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Sample records for accurate risk stratification

  1. Sudden Cardiac Death Risk Stratification

    PubMed Central

    Deyell, Marc W.; Krahn, Andrew D.; Goldberger, Jeffrey J.

    2015-01-01

    Arrhythmic sudden cardiac death (SCD) may be due to ventricular tachycardia/fibrillation (SCD-VT/VF) or pulseless electrical activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our health care and research resources to tackle this important public health issue. Although our understanding of SCD due to pulseless electrical activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-VT/VF. This review focuses on existing and novel risk stratification tools for SCD-VT/VF. For patients with left ventricular dysfunction and/or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-VT/VF occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized. PMID:26044247

  2. Risk Stratification in Multiple Myeloma.

    PubMed

    Ooi, Melissa Gaik-Ming; de Mel, Sanjay; Chng, Wee Joo

    2016-04-01

    There are many prognostic variables in multiple myeloma and the difficulty is in deciding which is truly significant. The widely used International Staging System (ISS) does not incorporate genetics, age, and other important variables in its risk stratification. Although it has its own limitations, the recently published Revised International Staging System (R-ISS) that was built upon the framework of ISS, is a more comprehensive and predictive tool for multiple myeloma patients and should be henceforth utilised. We will review the current prognostic variables and their significance in this paper. PMID:26883334

  3. Risk Stratification in Differentiated Thyroid Cancer: An Ongoing Process

    PubMed Central

    Omry-Orbach, Gal

    2016-01-01

    Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts postoperatively with histopathologic staging, based on the AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and, if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low, intermediate, or high risk for recurrence. Over the course of time, a response-to-therapy variable is incorporated, and patients essentially undergo continuous risk stratification. Additional tools such as biochemical markers, genetic mutations, and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality

  4. Syncope risk stratification in the ED.

    PubMed

    Dipaola, Franca; Costantino, Giorgio; Solbiati, Monica; Barbic, Franca; Capitanio, Chiara; Tobaldini, Eleonora; Brunetta, Enrico; Zamunér, Antonio Roberto; Furlan, Raffaello

    2014-09-01

    Syncope may be the final common presentation of a number of clinical conditions spanning benign (i.e. neurally-mediated syncope) to life-threatening diseases (i.e. cardiac syncope). Hospitalization rate after a syncopal episode is high. An effective risk stratification is crucial to identify patients at risk of poor prognosis in the short term period to avoid unnecessary hospital admissions. The decision to admit or discharge a syncope patient from the ED is often based on the physician's clinical judgment. In recent years, several prognostic tools (i.e. clinical prediction rules and risk scores) have been developed to provide emergency physicians with accurate guidelines for hospital admission. At present, there are no compelling evidence that prognostic tools perform better than physician's clinical judgment in assessing the short-term outcome of syncope. However, the risk factors characterizing clinical prediction rules and risk scores may be profitably used by emergency doctors in their decision making, specifically whenever a syncope patient has to be discharged from ED or admitted to hospital. Patients with syncope of undetermined etiology, who are characterized by an intermediate-high risk profile after the initial evaluation, should be monitored in the ED. Indeed, data suggest that the 48h following syncope are at the highest risk for major adverse events. A new tool for syncope management is represented by the Syncope Unit in the ED or in an outpatient setting. Syncope Unit may reduce hospitalization and length of hospital stay. However, further studies are needed to clarify whether syncope patients' prognosis can be also improved. PMID:24811585

  5. Risk stratification for sudden cardiac death

    PubMed Central

    Cutler, Michael J; Rosenbaum, David S.

    2009-01-01

    The proportion of cardiovascular deaths attributable to sudden cardiac death (SCD) is on the rise. Herein lies the rationale for developing risk stratification strategies to predict who will benefit from prophylactic ICD implantation. Current guidelines recommend prophylactic ICD therapy in patients with reduced left ventricular ejection fraction (LVEF). However, there are clear limitations in using LVEF alone to decide who should receive an ICD. There is mounting evidence that microvolt-level T wave alternans (TWA) is an important marker of arrhythmic risk. TWA is appealing because it non-invasively probes underlying electrophysiological substrate and has been linked to cellular mechanisms for arrhythmias. This review considers the clinical role of TWA for risk stratification of SCD. PMID:19631909

  6. Is risk stratification ever the same as 'profiling'?

    PubMed

    Braithwaite, R Scott; Stevens, Elizabeth R; Caplan, Arthur

    2016-05-01

    Physicians engage in risk stratification as a normative part of their professional duties. Risk stratification has the potential to be beneficial in many ways, and implicit recognition of this potential benefit underlies its acceptance as a cornerstone of the medical profession. However, risk stratification also has the potential to be harmful. We argue that 'profiling' is a term that corresponds to risk stratification strategies in which there is concern that ethical harms exceed likely or proven benefits. In the case of risk stratification for health goals, this would occur most frequently if benefits were obtained by threats to justice, autonomy or privacy. We discuss implications of the potential overlap between risk stratification and profiling for researchers and for clinicians, and we consider whether there are salient characteristics that make a particular risk stratification algorithm more or less likely to overlap with profiling, such as whether the risk stratification algorithm is based on voluntary versus non-voluntary characteristics, based on causal versus non-causal characteristics, or based on signifiers of historical disadvantage. We also discuss the ethical challenges created when a risk stratification scheme helps all subgroups but some more than others, or when risk stratification harms some subgroups but benefits the aggregate group. PMID:26796335

  7. Risk stratification after myocardial infarction. Clinical overview

    SciTech Connect

    O'Rourke, R.A. )

    1991-09-01

    Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification.

  8. Cardiac PET Perfusion: Prognosis, Risk Stratification, Clinical Management

    PubMed Central

    Dorbala, Sharmila; Di Carli, Marcelo F.

