence symptoms. However, in combination with environmental exposure to smoking, extraversion and neuroticism increased the risk of developing more severe dependence symptom profiles. Conclusions Nicotine dependence profiles are predicted by interactions between personal and environmental factors. These insights offer important directions for tailoring interventions to prevent the onset and escalation of nicotine dependence. Opportunities for intervention programs that target individuals with a high risk of developing more severe dependence symptom profiles are

  17. A circulating TH2 cytokines profile predicts survival in patients with resectable pancreatic adenocarcinoma

    Science.gov (United States)

    Piro, Geny; Carbone, Carmine; Frizziero, Melissa; Malleo, Giuseppe; Zanini, Silvia; Casolino, Raffaella; Santoro, Raffaela; Mina, Maria Mihaela; Zecchetto, Camilla; Merz, Valeria; Scarpa, Aldo; Bassi, Claudio; Tortora, Giampaolo

    2017-01-01

    ABSTRACT Surgery is the only potentially curative option for patients with pancreatic ductal adenocarcinoma (PDAC), but metastatic relapse remains common. We hypothesized that the expression levels of inflammatory cytokines could predict recurrence of PDAC, thus allowing to select patients who most likely could benefit from surgical resection. We prospectively collected plasma at diagnosis from 287 patients with pancreatic resectable neoplasms. The expression levels of 23 cytokines were measured in 90 patients with PDAC by using a multiplex analyte profiling assay. Levels higher than cutoff identified of the TH2 cytokines interleukin (IL)4, IL5, IL6 of macrophage inflammatory protein (MIP)1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)1, and of IL17α, IFNγ-induced protein (IP)10, and IL1b were significantly associated with a shorter median OS. In particular, levels of IL4 and IP10 higher than cutoff identified, and level of TH1 cytokines TNFα and INFγ, and of IL9 and IL1Rα lower than cutoff identified were significantly associated with a shorter DFS. In the multivariate analysis, high IP10 was confirmed as negatively associated with OS (HR = 3.097, p = 0.014) and IL4 and TNFα remain negatively (HR = 2.75, p = 0.002) and positively (HR = 0.224, p = 0.049) associated with DFS, respectively. Simultaneous expression of low IL4 and high TNFα identified patients with best prognosis (HR = 0.313, p < 0.0001). In conclusion, we demonstrated that, among a series of cytokines, IL4 is the most significant independent prognostic factor for DFS in resectable PDAC patients, and it could be useful to select patients with high risk of early recurrence who may avoid an unnecessary resection. PMID:28932629

  18. Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection.

    Directory of Open Access Journals (Sweden)

    Jun Hou

    Full Text Available Chronic hepatitis B is a highly heterogeneous liver disease characterized by phases with fluctuations in viral replication and progressive liver damage in some, but not all infected individuals. Despite four decades of research, insight into host determinants underlying these distinct clinical phases-immunotolerant, immune active, inactive carrier, and HBeAg-negative hepatitis-remains elusive. We performed an in-depth transcriptome analysis of archived FFPE liver biopsies of each clinical phase to address host determinants associated with the natural history. Therefore, we determined, for the first time, intrahepatic global expression profiles of well-characterized chronic HBV patients at different clinical phases. Our data, obtained by microarray, demonstrate that B cells and NK/cytotoxic-related genes in the liver, including CD19, TNFRSF13C, GZMH, and KIR2DS3, were differentially expressed across the clinical HBV phases, which was confirmed by modular analysis and also Nanostring arrays in an independent cohort. Compared to the immunotolerant phase, 92 genes were differentially expressed in the liver during the immune active phase, 46 in the inactive carrier phase, and 71 in the HBeAg-negative phase. Furthermore, our study also revealed distinctive transcription of genes associated with cell cycle activity, NF-κB signaling, cytotoxic function and mitochondrial respiration between clinical phases. Our data define for the first time using microarray unique transcriptomes in the HBV-infected liver during consecutive clinical phases. We demonstrate that fluctuations of viral loads and liver damage coincide with fluctuations in the liver transcriptome and point to functional- immune and non-immune- components contributing to the clinical phenotype in patients.

  19. Neuro-Fuzzy Prediction of Cooperation Interaction Profile of Flexible Road Train Based on Hybrid Automaton Modeling

    Directory of Open Access Journals (Sweden)

    Banjanovic-Mehmedovic Lejla

    2016-01-01

    Full Text Available Accurate prediction of traffic information is important in many applications in relation to Intelligent Transport systems (ITS, since it reduces the uncertainty of future traffic states and improves traffic mobility. There is a lot of research done in the field of traffic information predictions such as speed, flow and travel time. The most important research was done in the domain of cooperative intelligent transport system (C-ITS. The goal of this paper is to introduce the novel cooperation behaviour profile prediction through the example of flexible Road Trains useful road cooperation parameter, which contributes to the improvement of traffic mobility in Intelligent Transportation Systems. This paper presents an approach towards the control and cooperation behaviour modelling of vehicles in the flexible Road Train based on hybrid automaton and neuro-fuzzy (ANFIS prediction of cooperation profile of the flexible Road Train. Hybrid automaton takes into account complex dynamics of each vehicle as well as discrete cooperation approach. The ANFIS is a particular class of the ANN family with attractive estimation and learning potentials. In order to provide statistical analysis, RMSE (root mean square error, coefficient of determination (R2 and Pearson coefficient (r, were utilized. The study results suggest that ANFIS would be an efficient soft computing methodology, which could offer precise predictions of cooperative interactions between vehicles in Road Train, which is useful for prediction mobility in Intelligent Transport systems.

  20. [Clinical and psychopathological profile of women victims of psychological partner violence].

    Science.gov (United States)

    Lamy, C; Dubois, F; Jaafari, N; Carl, T; Gaillard, P; Camus, V; El Hage, W

    2009-08-01

    Partner violence is a serious public health problem, due to their potential short-, medium- or long-term physical and psychological consequences. Violence is unbearable when it occurs between family members, and often remains unrevealed, invisible, hidden and repeated. The woman possibly feels trapped in a relationship of imprisonment. International studies have well-explored the psychopathological aspects of physical and sexual abuse within couples, but few explored the clinical profile of women victims of psychological violence or moral harassment. This study aims to define the clinical and psychopathological profile of women who are victims of psychological intimate partner violence. We contacted 628 women who consulted consecutively at the emergency ward of a university hospital covering a 300,000 catchment area. The telephone screening of psychological violence was therefore carried out using the Women's Experience with Battering (WEB) questionnaire (N=226). An optional clinical interview was given to the women declaring themselves as victims of psychological intimate partner violence (N=56) to evaluate the life events and the psychiatric disorders according to the DSM-IV. Finally, 43 participants (77%) gave their opinion on the qualitative aspects of the WEB questionnaire and their level of ease with this report. In 63% (N=35) of the cases, the victims and their partners had a rather high socioprofessional level. Women refer to emergency ward mostly for complaint of vague idiopathic pain (49%) or for psychiatric disorders (52%) with predominance of anxiety (28%) or addictive disorders (19%). The prevalence of potentially traumatic life events was found to be high in this group (83%). The traumatic psychological intimate partner violence was associated with a heightened prevalence of psychiatric comorbidities, like anxiety (72%), depression (100%), posttraumatic stress disorder (100%), and addiction to alcohol (100%) or another psychoactive substance (50