    2014-01-01

    Myocardial perfusion imaging (MPI) with positron emission tomography (PET) has expanded significantly over the past decade. With the wider availability of PET scanners and the routine use of quantitative blood flow imaging, the clinical use of PET MPI is expected to increase further. PET MPI is a powerful tool to identify risk, to quantify risk, and to guide therapy in patients with known or suspected coronary artery disease (CAD). A large body of evidence supports the prognostic value of PET MPI and ejection fraction in intermediate to high risk subjects, in women, in obese individuals and in post coronary artery bypass grafting (CABG) individuals. A normal perfusion study indicates low risk (< 1% annualized rate of cardiac events of cardiac death and non-fatal myocardial infarction), while an abnormal study indicates high risk. With accurate risk stratification, high quality images, and quantitation PET MPI may transform the management of patients with known or suspected CAD. PMID:25234079

  9. Cytogenetic risk stratification in chronic myelomonocytic leukemia

    PubMed Central

    Such, Esperanza; Cervera, José; Costa, Dolors; Solé, Francesc; Vallespí, Teresa; Luño, Elisa; Collado, Rosa; Calasanz, María J.; Hernández-Rivas, Jesús M.; Cigudosa, Juan C.; Nomdedeu, Benet; Mallo, Mar; Carbonell, Felix; Bueno, Javier; Ardanaz, María T.; Ramos, Fernando; Tormo, Mar; Sancho-Tello, Reyes; del Cañizo, Consuelo; Gómez, Valle; Marco, Victor; Xicoy, Blanca; Bonanad, Santiago; Pedro, Carmen; Bernal, Teresa; Sanz, Guillermo F.

    2011-01-01

    Background The prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. Design and Methods We studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia. Results Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis. Conclusions Cytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia. PMID:21109693

  10. Ventricular repolarization measures for arrhythmic risk stratification

    PubMed Central

    Monitillo, Francesco; Leone, Marta; Rizzo, Caterina; Passantino, Andrea; Iacoviello, Massimo

    2016-01-01

    Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave (QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice. PMID:26839657

  11. Role of risk stratification after myocardial infarction.

    PubMed

    Kuriachan, Vikas; Exner, Derek V

    2009-02-01

    Despite advances in medical and surgical therapy for patients with heart disease, sudden cardiac death remains an important public health problem that prematurely ends the lives of more than 300,000 persons each year in North America. Many of these deaths occur in patients with a history of myocardial infarction (MI). Although severe left ventricular (LV) systolic dysfunction is used to identify patients at risk of sudden death after MI, most cardiac arrests occur in those with only mild LV dysfunction. Further, severe LV dysfunction is not a specific indicator for cardiac arrest. Risk stratification, to identify patients most likely to benefit from implantable defibrillator therapy after MI, is an essential area of investigation. Because the development of cardiac arrest is complex and likely requires the confluence of several factors, using a single test to predict the risk of sudden death or to guide implantable defibrillator therapy is unlikely to be successful. Tests that assess cardiac structure, including repolarization, and those that evaluate autonomic modulation and other factors have been developed with the goal of identifying patients at highest risk of cardiac arrest after MI. These tests, particularly in combination, appear to identify patients who may benefit from implantable defibrillator therapy after MI. Ongoing and planned randomized controlled trials will assess whether these tests can be used to guide implantable defibrillator therapy. Until the data from these studies are available, severe LV dysfunction remains the only proven approach to guide implantable defibrillator therapy after MI. PMID:19141257

  12. Accurate cloud-based smart IMT measurement, its validation and stroke risk stratification in carotid ultrasound: A web-based point-of-care tool for multicenter clinical trial.

    PubMed

    Saba, Luca; Banchhor, Sumit K; Suri, Harman S; Londhe, Narendra D; Araki, Tadashi; Ikeda, Nobutaka; Viskovic, Klaudija; Shafique, Shoaib; Laird, John R; Gupta, Ajay; Nicolaides, Andrew; Suri, Jasjit S

    2016-08-01

    This study presents AtheroCloud™ - a novel cloud-based smart carotid intima-media thickness (cIMT) measurement tool using B-mode ultrasound for stroke/cardiovascular risk assessment and its stratification. This is an anytime-anywhere clinical tool for routine screening and multi-center clinical trials. In this pilot study, the physician can upload ultrasound scans in one of the following formats (DICOM, JPEG, BMP, PNG, GIF or TIFF) directly into the proprietary cloud of AtheroPoint from the local server of the physician's office. They can then run the intelligent and automated AtheroCloud™ cIMT measurements in point-of-care settings in less than five seconds per image, while saving the vascular reports in the cloud. We statistically benchmark AtheroCloud™ cIMT readings against sonographer (a registered vascular technologist) readings and manual measurements derived from the tracings of the radiologist. One hundred patients (75 M/25 F, mean age: 68±11 years), IRB approved, Toho University, Japan, consisted of Left/Right common carotid artery (CCA) artery (200 ultrasound scans), (Toshiba, Tokyo, Japan) were collected using a 7.5MHz transducer. The measured cIMTs for L/R carotid were as follows (in mm): (i) AtheroCloud™ (0.87±0.20, 0.77±0.20); (ii) sonographer (0.97±0.26, 0.89±0.29) and (iii) manual (0.90±0.20, 0.79±0.20), respectively. The coefficient of correlation (CC) between sonographer and manual for L/R cIMT was 0.74 (P<0.0001) and 0.65 (P<0.0001), while, between AtheroCloud™ and manual was 0.96 (P<0.0001) and 0.97 (P<0.0001), respectively. We observed that 91.15% of the population in AtheroCloud™ had a mean cIMT error less than 0.11mm compared to sonographer's 68.31%. The area under curve for receiving operating characteristics was 0.99 for AtheroCloud™ against 0.81 for sonographer. Our Framingham Risk Score stratified the population into three bins as follows: 39% in low-risk, 70.66% in medium-risk and 10.66% in high-risk bins