  1. Usefulness of Clinical Prediction Rules, D-dimer, and Arterial Blood Gas Analysis to Predict Pulmonary Embolism in Cancer Patients

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    Shazia Awan

    2017-03-01

    Full Text Available Objectives: Pulmonary embolism (PE is seven times more common in cancer patients than non-cancer patients. Since the existing clinical prediction rules (CPRs were validated predominantly in a non-cancer population, we decided to look at the utility of arterial blood gas (ABG analysis and D-dimer in predicting PE in cancer patients. Methods: Electronic medical records were reviewed between December 2005 and November 2010. A total of 177 computed tomography pulmonary angiograms (CTPAs were performed. We selected 104 individuals based on completeness of laboratory and clinical data. Patients were divided into two groups, CTPA positive (patients with PE and CTPA negative (PE excluded. Wells score, Geneva score, and modified Geneva score were calculated for each patient. Primary outcomes of interest were the sensitivities, specificities, positive, and negative predictive values for all three CPRs. Results: Of the total of 104 individuals who had CTPAs, 33 (31.7% were positive for PE and 71 (68.3% were negative. There was no difference in basic demographics between the two groups. Laboratory parameters were compared and partial pressure of oxygen was significantly lower in patients with PE (68.1 mmHg vs. 71 mmHg, p = 0.030. Clinical prediction rules showed good sensitivities (88−100% and negative predictive values (93−100%. An alveolar-arterial (A-a gradient > 20 had 100% sensitivity and negative predictive values. Conclusions: CPRs and a low A-a gradient were useful in excluding PE in cancer patients. There is a need for prospective trials to validate these results.

  2. Usefulness of Clinical Prediction Rules, D-dimer, and Arterial Blood Gas Analysis to Predict Pulmonary Embolism in Cancer Patients

    Science.gov (United States)

    Karamat, Asifa; Awan, Shazia; Hussain, Muhammad Ghazanfar; Al Hameed, Fahad; Butt, Faheem; Wahla, Ali Saeed

    2017-01-01

    Objectives Pulmonary embolism (PE) is seven times more common in cancer patients than non-cancer patients. Since the existing clinical prediction rules (CPRs) were validated predominantly in a non-cancer population, we decided to look at the utility of arterial blood gas (ABG) analysis and D-dimer in predicting PE in cancer patients. Methods Electronic medical records were reviewed between December 2005 and November 2010. A total of 177 computed tomography pulmonary angiograms (CTPAs) were performed. We selected 104 individuals based on completeness of laboratory and clinical data. Patients were divided into two groups, CTPA positive (patients with PE) and CTPA negative (PE excluded). Wells score, Geneva score, and modified Geneva score were calculated for each patient. Primary outcomes of interest were the sensitivities, specificities, positive, and negative predictive values for all three CPRs. Results Of the total of 104 individuals who had CTPAs, 33 (31.7%) were positive for PE and 71 (68.3%) were negative. There was no difference in basic demographics between the two groups. Laboratory parameters were compared and partial pressure of oxygen was significantly lower in patients with PE (68.1 mmHg vs. 71 mmHg, p = 0.030). Clinical prediction rules showed good sensitivities (88−100%) and negative predictive values (93−100%). An alveolar-arterial (A-a) gradient > 20 had 100% sensitivity and negative predictive values. Conclusions CPRs and a low A-a gradient were useful in excluding PE in cancer patients. There is a need for prospective trials to validate these results. PMID:28439386

  3. The autoantibody profile and its association with clinical manifestations in Malay SLE patients.

    Science.gov (United States)

    Maraina, C H Che; Kamaliah, M D; Ishak, M

    2004-03-01

    A cross sectional study was conducted to determine the auto-antibody profile of Malay SLE patients in Kelantan, North East Malaysia and to correlate them with clinical presentations. Eighty-two Malay SLE patients who fulfilled the ARA criteria underwent the following tests: ANA, anti-dsDNA antibody, anti-ENA antibody and RF. The results revealed that ANA was positive in 91.5% of the patients, anti-dsDNA antibody in 53.7%, however, anti-ENA antibodies were positive in only 9.8% of the cases at the time of the study and none had a positive RF. The profile of autoantibodies was similar to other studies except for a lower incidence of anti-ENA antibodies. Sixty three percent of patients had lupus nephritis. The pattern of clinical presentations were noted to be more similar to those found among Chinese and Indian SLE populations than compared to the Caucasians. There was a significant association between anti-dsDNA antibody and lupus nephritis and between anti-ENA antibody and thrombocytopenia.

  4. A Clinical and Biomarker Scoring System to Predict the Presence of Obstructive Coronary Artery Disease

    NARCIS (Netherlands)

    Ibrahim, N.E.; Januzzi, J.L., Jr.; Magaret, C.A.; Gaggin, H.K.; Rhyne, R.F.; Gandhi, P.U.; Kelly, N.; Simon, M.L.; Motiwala, S.R.; Belcher, A.M.; Kimmenade, R.R. van

    2017-01-01

    BACKGROUND: Noninvasive models to predict the presence of coronary artery disease (CAD) may help reduce the societal burden of CAD. OBJECTIVES: From a prospective registry of patients referred for coronary angiography, the goal of this study was to develop a clinical and biomarker score to predict

  5. [Usefulness of clinical prediction rules for ruling out deep vein thrombosis in a hospital emergency department].

    Science.gov (United States)

    Rosa-Jiménez, Francisco; Rosa-Jiménez, Ascensión; Lozano-Rodríguez, Aquiles; Santoro-Martínez, María Del Carmen; Duro-López, María Del Carmen; Carreras-Álvarez de Cienfuegos, Amelia

    2015-01-01

    To compare the efficacy of the most familiar clinical prediction rules in combination with D-dimer testing to rule out a diagnosis of deep vein thrombosis (DVT) in a hospital emergency department. Retrospective cross-sectional analysis of the case records of all patients attending a hospital emergency department with suspected lower-limb DVT between 1998 and 2002. Ten clinical prediction scores were calculated and D-dimer levels were available for all patients. The gold standard was ultrasound diagnosis of DVT by an independent radiologist who was blinded to clinical records. For each prediction rule, we analyzed the effectiveness of the prediction strategy defined by "low clinical probability and negative D-dimer level" against the ultrasound diagnosis. A total of 861 case records were reviewed and 577 cases were selected; the mean (SD) age was 66.7 (14.2) years. DVT was diagnosed in 145 patients (25.1%). Only the Wells clinical prediction rule and 4 other models had a false negative rate under 2%. The Wells criteria and the score published by Johanning and colleagues identified higher percentages of cases (15.6% and 11.6%, respectively). This study shows that several clinical prediction rules can be safely used in the emergency department, although none of them have proven more effective than the Wells criteria.

  6. Profile of patients treated with omalizumab in routine clinical practice in Spain.

    Science.gov (United States)

    Ancochea, J; Chivato, T; Casan, P; Picado, C; Herráez, L; Casafont, J

    2014-01-01

    Omalizumab is indicated in patients with severe allergic asthma not controlled by high-dose inhaled glucocorticoids and long-acting beta-agonists. Few data are available on the profile of patients treated with this drug in routine clinical practice in Spain. To describe the profile of patients with severe allergic asthma treated with omalizumab and the course of the disease after a period of treatment. Retrospective, multicentre study, recording the data on patients of either sex and ≥12 years with uncontrolled severe allergic asthma, previously treated with omalizumab. Data were evaluated in relation to pulmonary function, symptoms, quality of life, and concomitant anti-asthma treatment before the prescription of omalizumab and at the time of the study visit. 214 patients were evaluable (mean age=48.2±17.7 years; mean age at the time of diagnosis=26.6±16.5 years). 90.7% had experienced exacerbations the year before receiving omalizumab, and the mean total IgE level was 273±205.4IU/ml. The mean monthly dose was 380.5±185.4mg. Compared with the baseline situation, differences were observed after treatment with omalizumab in mean FEV1 (62.7±15.9% vs. 70.8±18.7%), in the proportion of patients requiring oral corticosteroids (47.7% vs. 14.0%), and in the ACQ and AQLQ scores. 32.7% of the patients received doses not recommended by the Summary of Product Characteristics (SPC). Profile of asthmatic patients treated with omalizumab predominantly corresponds to uncontrolled severe asthma cases, in accordance with SPC's indications. The results of the study suggest a favourable clinical course similar to that observed in other studies. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  7. Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome

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    Gustavo A.Rosa Maciel

    2014-03-01

    Full Text Available OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1 polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

  8. CLINICAL PROFILE AND COMMON CAUSES OF HAEMOLYTIC ANAEMIA IN A TERTIARY CARE HOSPITAL, NORTHERN KERALA

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    Jog Antony

    2016-09-01

    Full Text Available BACKGROUND Haemolytic anaemia is a well-recognised clinical problem. This study looks into the clinical profile of haemolytic anaemia and also attempts to find out the common underlying causative disease. It also tries to group the patients according to the clinical manifestations and underlying causes. MATERIALS AND METHODS This is a hospital-based observational study conducted in a tertiary care centre in Northern Kerala. Forty-four adult patients with clinical manifestations and laboratory evidence of haemolytic anaemia were identified and studied for a period of one year. RESULTS Maximum number of cases were seen in the age group of 20-40 years. The overall male-female ratio was 1.1:1. The most common presenting symptoms were features of anaemia like breathlessness, easy fatigability, headache and tiredness. Family history of anaemia was present in 34.1%. The most common signs observed were pallor and jaundice. The most common causes were autoimmune haemolytic anaemia and sickle cell anaemia. CONCLUSION Haemolytic anaemia mostly affects individuals in their 3rd and 4th decade. There is no significant difference in gender distribution of haemolytic anaemia. Haemolytic anaemia most commonly presents with symptoms of anaemia and jaundice. Commonest causes of haemolytic anaemia are autoimmune haemolytic anaemia and sickle cell anaemia.

  9. Establishment of a clinical pathway for home enteral nutrition prescription in Murcia. Profile and sample characteristics

    Science.gov (United States)

    Ferrer Gómez, Mercedes; Sánchez Romera, Juan Francisco; García Zafra, María Victoria; Cuenca Sánchez, José Ramón; Hernández Cascales, Ana Belén; Aranda García, Ana; Rausell Rausell, Víctor José; Hernández Martínez, Antonio Miguel

    2017-06-05

    Introduction: Before 2010, prescribed home enteral nutrition (HEN) in Murcia was characterized by the great variability of the receptor patients, in addition to a higher use compared with other geographical areas. Objectives: Developing and describing a clinical pathway for attending candidates for HEN, and analyzing their profi le and prescription characteristics. Methods: Establishment of a clinical pathway for HEN prescription. Bidirectional observational study of the samples of HEN in a specific area (Health Area I of the Region of Murcia) during 2010 (HEN1) and 2013-14 (HEN2). Results: An official management statement was established, generalizing the clinical pathway for the rest of the regional areas (Instruction no. 4/2012 of July 12 th). Although most prevalent diseases in both samples were neurological, followed, with a wide spread, by oncological and digestive cases, there was a signifi cant difference regarding distribution. The HEN1 sample showed a great number of no candidate patients according to the management statement. In both samples, the most prevalent route of administration was oral, but with a trend reversal to feeding tube and gastrostomy in HEN2, where the specifi c formulas were also reduced. Conclusions: The profile of HEN, before and after the deployment of the clinical pathway, changes signifi cantly concerning the main disease, the route of administration and the formula. It has been proved that there is a need for controlling HEN for an appropriate prescription.

  10. Blood antioxidant profile and lipid peroxides in dairy cows with clinical mastitis

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    Rajesh Rathore

    2013-10-01

    Full Text Available Aim: To evaluate blood antioxidant profile and lipid peroxides in dairy cows with clinical mastitis. Materials and Methods: Twelve cases of clinical mastitis in cross-bred cows were selected based on physical examination of udder and milk, California Mastitis Test (CMT, Somatic Cell Count (SCC and confirmation by bacteriological examination of milk and requisite biochemical tests. Twelve lactating cows showing negative CMT reaction and SCC <2x105 cells/ml were considered as healthy control. Antioxidant parameters measured in blood were superoxide dismutase (SOD, catalase activities and reduced glutathione (GSH concentration. Erythrocytic lipid peroxidation (LPO was measured in terms of malondialdehyde (MDA production. Results: Significant (P<0.05 decrease in blood SOD and catalase activities, GSH concentration and an increase in erythrocytic lipid peroxides was observed in cows with clinical mastitis. Conclusion: It is concluded that there is a compromise in antioxidant defense of the body in dairy cows with clinical mastitis resulting in oxidative damage, therefore, necessitate the use of antioxidants and other protective compounds along with conventional therapy for mastitis control. [Vet World 2013; 6(5.000: 271-273

  11. A Gene Expression Profile of BRCAness that Predicts for Responsiveness to Platinum and PARP Inhibitors

    Science.gov (United States)

    2013-08-01

    will profile tumors for the 60 genes of the BRCAness profile using the NanoString nCounter Platform. The NanoString nCounter has several advantages...a linear dynamic range of over 500-fold. We have now completed the Nanostring nCounter experiments for these samples and we will proceed with the

  12. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity

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    Elisa Passini

    2017-09-01

    Full Text Available Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC50/Hill coefficient. Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca2+-transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs. Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca2+/late Na+ currents and Na+/Ca2+-exchanger, reduced Na+/K+-pump are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

  13. [Epidemiological profile of patients seen in the pre-anesthetic assessment clinic of a university hospital].

    Science.gov (United States)

    Santos, Monica Loureiro; Novaes, Cristiane de Oliveira; Iglesias, Antonio Carlos

    Assess the demographic and clinical characteristics of surgical patients seen in the Pre-anesthetic Assessment Clinic of the Hospital Universitário Gaffrée e Guinle (APA/HUGG), in order to assist in the pursuit for quality, effectiveness, and resource rationalization of hospital management. Cross-sectional descriptive study with 491 patients undergoing elective surgery, treated at APA/HUGG Clinic from March to December 2014. The following variables were assessed: sex, age, BMI, smoking status, associated diseases, classification of MET's and ASA, presence of decompensated disease, medical associated appointments interconsultation, specialty and surgical risk, history of prior anesthetic-surgical procedure, and complications. There was a predominance of female (64.8%) and overweight patients (55.9%), aged 18-59 years. The prevalence of associated diseases was high (71.3%), with hypertension pressure prevailing (50.1%). Most patients had clinically compensated morbidity (96.3%) and long-term use of medication (77.4%). Regarding the surgical characteristics, the most frequent specialty was general and medium risk surgeries. The analysis of the characteristics by age showed that the elderly have more associated diseases and long-term use of medication, in addition to predominance of ASA II-III. The epidemiological profile of surgical patients seen at the APA/HUGG was female, age 18-59 years, overweight, with associated diseases, long-term use of medication, without clinical decompensation, ASA II and MET's ≥4. Knowledge of the clinical characteristics of surgical patients is critical to schedule the perioperative care, allowing the improvement of quality and safety in anesthesia and surgery. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  14. Epidemiological profile of patients seen in the pre-anesthetic assessment clinic of a university hospital