  13. Risk stratification in non-ST elevation acute coronary syndromes: Risk scores, biomarkers and clinical judgment

    PubMed Central

    Corcoran, David; Grant, Patrick; Berry, Colin

    2015-01-01

    Undifferentiated chest pain is one of the most common reasons for emergency department attendance and admission to hospitals. Non-ST elevation acute coronary syndrome (NSTE-ACS) is an important cause of chest pain, and accurate diagnosis and risk stratification in the emergency department must be a clinical priority. In the future, the incidence of NSTE-ACS will rise further as higher sensitivity troponin assays are implemented in clinical practice. In this article, we review contemporary approaches for the diagnosis and risk stratification of NSTE-ACS during emergency care. We consider the limitations of current practices and potential improvements. Clinical guidelines recommend an early invasive strategy in higher risk NSTE-ACS. The Global Registry of Acute Coronary Events (GRACE) risk score is a validated risk stratification tool which has incremental prognostic value for risk stratification compared with clinical assessment or troponin testing alone. In emergency medicine, there has been a limited adoption of the GRACE score in some countries (e.g. United Kingdom), in part related to a delay in obtaining timely blood biochemistry results. Age makes an exponential contribution to the GRACE score, and on an individual patient basis, the risk of younger patients with a flow-limiting culprit coronary artery lesion may be underestimated. The future incorporation of novel cardiac biomarkers into this diagnostic pathway may allow for earlier treatment stratification. The cost-effectiveness of the new diagnostic pathways based on high-sensitivity troponin and copeptin must also be established. Finally, diagnostic tests and risk scores may optimize patient care but they cannot replace patient-focused good clinical judgment. PMID:26753174

  14. Surgical site infection risk factors and risk stratification.

    PubMed

    Florschutz, Anthony V; Fagan, Ryan P; Matar, Wadih Y; Sawyer, Robert G; Berrios-Torres, Sandra I

    2015-04-01

    Preoperative identification of the risk factors for surgical site infection and patient risk stratification are essential for deciding whether surgery is appropriate, educating patients on their individual risk of complications, and managing postoperative expectations. Early identification of these factors is also necessary to help guide both patient medical optimization and perioperative care planning. Several resources are currently available to track and analyze healthcare-associated infections, including the Centers for Disease Control and Prevention's National Healthcare Safety Network. In addition, the Centers for Disease Control and Prevention and the American Academy of Orthopaedic Surgeons are exploring collaborative opportunities for the codevelopment of a hip and/or knee arthroplasty national quality measure for periprosthetic joint infection. PMID:25808971

  15. Risk stratification strategies for cancer-associated thrombosis: an update.

    PubMed

    Khorana, Alok A; McCrae, Keith R

    2014-05-01

    Rates of venous thromboembolism (VTE) vary substantially between cancer patients. Multiple clinical risk factors including primary site of cancer and systemic therapy, and biomarkers including leukocyte and platelet counts and tissue factor are associated with increased risk of VTE. However, risk cannot be reliably predicted based on single risk factors or biomarkers. New American Society of Clinical Guidelines recommend that patients with cancer be assessed for VTE risk at the time of chemotherapy initiation and periodically thereafter. This narrative review provides an update on risk stratification approaches including a validated Risk Score. Potential applications of risk assessment including targeted thromboprophylaxis are outlined. © 2014 Elsevier Ltd. All rights reserved. PMID:24862143

  16. Coronary computed tomography angiography for risk stratification before noncardiac surgery

    PubMed Central

    Fathala, Ahmed

    2016-01-01

    Background: Currently, there are limited available data for coronary computed tomography angiography (CCTA) in the setting of the risk stratification before noncardiac surgery. The main purpose of this study is to investigate the role of CCTA in cardiac risk stratification before noncardiac surgery. Materials and Methods: Ninety-three patients underwent CCTA in the assessment of cardiac risk before noncardiac surgery. Patients with normal or mildly abnormal CCTA (<50% stenosis) underwent surgery without any further testing (Group 1). Patients with abnormal CCTA (17 patients) (more than 50% stenosis) and nondiagnostic CCTA (5%) underwent either stress myocardial perfusion scintigraphy or conventional coronary angiography, Group 2. Results: Group one consists of 71 patients who went for surgery without any further testing. 59 of 71 (83%) patients had no complications in the postoperative period, 9 patients had noncardiac complications, 1 had a cardiac complication (new onset atrial fibrillation), and 2 patients died in the postoperative period due to noncardiac complications. Group 2 comprises 22 (26%) patients, 16 patients had no postoperative complications, 5 patients had noncardiac complications, and one patient developed postoperative acute heart failure. Conclusions: CCTA is diagnostic in up to 95% in the preoperative setting, and it provides a comprehensive cardiac examination in the risk stratification before intermediate and high-risk noncardiac surgery. Therefore, CCTA may be considered as an alternative test for already established imaging techniques for preoperative cardiac risk stratification before noncardiac surgery. PMID:26750671

  17. First review on psoriasis severity risk stratification: An engineering perspective.

    PubMed

    Shrivastava, Vimal K; Londhe, Narendra D; Sonawane, Rajendra S; Suri, Jasjit S

    2015-08-01

    Computer-aided diagnosis (CAD) systems have been used for characterization of several dermatologic diseases in the last few years. Psoriasis is a potentially life-threatening skin disease which affects 125 million people worldwide. The paper presents the first state-of-the-art review of technology solicitation in psoriasis along with its current practices, challenges and assessment techniques. The paper also conducts in-depth examination of the existing literature for all clinical parameters of Psoriasis Area and Severity Index (PASI) i.e., area, erythema, scaliness and thickness. We suggest a role of risk assessment using a decision support system for stratification of psoriasis in large populations. A balanced insight has been presented in all the components of the design, namely: feature extraction, feature selection, disease stratification and overall CAD performance evaluation. We conclude that CAD systems are promising for risk stratification and assessment of psoriasis. PMID:26005793

  18. Risk stratification of prostate cancer in the modern era

    PubMed Central

    Behesnilian, Andrew S.; Reiter, Robert E.

    2015-01-01

    Purpose of Review Novel tools have become available to the practicing urologist in recent years that endeavor to improve on commonly utilized prostate cancer (PCa) risk stratification techniques. In this review, we provide an overview of these modalities in the context of active surveillance. Recent Findings Multiparametric magnetic resonance imaging (MP-MRI) has a rapidly growing body of evidence that suggests it provides the necessary sensitivity and NPV to rule out clinically significant disease. MRI-guided targeted biopsy has the potential to improve detection of clinically significant cancers and for rebiopsy of patients with continued suspicion for PCa. PSA isoforms and Prostate Health Index (PHI) outperform PSA alone and improve risk stratification when combined with established criteria, but need further prospective studies using template and MRI-targeted biopsies. Urinary biomarkers tend to fall short in predicting adverse pathology when used alone, but improve risk-stratification when used in conjunction and with established criteria. Finally, tissue biomarkers and gene assays allow for patient-specific molecular and genetic characterization of cancer phenotype, showing significant promise in predicting adverse pathology and in some cases have already been incorporated into and altered clinical practice. Summary These novel modalities show remarkable promise in improving the risk-stratification of patients with PCa, and as the body of evidence grows will likely become incorporated into major oncologic guidelines and standard urologic practice. Further prospective clinical studies are needed, as well as analysis of cost-effectiveness. PMID:25730325

  19. Cardiovascular risk stratification in familial hypercholesterolaemia.

    PubMed

    Sharifi, Mahtab; Rakhit, Roby D; Humphries, Steve E; Nair, Devaki

    2016-07-01

    Familial hypercholesterolaemia (FH) is a common autosomal-dominant disorder in most European countries. Patients with FH are characterised by a raised level of low-density lipoprotein cholesterol and a high risk of premature coronary heart disease (CHD). Currently there is no consensus regarding the clinical utility to predict future coronary events or testing for the presence of subclinical atherosclerotic disease in asymptomatic patients with FH. Family screening of patients with FH as recommended by the UK National Institute of Health and Care Excellence guideline would result in finding many young individuals with a diagnosis of FH who are clinically asymptomatic. The traditional CHD risk scores, that is, the Framingham score, are insufficient in risk prediction in this group of young individuals. In addition, a better understanding of the genetic aetiology of the FH phenotype and CHD risk in monogenic FH and polygenic hypercholesterolaemia is needed. Non-invasive imaging methods such as carotid intima-media thickness measurement might produce more reliable information in finding high-risk patients with FH. The potential market authorisation of novel therapeutic agents such as PCSK9 monoclonal inhibitors makes it essential to have a better screening programme to prioritise the candidates for treatment with the most severe form of FH and at higher risk of coronary events. The utility of new imaging techniques and new cardiovascular biomarkers remains to be determined in prospective trials. PMID:27126396

  20. Cardiovascular risk stratification in familial hypercholesterolaemia

    PubMed Central

    Sharifi, Mahtab; Rakhit, Roby D; Humphries, Steve E; Nair, Devaki

    2016-01-01

    Familial hypercholesterolaemia (FH) is a common autosomal-dominant disorder in most European countries. Patients with FH are characterised by a raised level of low-density lipoprotein cholesterol and a high risk of premature coronary heart disease (CHD). Currently there is no consensus regarding the clinical utility to predict future coronary events or testing for the presence of subclinical atherosclerotic disease in asymptomatic patients with FH. Family screening of patients with FH as recommended by the UK National Institute of Health and Care Excellence guideline would result in finding many young individuals with a diagnosis of FH who are clinically asymptomatic. The traditional CHD risk scores, that is, the Framingham score, are insufficient in risk prediction in this group of young individuals. In addition, a better understanding of the genetic aetiology of the FH phenotype and CHD risk in monogenic FH and polygenic hypercholesterolaemia is needed. Non-invasive imaging methods such as carotid intima-media thickness measurement might produce more reliable information in finding high-risk patients with FH. The potential market authorisation of novel therapeutic agents such as PCSK9 monoclonal inhibitors makes it essential to have a better screening programme to prioritise the candidates for treatment with the most severe form of FH and at higher risk of coronary events. The utility of new imaging techniques and new cardiovascular biomarkers remains to be determined in prospective trials. PMID:27126396

  1. Risk Stratification System for Oral Cancer Screening.

    PubMed

    Pereira, Lutécia H Mateus; Reis, Isildinha M; Reategui, Erika P; Gordon, Claudia; Saint-Victor, Sandra; Duncan, Robert; Gomez, Carmen; Bayers, Stephanie; Fisher, Penelope; Perez, Aymee; Goodwin, W Jarrard; Hu, Jennifer J; Franzmann, Elizabeth J

    2016-06-01

    Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in incidence. Worldwide 5-year survival is only 50% due to delayed intervention with more than half of the diagnoses at stage III and IV, whereas earlier detection (stage I and II) yields survival rates up to 80% to 90%. Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels may facilitate oral cancer risk assessment and early intervention. This study used a hospital-based design with 150 cases and 150 frequency-matched controls to determine whether CD44 and total protein levels in oral rinses were associated with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol use, and socioeconomic status (SES). High-risk subjects receiving oral cancer prevention interventions as part of a community-based program (n = 150) were followed over 1 year to determine marker specificity and variation. CD44 ≥5.33 ng/mL was highly associated with case status [adjusted OR 14.489; 95% confidence interval (CI), 5.973-35.145; P < .0001, vs. reference group CD44 <2.22 ng/mL and protein <1.23 mg/mL]. Total protein aided prediction above CD44 alone. Sensitivity and specificity in the frequency-matched study was 80% and 48.7%, respectively. However, controls were not representative of the target screening population due, in part, to a high rate of prior cancer. In contrast, specificity in the high-risk community was 74% and reached 95% after annual retesting. Simple and inexpensive salivary CD44 and total protein measurements may help identify individuals at heightened risk for oral cancer from the millions who partake in risky behaviors. Cancer Prev Res; 9(6); 445-55. ©2016 AACR. PMID:27020654

  2. [Ventricular preexcitation: is risk stratification feasible?].