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    Monica Loureiro Santos

    Full Text Available Abstract Objective Assess the demographic and clinical characteristics of surgical patients seen in the Pre-anesthetic Assessment Clinic of the Hospital Universitário Gaffrée e Guinle (APA/HUGG, in order to assist in the pursuit for quality, effectiveness, and resource rationalization of hospital management. Method Cross-sectional descriptive study with 491 patients undergoing elective surgery, treated at APA/HUGG Clinic from March to December 2014. The following variables were assessed: sex, age, BMI, smoking status, associated diseases, classification of MET's and ASA, presence of decompensated disease, medical associated appointments interconsultation, specialty and surgical risk, history of prior anesthetic-surgical procedure, and complications. Results There was a predominance of female (64.8% and overweight patients (55.9%, aged 18-59 years. The prevalence of associated diseases was high (71.3%, with hypertension pressure prevailing (50.1%. Most patients had clinically compensated morbidity (96.3% and long-term use of medication (77.4%. Regarding the surgical characteristics, the most frequent specialty was general and medium risk surgeries. The analysis of the characteristics by age showed that the elderly have more associated diseases and long-term use of medication, in addition to predominance of ASA II-III. Conclusion The epidemiological profile of surgical patients seen at the APA/HUGG was female, age 18-59 years, overweight, with associated diseases, long-term use of medication, without clinical decompensation, ASA II and MET's ≥4. Knowledge of the clinical characteristics of surgical patients is critical to schedule the perioperative care, allowing the improvement of quality and safety in anesthesia and surgery.

  15. Patient profiles and clinical utility of mepolizumab in severe eosinophilic asthma

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    Haldar P

    2017-06-01

    Full Text Available Pranabashis Haldar Respiratory Biomedical Research Unit, Glenfield Hospital, University of Leicester, Leicester, UK Abstract: Mepolizumab (Nucala® is an effective and specific anti-eosinophil molecular therapy that has recently been approved as add-on therapy for the management of severe eosinophilic asthma by the US Food and Drug Administration (FDA, European Medicines Agency (EMA; European Union and more recently National Institute for Health and Care Excellence (NICE; UK. It is one of several molecular therapies in development for this indication and is illustrative of the strategic trajectory for pharmaceutical drug development taken over the past decade in several disease areas. Molecular therapies offer the prospect of improved specificity and effectiveness of biological effect. However, this necessitates a clear understanding of the underlying mechanistic pathways underpinning pathological processes, to inform drug development that yields novel more efficacious treatment options with a better clinical profile than existing agents. For the first time, utilization of molecular therapies in clinical trials is providing a novel in vivo model to characterize the association between specific pathways and clinical disease expression. It is increasingly recognized that asthma exhibits both clinical and pathological heterogeneity. It follows that a one-size-fits-all approach will not be appropriate and cost-effectiveness may only be achieved by identifying responder subgroups. This so-called personalized approach to therapy is being supported by the parallel development of companion biomarkers for clinical application. In this review, the author summarizes the clinical studies, their interpretation and the lessons learnt with mepolizumab that have informed our understanding of the approach to personalized molecular therapy in asthma. Keywords: IL-5, Nucala, exacerbations 

  16. Molecular identification and antifungal susceptibility profile of Aspergillus flavus isolates recovered from clinical specimens in Kuwait

    Science.gov (United States)

    2013-01-01

    Background Within the genus Aspergillus, A. flavus is the second most important species of clinical significance. It is predominantly associated with infections involving sinuses, eye and skin, mostly in geographic regions with hot and arid climate, including the Middle East. Recent reports on emergence of resistance to triazoles among Aspergillus spp. is a cause of concern for treatment of patients with invasive aspergillosis. In this study we present data on genetic characterization and antifungal susceptibility profile of clinical and environmental isolates of A. flavus. Methods Ninety-nine Aspergillus section Flavi isolates, originating from clinical (n=92) and environmental (n=7) sources, initially identified by morphological characteristics, were analyzed by partial sequencing of β-tubulin and calmodulin gene fragments and their susceptibilities to six antifungal agents was determined by Etest on RPMI1640 and Muller-Hinton agar media. Etest minimum inhibitory concentrations (MICs) of amphotericin B and voriconazole were also compared with zone of inhibition diameters obtained by disc diffusion test on RPMI agar medium. Results The identity of all clinical and environmental isolates was confirmed as A. flavus species by combined analysis of β-tubulin and calmodulin genes. The mean MIC90 (μg/ml) values on RPMI medium for amphotericin B, voriconazole, posaconazole, anidulafungin, micafungin and caspofungin were 3, 0.25, 0.25, 0.002, 0.002 and 0.032, respectively. No environmental isolate exhibited MIC value of >2 μg/ml for amphotericin B. For clinical isolates, the zone of inhibition diameters for amphotericin B and voriconazole ranged from 7–16 mm and 24–34 mm, respectively. Linear regression analysis between Etest MIC values and disk diffusion diameters revealed a significant inverse correlation with amphotericin B (p Triazoles and echinocandins showed very good in vitro activity against the A. flavus, however, 10% clinical isolates showed MICs of >2

  17. Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia.

    Science.gov (United States)

    Maasberg, Sebastian; Knappe-Drzikova, Barbora; Vonderbeck, Dorothée; Jann, Henning; Weylandt, Karsten H; Grieser, Christian; Pascher, Andreas; Schefold, Jörg C; Pavel, Marianne; Wiedenmann, Bertram; Sturm, Andreas; Pape, Ulrich-Frank

    2017-01-01

    Malnutrition is a common problem in oncological diseases, influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet been studied systematically in neuroendocrine neoplasms (NEN), which, due to their growing prevalence and additional therapeutic options, provide an increasing clinical challenge to diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches, and to analyse the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. When applying malnutrition screening scores, 21-25% of the NEN patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, by determination of serum surrogate parameters such as albumin as well as by bioelectrical impedance analysis (BIA), particularly phase angle α. The length of hospital stay was significantly longer in malnourished NEN patients, while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk of malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3 NEC). Malnutrition is therefore an underrecognized problem in NEN patients which should systematically be diagnosed by widely available standard methods such as Nutritional Risk Screening (NRS), serum albumin assessment and BIA, and treated to improve both short- and long-term outcomes. © 2015 S. Karger AG, Basel.