    PubMed

    De Rosa, Francesco; Mancuso, Paola; Chiatto, Mario; Calvelli, Antonio; De Donato, Vincenzo; Mazza, Salvatore; Spadafora, Gabriele

    2010-04-01

    The Wolff-Parkinson-White syndrome is a current debated clinical issue. Although the anatomical characteristics, polymorphic electrocardiographic features, and electrophysiological mechanisms of arrhythmias and sudden cardiac death are well known, the identification of patients at risk of sudden cardiac death remains challenging. Owing to the lack of effective therapeutic strategies, in the pre-ablation era many studies have been conducted to define the prognostic value of clinical and instrumental tests, and to define the actual risk of sudden cardiac death in patients with ventricular preexcitation. Nowadays, radiofrequency transcatheter ablation of anomalous atrioventricular pathways is a strong therapeutic option for all patients, independent of the risk of sudden cardiac death. However, radiofrequency ablation is associated with serious complications, but many studies confirm an overall good prognosis for most of the patients with electrocardiographic pattern of ventricular preexcitation. The aim of this review is to assess the prognostic value of clinical and instrumental tests in patients with ventricular preexcitation, referring to the latest knowledge. PMID:20677574

  3. Percutaneous biopsy for risk stratification of renal masses

    PubMed Central

    Blute, Michael L.; Drewry, Anna

    2015-01-01

    The increased use of abdominal imaging has led to identification of more patients with incidental renal masses, and renal mass biopsy (RMB) has become a popular method to evaluate unknown renal masses prior to definitive treatment. Pathologic data obtained from biopsy may be used to guide decisions for treatment and may include the presence or absence of malignant tumor, renal cell cancer subtype, tumor grade and the presence of other aggressive pathologic features. However, prior to using RMB for risk stratification, it is important to understand whether RMB findings are equivalent to pathologic analysis of surgical specimens and to identify any potential limitations of this approach. This review outlines the advantages and limitations of the current studies that evaluate RMB as a guide for treatment decision in patients with unknown renal masses. In multiple series, RMB has demonstrated low morbidity and a theoretical reduction in cost, if patients with benign tumors are identified from biopsy and can avoid subsequent treatment. However, when considering the routine use of RMB for risk stratification, it is important to note that biopsy may underestimate risk in some patients by undergrading, understaging or failing to identify aggressive tumor features. Future studies should focus on developing treatment algorithms that integrate RMB to identify the optimal use in risk stratification of patients with unknown renal masses. PMID:26425141

  4. Quantitative risk stratification of oral leukoplakia with exfoliative cytology.

    PubMed

    Liu, Yao; Li, Jianying; Liu, Xiaoyong; Liu, Xudong; Khawar, Waqaar; Zhang, Xinyan; Wang, Fan; Chen, Xiaoxin; Sun, Zheng

    2015-01-01

    Exfoliative cytology has been widely used for early diagnosis of oral squamous cell carcinoma (OSCC). Test outcome is reported as "negative", "atypical" (defined as abnormal epithelial changes of uncertain diagnostic significance), and "positive" (defined as definitive cellular evidence of epithelial dysplasia or carcinoma). The major challenge is how to properly manage the "atypical" patients in order to diagnose OSCC early and prevent OSCC. In this study, we collected exfoliative cytology data, histopathology data, and clinical data of normal subjects (n=102), oral leukoplakia (OLK) patients (n=82), and OSCC patients (n=93), and developed a data analysis procedure for quantitative risk stratification of OLK patients. This procedure involving a step called expert-guided data transformation and reconstruction (EdTAR) which allows automatic data processing and reconstruction and reveals informative signals for subsequent risk stratification. Modern machine learning techniques were utilized to build statistical prediction models on the reconstructed data. Among the several models tested using resampling methods for parameter pruning and performance evaluation, Support Vector Machine (SVM) was found to be optimal with a high sensitivity (median>0.98) and specificity (median>0.99). With the SVM model, we constructed an oral cancer risk index (OCRI) which may potentially guide clinical follow-up of OLK patients. One OLK patient with an initial OCRI of 0.88 developed OSCC after 40 months of follow-up. In conclusion, we have developed a statistical method for qualitative risk stratification of OLK patients. This method may potentially improve cost-effectiveness of clinical follow-up of OLK patients, and help design clinical chemoprevention trial for high-risk populations. PMID:25978541

  5. QT variability improves risk stratification in patients with dilated cardiomyopathy.

    PubMed

    Fischer, C; Seeck, A; Schroeder, R; Goernig, M; Schirdewan, A; Figulla, H R; Baumert, M; Voss, A

    2015-04-01

    Recently it could be demonstrated that systolic and diastolic blood pressure variability (BPV) as well as segmented Poincare plot analysis (SPPA) contribute to risk stratification in patients suffering from dilated cardiomyopathy (DCM). The aim of this study was to improve the risk stratification applying a multivariate technique including QT variability (QTV). We enrolled and significantly separated 56 low risk and 13 high risk DCM patients by nearly all applied BPV and QTV methods, but not with traditional heart rate variability analysis. The optimum set of two indices calculating the multivariate discriminate analysis (DA) included one BPV index calculated by symbolic dynamics method (DBP(Shannon)) and one index calculated from QTV (QTV(log)) achieving an area under the receiver operating characteristics curve (AUC) of 92%, sensitivity of 92.3% and specificity of 89.3%. Performing only electrocardiogram analysis, the optimum multivariate approach including indices from segmented Poincaré plot analysis and QTV still achieved a remarkable AUC of 88.3%. Increasing the number of indices for multivariate DA up to three, we achieved an AUC of 95.7%, sensitivity of 100% and specificity of 85.7% including one clinical, one BPV and one QTV index. Summarizing, we identified DCM patients with an increased risk of sudden cardiac death applying QTV analysis in a multivariate approach. PMID:25799313

  6. [Lung cancer screening - risk stratification : Who should undergo screening?].

    PubMed

    Beer, L; Prosch, H

    2016-09-01

    Lung cancer is one of the leading causes of deaths in Europa and the USA. In approximately 75 % of lung cancer patients, bronchogenic carcinoma is detected at an advanced tumor stage; therefore, therapeutic options which aim at curing the disease in these patients are limited and treatment is mostly palliative. A relatively good prognosis is reserved for the minority of patients where the tumor is detected at an early stage and treatment is potentially curative. For this reason, early diagnosis of lung cancer could save lives. Retrospective analyses of the US national lung screening trial (NLST) showed that especially high-risk populations (e. g. higher age, positive smoking history, overweight and a positive family history for lung cancer) benefit most from lung cancer screening. Thus, the effectiveness of computed tomography (CT) screening can be improved by focusing on high-risk populations. This review article summarizes the risk stratification models of the large European and American screening studies and discusses possible future biomarkers for risk stratification. PMID:27495786