  18. Clinical profile of parkinsonian disorders in the tropics: Experience at Kano, northwestern Nigeria

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    Owolabi Lukman Femi

    2012-01-01

    Full Text Available Background: No data exists on Parkinson′s disease (PD and secondary Parkinsonism in Northwestern Nigeria. This study was designed to create a database, document the clinical profile of PD in Kano, northwestern Nigerian, and compare this to prior observations within and outside Nigeria. Materials and Methods: A database was documented on prospective patients presenting consecutively to the Neurology out-patients clinic of the two tertiary health facilities in Kano northwestern Nigeria over a period of 4 years. Demographic and clinical data at presentation were documented for all patients. Cases were classified as PD or secondary Parkinsonism. The severity at presentation and at last visit was classified using the H and Y scale. Results: Over a period of 4 years, out 1153 a total of 96 patients comprising 74 males and 22 females were enrolled. Eighty (83.3% of them had clinically diagnosed PD while 16 (16.7% had clinical features compatible with secondary Parkinsonism. The mean age at onset of symptoms in the PD patients (mean 58.2 ± 6.72 yrs was more than in secondary Parkinsonism (mean 51.4 ± 10.04 and P = 0.001. There was male preponderance in both idiopathic Parkinsonism (PD (m:f = 3.2:1 and secondary Parkinsonism (m:f = 4.3:1. Out of the patients with secondary Parkinsonism, 10 (62.5% and 5 (31.3% had vascular Parkinsonism and drug-induced Parkinsonism, respectively. Duration of symptoms prior to presentation ranged between 3 months and 16 years. The mean (SD time interval from the onset of motor symptoms to diagnosis of PD was 3.6 ± 3.4 yrs and time interval for men and women (male 3.8 ± 3.7; female 2.8 ± 2.1; P = 0.249. Conclusions : Clinical profile of patients with PD and secondary Parkinsonism in Kano is similar to that from other populations within Nigeria and other developing countries. However, delayed presentation, less frequent family history, lower frequency of Young-onset PD as well as treatment challenges occasioned by

  19. Using a Battery of Tests to Predict Suicide in a Long Term Hospital: A Clinical Analysis.

    Science.gov (United States)

    Smith, Kim

    1982-01-01

    Examined the Wechsler-Bellevue, Rorschah, TAT, and Word-Association tests of forty patients for clinical indications of their suicide potential. On the basis of a blind, psychoanalytically informed clinical interpretation of the protocols, the outcomes of these protocols were successfully predicted for 85 percent of the cases. (Author)

  20. Can clinical evaluation predict return to sport after acute hamstring injuries? : a systematic review

    NARCIS (Netherlands)

    Schut, Lotte; Wangensteen, Arnlaug; Maaskant, Jolanda; Tol, Johannes L.; Bahr, Roald; Moen, Maarten

    2016-01-01

    BACKGROUND: The current literature on the value of clinical evaluation for predicting time to return to sport (RTS) after acute hamstring injuries has not been systematically summarised. OBJECTIVES: The aim of this study was to systematically review the literature on the prognostic value of clinical

  1. Clinical and subclinical endometritis induced alterations in bovine endometrial transcriptome and miRNome profile.

    Science.gov (United States)

    Salilew-Wondim, Dessie; Ibrahim, Sally; Gebremedhn, Samuel; Tesfaye, Dawit; Heppelmann, Maike; Bollwein, Heinrich; Pfarrer, Christiane; Tholen, Ernst; Neuhoff, Christiane; Schellander, Karl; Hoelker, Michael

    2016-03-10

    Clinical and subclinical endometritis are known to affect the fertility of dairy cows by inducing uterine inflammation. We hypothesized that clinical or subclinical endometritis could affect the fertility of cows by disturbing the molecular milieu of the uterine environment. Here we aimed to investigate the endometrial molecular signatures and pathways affected by clinical and subclinical endometritis. For this, Holstein Frisian cows at 42-60 days postpartum were classified as healthy (HE), subclinical endometritis (SE) or clinical endometritis (CE) based on veterinary clinical examination of the animals and histological evaluation the corresponding endometrial biopsies. Endometrial transcriptome and miRNome profile changes and associated molecular pathways induced by subclinical or clinical endometritis were then investigated using GeneChip® Bovine Genome Array and Exiqon microRNA PCR Human Panel arrays, respectively. The results were further validated in vitro using endometrial stromal and epithelial cells challenged with subclinical and clinical doses of lipopolysaccharide (LPS). Transcriptome profile analysis revealed altered expression level of 203 genes in CE compared to HE animals. Of these, 92 genes including PTHLH, INHBA, DAPL1 and SERPINA1 were significantly upregulated, whereas the expression level of 111 genes including MAOB, CXCR4, HSD11B and, BOLA, were significantly downregulated in CE compared to the HE animal group. However, in SE group, the expression patterns of only 28 genes were found to be significantly altered, of which 26 genes including PTHLH, INHBA, DAPL1, MAOB, CXCR4 and TGIF1 were common to the CE group. Gene annotation analysis indicated the immune system processes; G-protein coupled receptor signaling pathway and chemotaxis to be among the affected functions in endometritis animal groups. In addition, miRNA expression analysis indicated the dysregulation of 35 miRNAs including miR-608, miR-526b* and miR-1265 in CE animals and 102 mi

  2. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

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    Maria Liguori

    Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  3. Profile of the Treated Patients at the Implantology Clinic of Integrated Schools of Adamantina (FAI

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    Jean Paulo Rodolfo Ferreira

    2015-05-01

    Full Text Available Objective: The aim of this study was to identify the profile of patients treated at the Implantology clinic of the Integrated Schools of Adamantina-FAI, Adamantina-SP, Brazil, through analysis of medical records, appliance of questionnaire and execution of clinical examination. Material and methods: The sample universe of this study consisted of 96 medical records and 96 patients seen over the 9 years of FAI’s experience in the discipline of Implantology. The results were analyzed in the IBM SPSS StatisticsVersion 19 program and the Fisher’s exact and chi-square tests were also applied. Discussion / Results: It was observed that 53.97 % of the participants have lost their natural teeth due to caries. The type of implant prosthesis most used was the fixed denture (88 %. It is also important to note that almost all of the patients had no loss of implant, and these individuals were mostly aged less than or equal to 49 years for women (73.8 % and greater than or equal to 50 years for men (61.8 %. In relation to the quantity of implant elements, the use of 2 implants or less was the most common rehabilitation for both sexes. Another important observation is that only 15.8 % of the participants have the habit of smoking. Conclusion: Thus, the profile of the treated patient at the Implantology clinic of FAI, is mostly women, healthy, aged less than 49 years old, non-smoking, which rehabilitated 1 or 2 teeth, with almost no incidence of implant lost and who opted for fixed denture supported by the implants.

  4. Clinical and autoantibody profile in systemic sclerosis: baseline characteristics from a West Malaysian cohort.

    Science.gov (United States)

    Sujau, Ibrahim; Ng, Chin Teck; Sthaneshwar, Pavai; Sockalingam, Sargunan; Cheah, Tien Eang; Yahya, Fariz; Jasmin, Raja

    2015-05-01

    To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort. Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay. The association between clinical features and autoantibody profile was evaluated. There were 31, predominantly Chinese (45.2%), subjects. Limited cutaneous disease was the most common subtype (71%). Raynaud's phenomenon was the most commonly observed feature (83.9%). Nine (29%) had esophageal dysmotility symptoms and 23 (74.2%), including all patients with diffuse SSc, had symptoms of gastro-esophageal reflux disease (GERD). Restrictive pattern on pulmonary function test and evidence of lung fibrosis were seen in more than 70% of patients. Echocardiographic evidence of pulmonary arterial hypertension was seen in 58.1%. Telangiectasia, calcinosis, digital ulcers, digital pulp loss or pitting were seen more commonly in the diffuse subtype. The two most prevalent autoantibodies were anti-Scl-70 and anti-Ro-52. The presence of anti-Scl-70 was significantly associated with restrictive lung disease (P = 0.05). Anti-Ro-52 was associated with control subjects with other autoimmune diseases (P = 0.043). The presence of anti-PM-Scl-75 was associated with overlap syndrome (P = 0.032). Patients with anticentromere antibodies were more likely to have vasculitic rash (P = 0.012). In Malaysia, SSc most commonly affects the Chinese. Limited cutaneous is more common than diffuse subtype. Features of CREST (calcinosis, Reynaud disease, esophageal dysmotility, sclerodactyly, telangiectasia) are more commonly observed in the diffuse cutaneous subgroup. Anti-Scl-70 and anti-Ro-52 antibodies are promising biomarkers for pulmonary involvement in SSc. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  5. Clinical and mammographic profile of patients with breast cancer surgically treated

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    Raquel Rodrigues Muradas

    2015-06-01

    Full Text Available Summary Objective: to analyze the epidemiological, clinical and mammographic profile of women with breast cancer who were treated at the mastology clinic of the University Hospital of Santa Maria and who underwent breast surgery between January 2007 and December 2012. Methods: this was a cross-sectional study, approved by the Ethics in Research Committee. A review of the patients' medical records was performed. The data were then exported to a software program for statistical analysis, namely Minitab 14.1. Results: the patients' profile indicated that they were mostly born and raised in Santa Maria (respectively 11.1%, n=16, and 26.3%, n=68. They were about 55.6 years old (SD±12.3, white (90.2%, n=213, had already given birth and breastfed their children, were nonsmokers, but also overweight (average BMI of 27kg/m2. On physical examination of the first medical consultation, these patients, as described in the records: had a palpable mass (81.1%, n=184 measuring over three centimeters, located in the left breast, precisely in the upper outer quadrant (41.4%, n=81. Mammography (39%, n=109 showed that this lump was classified as BIRADS ® 5 (40%, n=81. On histopathological examination, the lump was diagnosed as an invasive ductal cancer (71.1%, n=191. Surgery was generally a radical mastectomy (84.7%, n=236 with axillary dissection (92.5%, n=222. Conclusion: some of the epidemiological, clinical and mammographic features mentioned above resembled those found in the literature reviewed. However, these patients had advanced disease and underwent non conservative surgical procedures.

  6. Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia

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    Edgar Leonardo Martínez-Salazar

    2014-06-01

    Full Text Available Introduction Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profile and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profiles of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status. Methods Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8% patients infected with Plasmodium falciparum, 311 (36.1% patients infected with Plasmodium vivax and 18 (2.1% patients with mixed infections. Results The most frequently observed changes were low platelet count (PC and high platelet distribution width (PDW, which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/µL was identified in 11% of patients. Patients with complications had lower PC and plateletcrit (PT and higher PDW values. A higher risk of thrombocytopenia was identified in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction, renal impairment and severe hypoglycemia. The presence of thrombocytopenia (<150,000 platelets/µL was associated with a higher probability of liver dysfunction. Conclusions Young age, longer duration of illness and higher parasitemia are associated with severe thrombocytopenia. Our study showed that thrombocytopenia is related to malaria complications, especially liver dysfunction. High PDW in patients with severe malaria may explain the mechanisms of thrombocytopenia that is common in this group of patients.

  7. Multigene expression profile for predicting efficacy of cisplatin and vinorelbine in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Buhl, I. K.; Christensen, I. J.; Santoni-Rugiu, E.

    2016-01-01

    Background: There is a need for biomarkers to predict efficacy of adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Presented is a combined cisplatin and vinorelbine marker from a previously validated model system [1] tested in two cohorts. Methods: The profiles consist...... of correlated in vitro cytotoxicity of cisplatin and vinorelbine and mRNA expressions. Then each profile is correlated to mRNA expression of 3500 tumors. The cohorts are 1) a publically available dataset with 133 completely resected stage Ib-II NSCLC patients, 71 of whom received adjuvant cisplatin...... and vinorelbine (ACT) and 62 patients who had no adjuvant treatment (OBS) [2] and 2) 95 stage Ib-IIIb completely resected NSCLC patients who all received adjuvant cisplatin and vinorelbine [3]. Endpoint is cancer specific survival. Results: The combined cisplatin and vinorelbine profiles scored as a continuous...

  8. Molecular stratification of metastatic melanoma using gene expression profiling: Prediction of survival outcome and benefit from molecular targeted therapy.

    Science.gov (United States)

    Cirenajwis, Helena; Ekedahl, Henrik; Lauss, Martin; Harbst, Katja; Carneiro, Ana; Enoksson, Jens; Rosengren, Frida; Werner-Hartman, Linda; Törngren, Therese; Kvist, Anders; Fredlund, Erik; Bendahl, Pär-Ola; Jirström, Karin; Lundgren, Lotta; Howlin, Jillian; Borg, Åke; Gruvberger-Saal, Sofia K; Saal, Lao H; Nielsen, Kari; Ringnér, Markus; Tsao, Hensin; Olsson, Håkan; Ingvar, Christian; Staaf, Johan; Jönsson, Göran

    2015-05-20

    Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.

  9. Quiescent and Active Tear Protein Profiles to Predict Vernal Keratoconjunctivitis Reactivation.

    Science.gov (United States)

    Micera, Alessandra; Di Zazzo, Antonio; Esposito, Graziana; Sgrulletta, Roberto; Calder, Virginia L; Bonini, Stefano

    2016-01-01

    Vernal keratoconjunctivitis (VKC) is a chronic recurrent bilateral inflammation of the conjunctiva associated with atopy. Several inflammatory and tissue remodeling factors contribute to VKC disease. The aim is to provide a chip-based protein analysis in tears from patients suffering from quiescent or active VKC. This study cohort included 16 consecutive patients with VKC and 10 controls. Participants were subjected to clinical assessment of ocular surface and tear sampling. Total protein quantification, total protein sketch, and protein array (sixty protein candidates) were evaluated. An overall increased Fluorescent Intensity expression was observed in VKC arrays. Particularly, IL1β, IL15, IL21, Eotaxin2, TACE, MIP1α, MIP3α, NCAM1, ICAM2, βNGF, NT4, BDNF, βFGF, SCF, MMP1, and MMP2 were increased in quiescent VKC. Of those candidates, only IL1β, IL15, IL21, βNGF, SCF, MMP2, Eotaxin2, TACE, MIP1α, MIP3α, NCAM1, and ICAM2 were increased in both active and quiescent VKC. Finally, NT4, βFGF, and MMP1 were highly increased in active VKC. A distinct "protein tear-print" characterizes VKC activity, confirming some previously reported factors and highlighting some new candidates common to quiescent and active states. Those candidates expressed in quiescent VKC might be considered as predictive indicators of VKC reactivation and/or exacerbation out-of-season.

  10. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    Directory of Open Access Journals (Sweden)

    Ji Soo Choi

    Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

  11. Cathode design investigation based on iterative correction of predicted profile errors in electrochemical machining of compressor blades

    Directory of Open Access Journals (Sweden)

    Zhu Dong

    2016-08-01

    Full Text Available Electrochemical machining (ECM is an effective and economical manufacturing method for machining hard-to-cut metal materials that are often used in the aerospace field. Cathode design is very complicated in ECM and is a core problem influencing machining accuracy, especially for complex profiles such as compressor blades in aero engines. A new cathode design method based on iterative correction of predicted profile errors in blade ECM is proposed in this paper. A mathematical model is first built according to the ECM shaping law, and a simulation is then carried out using ANSYS software. A dynamic forming process is obtained and machining gap distributions at different stages are analyzed. Additionally, the simulation deviation between the prediction profile and model is improved by the new method through correcting the initial cathode profile. Furthermore, validation experiments are conducted using cathodes designed before and after the simulation correction. Machining accuracy for the optimal cathode is improved markedly compared with that for the initial cathode. The experimental results illustrate the suitability of the new method and that it can also be applied to other complex engine components such as diffusers.