  7. Risk stratification for wilms tumor: current approach and future directions.

    PubMed

    Dome, Jeffrey S; Perlman, Elizabeth J; Graf, Norbert

    2014-01-01

    Wilms tumor, or nephroblastoma, has provided a paradigm for progressive improvement in clinical outcomes achieved through serial cooperative group studies. With modern surgery, chemotherapy, and radiation therapy approaches, the overall survival rate for patients with Wilms tumor has reached 90%. Remarkably, the increase in survival has been achieved with a reduction in therapy for most patient subgroups, leading not only to more survivors, but also to healthier survivors. A key contributor to improved outcomes has been the development of clinical and biologic prognostic markers that have enabled risk-directed therapy. Whereas the early cooperative group studies used only tumor stage for risk stratification, current Children's Oncology Group (COG) and International Society of Pediatric Oncology (SIOP) protocols employ a multitude of prognostic factors to guide therapy. Prognostic factors used in the current generation of COG studies include stage, histology, patient age, tumor weight, completeness of lung nodule response, and loss of heterozygosity at chromosomes 1p and 16q. Future COG studies seek to incorporate gain of chromosome 1q and methylation pattern of chromosome 11p15 into the risk classification schema. Prognostic factors used in the current SIOP studies include stage, histology, tumor volume, and responsiveness to therapy. Future SIOP studies seek to incorporate absolute blastemal volume and novel molecular markers for resistant blastema into the risk stratification approach. PMID:24857079

  8. Noninvasive Risk Stratification of Lung Adenocarcinoma using Quantitative Computed Tomography

    PubMed Central

    Raghunath, Sushravya; Maldonado, Fabien; Rajagopalan, Srinivasan; Karwoski, Ronald A.; DePew, Zackary S.; Bartholmai, Brian J.; Peikert, Tobias; Robb, Richard A.

    2014-01-01

    Introduction Lung cancer remains the leading cause of cancer-related deaths in the US and worldwide. Adenocarcinoma is the most common type of lung cancer and encompasses lesions with widely variable clinical outcomes. In the absence of noninvasive risk stratification, individualized patient management remains challenging. Consequently a subgroup of pulmonary nodules of the lung adenocarcinoma spectrum is likely treated more aggressively than necessary. Methods Consecutive patients with surgically resected pulmonary nodules of the lung adenocarcinoma spectrum (lesion size ≤ 3 cm, 2006–2009) and available pre-surgical high-resolution computed tomography (HRCT) imaging were identified at Mayo Clinic Rochester. All cases were classified using an unbiased Computer-Aided Nodule Assessment and Risk Yield (CANARY) approach based on the quantification of pre-surgical HRCT characteristics. CANARY-based classification was independently correlated to postsurgical progression-free survival. Results CANARY analysis of 264 consecutive patients identified three distinct subgroups. Independent comparisons of 5-year disease-free survival (DFS) between these subgroups demonstrated statistically significant differences in 5-year DFS, 100%, 72.7% and 51.4%, respectively (p = 0.0005). Conclusions Non-invasive CANARY based risk stratification identifies subgroups of patients with pulmonary nodules of the adenocarcinoma spectrum characterized by distinct clinical outcomes. This technique may ultimately improve the current expert opinion-based approach to the management of these lesions by facilitating individualized patient management. PMID:25170645

  9. Novel biomarkers for risk stratification and identification of life-threatening cardiovascular disease: troponin and beyond.

    PubMed

    Razzouk, Louai; Fusaro, Mario; Esquitin, Ricardo

    2012-05-01

    Chest pain and other symptoms that may represent acute coronary syndromes (ACS) are common reasons for emergency department (ED) presentations, accounting for over six million visits annually in the United States [1]. Chest pain is the second most common ED presentation in the United States. Delays in diagnosis and inaccurate risk stratification of chest pain can result in serious morbidity and mortality from ACS, pulmonary embolism (PE), aortic dissection and other serious pathology. Because of the high morbidity, mortality, and liability issues associated with both recognized and unrecognized cardiovascular pathology, an aggressive approach to the evaluation of this patient group has become the standard of care. Clinical history, physical examination and electrocardiography have a limited diagnostic and prognostic role in the evaluation of possible ACS, PE, and aortic dissection, so clinicians continue to seek more accurate means of risk stratification. Recent advances in diagnostic imaging techniques particularly computed-tomography of the coronary arteries and aorta, have significantly improved our ability to diagnose life-threatening cardiovascular disease. In an era where health care utilization and cost are major considerations in how disease is managed, it is crucial to risk-stratify patients quickly and efficiently. Historically, biomarkers have played a significant role in the diagnosis and risk stratification of several cardiovascular disease states including myocardial infarction, congestive heart failure, and pulmonary embolus. Multiple biomarkers have shown early promise in answering questions of risk stratification and early diagnosis of cardiovascular pathology however many do not yet have wide clinical availability. The goal of this review will be to discuss these novel biomarkers and describe their potential role in direct patient care. PMID:22708908

  10. Risk stratification for benign prostatic hyperplasia (BPH) treatment.

    PubMed

    Emberton, Mark; Fitzpatrick, John M; Rees, Jon

    2011-03-01

    • Benign prostatic hyperplasia (BPH) is a common cause of bothersome lower urinary tract symptoms. In the past, the aim of drug treatment was to relieve symptoms until surgery became necessary, predominantly using an α-blocker or a 5α-reductase inhibitor (5ARI) as monotherapy. • Together with improving knowledge about the pathogenesis of BPH, there is now strong evidence from large randomized trials that risk stratification and appropriate treatment with combined α-blocker/5ARI therapy can significantly reduce the risk of disease progression and avoid long-term complications such as acute urinary retention and surgery. • BPH will increasingly be managed in primary care in the future and, if new management strategies based on this evidence are to be implemented cost effectively, there is a need to introduce shared care between the primary and secondary care sectors to optimise use of resources and expertise. PMID:21265993