  12. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer.

    Science.gov (United States)

    Kim, Nam Kyu; Hur, Hyuk

    2015-11-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment.

  13. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech.

    Science.gov (United States)

    Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects.

  14. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech

    Directory of Open Access Journals (Sweden)

    Jennifer L. Whitwell

    2016-01-01

    Full Text Available Beta-amyloid (Aβ deposition can be observed in primary progressive aphasia (PPA and progressive apraxia of speech (PAOS. While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified and PAOS (n = 42 subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+ status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+ status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+ status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified

  15. Relating multi-sequence longitudinal intensity profiles and clinical covariates in incident multiple sclerosis lesions

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Sweeney

    2016-01-01

    Full Text Available The formation of multiple sclerosis (MS lesions is a complex process involving inflammation, tissue damage, and tissue repair — all of which are visible on structural magnetic resonance imaging (MRI and potentially modifiable by pharmacological therapy. In this paper, we introduce two statistical models for relating voxel-level, longitudinal, multi-sequence structural MRI intensities within MS lesions to clinical information and therapeutic interventions: (1 a principal component analysis (PCA and regression model and (2 function-on-scalar regression models. To do so, we first characterize the post-lesion incidence repair process on longitudinal, multi-sequence structural MRI from 34 MS patients as voxel-level intensity profiles. For the PCA regression model, we perform PCA on the intensity profiles to develop a voxel-level biomarker for identifying slow and persistent, long-term intensity changes within lesion tissue voxels. The proposed biomarker's ability to identify such effects is validated by two experienced clinicians (a neuroradiologist and a neurologist. On a scale of 1 to 4, with 4 being the highest quality, the neuroradiologist gave the score on the first PC a median quality rating of 4 (95% CI: [4,4], and the neurologist gave the score a median rating of 3 (95% CI: [3,3]. We then relate the biomarker to the clinical information in a mixed model framework. Treatment with disease-modifying therapies (p < 0.01, steroids (p < 0.01, and being closer to the boundary of abnormal signal intensity (p < 0.01 are all associated with return of a voxel to an intensity value closer to that of normal-appearing tissue. The function-on-scalar regression model allows for assessment of the post-incidence time points at which the covariates are associated with the profiles. In the function-on-scalar regression, both age and distance to the boundary were found to have a statistically significant association with the lesion intensities at some

  16. Through-Thickness Residual Stress Profiles in Austenitic Stainless Steel Welds: A Combined Experimental and Prediction Study

    Science.gov (United States)

    Mathew, J.; Moat, R. J.; Paddea, S.; Francis, J. A.; Fitzpatrick, M. E.; Bouchard, P. J.

    2017-10-01

    Economic and safe management of nuclear plant components relies on accurate prediction of welding-induced residual stresses. In this study, the distribution of residual stress through the thickness of austenitic stainless steel welds has been measured using neutron diffraction and the contour method. The measured data are used to validate residual stress profiles predicted by an artificial neural network approach (ANN) as a function of welding heat input and geometry. Maximum tensile stresses with magnitude close to the yield strength of the material were observed near the weld cap in both axial and hoop direction of the welds. Significant scatter of more than 200 MPa was found within the residual stress measurements at the weld center line and are associated with the geometry and welding conditions of individual weld passes. The ANN prediction is developed in an attempt to effectively quantify this phenomenon of `innate scatter' and to learn the non-linear patterns in the weld residual stress profiles. Furthermore, the efficacy of the ANN method for defining through-thickness residual stress profiles in welds for application in structural integrity assessments is evaluated.

  17. Through-Thickness Residual Stress Profiles in Austenitic Stainless Steel Welds: A Combined Experimental and Prediction Study

    Science.gov (United States)

    Mathew, J.; Moat, R. J.; Paddea, S.; Francis, J. A.; Fitzpatrick, M. E.; Bouchard, P. J.

    2017-12-01

    Economic and safe management of nuclear plant components relies on accurate prediction of welding-induced residual stresses. In this study, the distribution of residual stress through the thickness of austenitic stainless steel welds has been measured using neutron diffraction and the contour method. The measured data are used to validate residual stress profiles predicted by an artificial neural network approach (ANN) as a function of welding heat input and geometry. Maximum tensile stresses with magnitude close to the yield strength of the material were observed near the weld cap in both axial and hoop direction of the welds. Significant scatter of more than 200 MPa was found within the residual stress measurements at the weld center line and are associated with the geometry and welding conditions of individual weld passes. The ANN prediction is developed in an attempt to effectively quantify this phenomenon of `innate scatter' and to learn the non-linear patterns in the weld residual stress profiles. Furthermore, the efficacy of the ANN method for defining through-thickness residual stress profiles in welds for application in structural integrity assessments is evaluated.

  18. Sociodemographic and clinical profile of children with congenital heart disease assisted at a hospital institution

    Directory of Open Access Journals (Sweden)

    Mirna Albuquerque Frota

    2014-06-01

    Full Text Available Objective: To characterize the sociodemographic and clinical profile of children with congenital heart disease assisted at a hospital institution. Methods: A descriptive, crosssectional study conducted in the pediatric cardiology outpatient clinic of a hospital in Fortaleza, CE, Brazil, in the period from March to August 2012. It comprised a nonrandom convenience sample of 80 parents of children with heart disease aged 5 to 12 years. Information was obtained from primary data of medical records and through questionnaires covering the parent’s sociodemographic characteristics, family data and the children’s clinical aspects. Results: Regarding socioeconomic data, 77 (96.2% caregivers were female, 50 (62.5% were married or in a stable relationship, 39 (48.7% had 10-12 years of formal education, and 69 (82.6% reported a household income between 1 and 2 minimum wages. In the sample of children studied, 43 (53.8% were female. The median age of the children was 8.4 years, ranging from 5-13 years. As to the age at the heart disease diagnosis, 44 (55% occurred under the age of 6 months, regardless of the type of cardiopathy. It was detected that 19 (23.75% were related to the disease. Conclusion: Children’s caregivers were predominantly their mothers, with low income and satisfactory schooling. Early diagnosis was predominant, mainly among the children with cyanotic cardiopathy. doi:10.5020/18061230.2014.p239

  19. Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases.

    Science.gov (United States)

    Siller-Matula, Jolanta M; Krumphuber, Julia; Jilma, Bernd

    2010-02-01

    Platelet inhibitors are the mainstay treatment for patients with vascular diseases. The current 'gold standard' antiplatelet agent clopidogrel has several pharmacological and clinical limitations that have prompted the search for more effective platelet antagonists. The candidates include various blockers of the purinergic P2Y12 receptor such as prasugrel, an oral irreversible thienopyridine; two adenosine triphosphate analogues that bind reversibly to the P2Y12 receptor: ticagrelor (oral) and cangrelor (intravenous); elinogrel, a direct-acting reversible P2Y12 receptor inhibitor (the only antiplatelet compound that can be administered both intravenously and orally); BX 667, an orally active and reversible small-molecule P2Y12 receptor antagonist; SCH 530348, SCH 205831, SCH 602539 and E5555, highly selective and orally active antagonists on the protease-activated receptor 1. A number of drugs also hit new targets: terutroban, an oral, selective and specific inhibitor of the thromboxane receptor; ARC1779, a second-generation, nuclease resistant aptamer which inhibits von Willebrand factor-dependent platelet aggregation; ALX-0081, a bivalent humanized nanobody targeting the GPIb binding site of von Willebrand factor and AJW200, an IgG4 monoclonal antibody of von Willebrand factor. The pharmacology and clinical profiles of new platelet antagonists indicate that they provide more consistent, more rapid and more potent platelet inhibition than agents currently used. Whether these potential advantages will translate into clinical advantages will require additional comparisons in properly powered, randomized, controlled trials.

  20. A profile of Australian football injuries presenting to sports medicine clinics.

    Science.gov (United States)

    Gabbe, B; Finch, C

    2001-12-01

    Most of the published data describing Australian football injuries is from hospital emergency departments and elite injury surveillance studies. There is a lack of good information about injuries to players at the lower levels of participation and those not severe enough to warrant hospital treatment. This study describes the profile of Australian football injuries that present to sports medicine clinics for treatment. New sports injury cases, presenting to five metropolitan Melbourne sports medicine clinics during a 12 month period in 1996-1997, were recorded through the Sports Medicine Injury Surveillance project. Both the patient and treating health professional provided personal and injury details. Australian football accounted for 29% of the 6479 recorded injury cases. The majority of injured players were male (99%) and from adult, community leagues (78%); the mean age was 23 years. Competition accounted for 78% of injuries and 72% of injured players presented for treatment to a sports physician/medical practitioner. Body contact accounted for half of all injuries and the most common injuries were medial ligament sprains of the knee (7%), lateral ligament sprains of the ankle (6%) and anterior cruciate ligament injuries (4%). In conclusion, sports medicine clinics treat a wide variety of football injuries and appear to be a good source of data about injuries to non-elite participants.

  1. Quality controls in cellular immunotherapies: rapid assessment of clinical grade dendritic cells by gene expression profiling.

    Science.gov (United States)

    Castiello, Luciano; Sabatino, Marianna; Zhao, Yingdong; Tumaini, Barbara; Ren, Jiaqiang; Ping, Jin; Wang, Ena; Wood, Lauren V; Marincola, Francesco M; Puri, Raj K; Stroncek, David F

    2013-02-01

    Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers.

  2. Study of clinical profile and management of patients with pulmonary embolism – Single center study

    Science.gov (United States)

    Calwin Davidsingh, S.; Srinivasan, Narayanan; Balaji, P.; Kalaichelvan, U.; Mullasari, Ajit Sankaradas

    2014-01-01

    Objective To study the clinical profile, diagnostic methods and management in patients with symptomatic pulmonary embolism (PE). Methods Retrospective assessment of clinical features and management of patients presenting with symptomatic pulmonary embolism from January 2005 to March 2012. Results 35 patients who were newly diagnosed to have pulmonary embolism with a mean age of 52.1 years were included in the study. Dyspnea (91.4%) and syncope (22.8%) were the predominant symptoms. Echocardiography was done in all patients. 30 patients (85.7%) had pulmonary arterial hypertension, 31 patients (88.5%) had evidence of RV dysfunction and 4 patients (16.7%) had evidence of thrombus in PA, RV. Out of 35 patients, 34 patients (97.14%) showed positive d-dimer reports. Among 35 patients, 24 (68.5%) had positive troponin values. V/Q scan was done in 14 patients (40%) and CT pulmonary angiogram (CTPA) was done in 24 patients (68.5%.). Thrombolysis was done is 24 patients (68.5%). All patients received low molecular weight heparin followed by warfarin. Of the 35 patients, 34 (97.1%) were discharged and were under regular follow up for 6 months and one patient died during the hospital stay. Conclusion Pulmonary embolism is a common problem and can be easily diagnosed provided it is clinically suspected. Early diagnosis and aggressive management is the key to successful outcome. PMID:24814115

  3. Demographic and clinical profile of vernal keratoconjunctivitis at a tertiary eye care center in India.

    Science.gov (United States)

    Saboo, Ujwala S; Jain, Manish; Reddy, Jagadesh C; Sangwan, Virender S

    2013-09-01

    To study the demographic and clinical profile of patients with vernal keratoconjunctivitis (VKC) at a tertiary eye care center in India. Retrospective chart analysis of 468 patients of VKC seen from January 2006 to December 2006. Mean age at presentation was 12 years. Majority of the patients had mixed pattern disease (72%). Chronic perennial disease was seen in 36% patients. Personal or family history of allergies was noted in 5% patients. Severe disease based on clinical grading was present in 37% patients. Moderate to severe vision loss was seen in 12% of total population. Persistent disease beyond 20 years of age was found in 12% patients. VKC-related complications such as corneal scarring (11%), shield ulcer (3%), keratoconus (6%), and limbal stem cell deficiency (1.2%) were seen. Treatment-related complications like corticosteroid-induced cataract and glaucoma were seen in 6% and 4% of patients, respectively. Clinical pattern of VKC seen in the tropical climate of India is essentially similar to that seen in other tropical countries. Few distinct features that we noted represent chronic perennial disease, low association with atopy, and higher propensity for disease and treatment-related complications.

  4. Differential clinical profile of candesartan compared to other angiotensin receptor blockers.

    Science.gov (United States)

    Cernes, Relu; Mashavi, Margarita; Zimlichman, Reuven

    2011-01-01

    The advantages of blood pressure (BP) control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1]) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8-32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.

  5. Clinical and autonomic profile of patients with Alzheimer's disease and mixed dementia patients.

    Science.gov (United States)

    Dias, Filipi Leles da Costa; Silva, Rose Mary Ferreira Lisboa da; Moraes, Edgar Nunes de; Caramelli, Paulo

    2013-01-01

    To analyze the clinical and autonomical profile of patients with Alzheimer's disease or mixed dementia (MD). Fifty-four patients with indication for cholinesterase inhibitors use were evaluated through clinical examination, rest electrocardiogram, and spectral analysis of heart rate (HR) variability through digital Holter system recordings. Overall, 61.1% of patients were female and were, on average, 77.1 years of age, 3.3 years of schooling and scored 16.4 points on the Mini Mental State Examination. The gap between symptom onset and diagnosis was 26.2 months. Almost all patients (90.7%) presented at least one clinical comorbidity, and each patient took, on average, 3.7 drugs to control them. Thirty-one patients had some alteration on the electrocardiogram and nine (16.6%) had orthostatic hypotension (OH). The latter was associated with the diagnosis of MD (p=0.001), with lower values of low (LF) and high (HF) frequency components of the spectral analysis in the supine position (p=0.000 and p=0.017, respectively) and with lower values of LF in the orthostatic position (p=0.006). Diagnosis of MD was associated with lower values of LF in both positions (p=0.003 and p=0.007). This sample of patients had frequent comorbidities, which resulted in the prescription of multiple drugs. Signs of autonomic dysfunction resulting in OH were found mainly in those with MD. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  6. Clinical applications of epigenetic markers and epigenetic profiling in myeloid malignancies.

    Science.gov (United States)

    McDevitt, Michael A

    2012-02-01

    Aberrant DNA methylation is frequent in the myeloid malignancies, particularly myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Promoter CpG methylation is correlated with silencing of tumor-suppressor genes (TSGs) in specific pathways that are also targets of mutat