  11. Phenotypes of prediabetes and stratification of cardiometabolic risk.

    PubMed

    Stefan, Norbert; Fritsche, Andreas; Schick, Fritz; Häring, Hans-Ulrich

    2016-09-01

    Prediabetes is associated with increased risks of type 2 diabetes, cardiovascular disease, dementia, and cancer, and its prevalence is increasing worldwide. Lifestyle and pharmacological interventions in people with prediabetes can prevent the development of diabetes and possibly cardiovascular disease. However, prediabetes is a highly heterogeneous metabolic state, both with respect to its pathogenesis and prediction of disease. Improved understanding of these features and precise phenotyping of prediabetes could help to improve stratification of disease risk. In this Personal View, we focus on the extreme metabolic phenotypes of metabolically healthy obesity and metabolically unhealthy normal weight, insulin secretion failure, insulin resistance, visceral obesity, and non-alcoholic fatty liver disease. We present new analyses aimed at improving characterisation of phenotypes in lean, overweight, and obese people with prediabetes. We discuss evidence from lifestyle intervention studies to explore whether these phenotypes can also be used for individualised prediction and prevention of cardiometabolic diseases. PMID:27185609

  12. Left Ventricular Diameter and Risk Stratification for Sudden Cardiac Death

    PubMed Central

    Narayanan, Kumar; Reinier, Kyndaron; Teodorescu, Carmen; Uy‐Evanado, Audrey; Aleong, Ryan; Chugh, Harpriya; Nichols, Gregory A.; Gunson, Karen; London, Barry; Jui, Jonathan; Chugh, Sumeet S.

    2014-01-01

    Background Left ventricular (LV) diameter is routinely measured on the echocardiogram but has not been jointly evaluated with the ejection fraction (EF) for risk stratification of sudden cardiac death (SCD). Methods and Results From a large ongoing community‐based study of SCD (The Oregon Sudden Unexpected Death Study; population ≈1 million), SCD cases were compared with geographic controls. LVEF and LV diameter, measured using the LV internal dimension in diastole (categorized as normal, mild, moderate, or severe dilatation using American Society of Echocardiography definitions) were assessed from echocardiograms prior but unrelated to the SCD event. Cases (n=418; 69.5±13.8 years), compared with controls (n=329; 67.7±11.9 years), more commonly had severe LV dysfunction (EF ≤35%; 30.5% versus 18.8%; P<0.01) and larger LV diameter (52.2±10.5 mm versus 49.7±7.9 mm; P<0.01). Moderate or severe LV dilatation (16.3% versus 8.2%; P=0.001) and severe LV dilatation (8.1% versus 2.1%; P<0.001) were significantly more frequent in cases. In multivariable analysis, severe LV dilatation was an independent predictor of SCD (odds ratio 2.5 [95% CI 1.03 to 5.9]; P=0.04). In addition, subjects with both EF ≤35% and severe LV dilatation had higher odds for SCD compared with those with low EF only (odds ratio 3.8 [95% CI 1.5 to 10.2] for both versus 1.7 [95% CI 1.2 to 2.5] for low EF only), suggesting that severe LV dilatation additively increased SCD risk. Conclusion LV diameter may contribute to risk stratification for SCD independent of the LVEF. This readily available echocardiographic measure warrants further prospective evaluation. PMID:25227407

  13. Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification.

    PubMed

    Toczek, Jakub; Meadows, Judith L; Sadeghi, Mehran M

    2016-01-01

    Selection of patients for abdominal aortic aneurysm repair is currently based on aneurysm size, growth rate, and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, for example, inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in abdominal aortic aneurysm morbidity and mortality. (18)F-fluorodeoxyglucose-positron emission tomography and ultrasmall superparamagnetic particles of iron oxide magnetic resonance imaging are 2 novel approaches to abdominal aortic aneurysm imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (eg, integrin αvβ3 and matrix metalloproteinases), have proven effective in preclinical models of abdominal aortic aneurysm and show great potential for clinical translation. PMID:26763279

  14. Risk Stratification for Sudden Cardiac Death: Current Approaches and Predictive Value

    PubMed Central

    Lopera, Gustavo; Curtis, Anne B.

    2009-01-01

    Sudden cardiac death (SCD) is a serious public health problem; the annual incidence of out-of-hospital cardiac arrest in North America is approximately 166,200. Identifying patients at risk is a difficult proposition. At the present time, left ventricular ejection fraction (LVEF) remains the single most important marker for risk stratification. According to current guidelines, most patients with LVEF <35% could benefit from prophylactic ICD implantation, particularly in the setting of symptomatic heart failure. Current risk stratification strategies fail to identify patients at risk of SCD in larger population groups encompassing a greater number of potential SCD victims. However, the best approach to identifying patients and the value of various risk stratification tools is not entirely clear. The goal of this review is to discuss the problem of SCD and the value of the different risk stratification markers and their potential clinical use either alone or in combination with other risk stratification markers. PMID:20066150

  15. The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence

    PubMed Central

    Walczyk, Agnieszka; Pałyga, Iwona; Gąsior-Perczak, Danuta; Gadawska-Juszczyk, Klaudia; Szymonek, Monika; Trybek, Tomasz; Lizis-Kolus, Katarzyna; Szyska-Skrobot, Dorota; Mikina, Estera; Hurej, Stefan; Słuszniak, Janusz; Mężyk, Ryszard; Góźdź, Stanisław

    2016-01-01

    Context There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course. Materials and Methods This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system. Results The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases). Conclusions The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification. PMID:27078258

  16. A new gender-specific model for skin autofluorescence risk stratification.

    PubMed

    Ahmad, Muhammad S; Damanhouri, Zoheir A; Kimhofer, Torben; Mosli, Hala H; Holmes, Elaine

    2015-01-01

    Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79-4.84 AU) and 2.20 AU (0.75-4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis. PMID:25974028

  17. Arrhythmogenic Right Ventricular Cardiomyopathy: Risk Stratification and Indications for Defibrillator Therapy.

    PubMed

    Zorzi, Alessandro; Rigato, Ilaria; Bauce, Barbara; Pilichou, Kalliopi; Basso, Cristina; Thiene, Gaetano; Iliceto, Sabino; Corrado, Domenico

    2016-06-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined disease which predisposes to life-threatening ventricular arrhythmias. The main goal of ARVC therapy is prevention of sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) is the most effective therapy for interruption of potentially lethal ventricular tachyarrhythmias. Despite its life-saving potential, ICD implantation is associated with a high rate of complications and significant impact on quality of life. Accurate risk stratification is needed to identify individuals who most benefit from the therapy. While there is general agreement that patients with a history of cardiac arrest or hemodynamically unstable ventricular tachycardia are at high risk of SCD and needs an ICD, indications for primary prevention remain a matter of debate. The article reviews the available scientific evidence and guidelines that may help to stratify the arrhythmic risk of ARVC patients and guide ICD implantation. Other therapeutic strategies, either alternative or additional to ICD, will be also addressed. PMID:27147509

  18. Prostate cancer risk stratification with magnetic resonance imaging.

    PubMed

    Felker, Ely R; Margolis, Daniel J; Nassiri, Nima; Marks, Leonard S

    2016-07-01

    In recent years, multiparametric magnetic resonance imaging (mpMRI) has shown promise for prostate cancer (PCa) risk stratification. mpMRI, often followed by targeted biopsy, can be used to confirm low-grade disease before enrollment in active surveillance. In patients with intermediate or high-risk PCa, mpMRI can be used to inform surgical management. mpMRI has sensitivity of 44% to 87% for detection of clinically significant PCa and negative predictive value of 63% to 98% for exclusion of significant disease. In addition to tumor identification, mpMRI has also been shown to contribute significant incremental value to currently used clinical nomograms for predicting extraprostatic extension. In combination with conventional clinical criteria, accuracy of mpMRI for prediction of extraprostatic extension ranges from 92% to 94%, significantly higher than that achieved with clinical criteria alone. Supplemental sequences, such as diffusion-weighted imaging and dynamic contrast-enhanced imaging, allow quantitative evaluation of cancer-suspicious regions. Apparent diffusion coefficient appears to be an independent predictor of PCa aggressiveness. Addition of apparent diffusion coefficient to Epstein criteria may improve sensitivity for detection of significant PCa by as much as 16%. Limitations of mpMRI include variability in reporting, underestimation of PCa volume and failure to detect clinically significant disease in a small but significant number of cases. PMID:27040381

  19. Risk stratification after acute myocardial infarction in the reperfusion era.

    PubMed

    Michaels, A D; Goldschlager, N

    2000-01-01

    Historically, risk stratification for survivors of acute myocardial infarction (AMI) has centered on 3 principles: assessment of left ventricular function, detection of residual myocardial ischemia, and estimation of the risk for sudden cardiac death. Although these factors still have important prognostic implications for these patients, our ability to predict adverse cardiac events has significantly improved over the last several years. Recent studies have identified powerful predictors of adverse cardiac events available from the patient history, physical examination, initial electrocardiogram, and blood testing early in the evaluation of patients with AMI. Numerous studies performed in patients receiving early reperfusion therapy with either thrombolysis or primary angioplasty have emphasized the importance of a patent infarct related artery for long-term survival. The predictive value of a variety of noninvasive and invasive tests to predict myocardial electrical instability have been under active investigation in patients receiving early reperfusion therapy. The current understanding of the clinically important predictors of clinical outcomes in survivors of AMI is reviewed in this article. PMID:10661780

  20. Cardiac risk stratification in cardiac rehabilitation programs: a review of protocols

    PubMed Central

    da Silva, Anne Kastelianne França; Barbosa, Marianne Penachini da Costa de Rezende; Bernardo, Aline Fernanda Barbosa; Vanderlei, Franciele Marques; Pacagnelli, Francis Lopes; Vanderlei, Luiz Carlos Marques

    2014-01-01

    Objective Gather and describe general characteristics of different protocols of risk stratification for cardiac patients undergoing exercise. Methods We conducted searches in LILACS, IBECS, MEDLINE, Cochrane Library, and SciELO electronic databases, using the following descriptors: Cardiovascular Disease, Rehabilitation Centers, Practice Guideline, Exercise and Risk Stratification in the past 20 years. Results Were selected eight studies addressing methods of risk stratification in patients undergoing exercise. Conclusion None of the methods described could cover every situation the patient can be subjected to; however, they are essential to exercise prescription. PMID:25140477

  1. Early risk stratification in pediatric type 1 diabetes.

    PubMed

    Broe, Rebecca

    2015-03-01

    of early glycemic control. Identifying high-risk patients at a very early stage is not only desired for prevention of diabetic retinopathy - neuropathy and nephropathy similarly remain frequent in type 1 diabetes. Early risk stratification will allow for timely implementation of effective interventions and for individualized screening and diabetes care. The second and third studies of this thesis provide the longest prospective studies to date on both retinal vessel calibers and retinal fractal dimensions and their predictive value on diabetic microvascular complications. Semi-automated computer software has been developed to measure smaller changes in the retinal vessels on retinal photographs. Two of the first parameters to be reliably estimated by these programs were retinal vessel calibers and retinal vascular fractal dimensions (a quantitative measure on vascular complexity). There is very limited knowledge on their predictive value on diabetic complications thus far. In the second and third study, a consistent relation between narrower retinal arteriolar calibers, wider retinal venular calibers, lower fractal dimensions and the 16-year incidences of diabetic neuropathy, nephropathy and proliferative retinopathy was found. This has never been shown before. The results on vessel analyzes provides indications of a common pathogenic pathway for diabetic microvascular complications and therefore a possibility of universal risk estimation for development of neuropathy, nephropathy and retinopathy in type 1 diabetes. PMID:25703648

  2. Integration of genetic and epigenetic markers for risk stratification: opportunities and challenges

    PubMed Central

    Pashayan, Nora; Reisel, Daniel; Widschwendter, Martin

    2016-01-01

    Summary Common genetic susceptibility variants could be used for risk stratification in risk-tailored cancer screening and prevention programmes. Combining genetic variants with environmental risk factors would improve risk stratification. Epigenetic changes are surrogate markers of environmental exposures during individual’s lifetime. Integrating epigenetic markers, in lieu of environmental exposure data, with genetic markers would potentially improve risk stratification. Epigenetic changes are reversible and acquired gradually, providing potentials for prevention and early detection strategies. The epigenetic changes are tissue-specific and stage-of-development-specific, raising challenges in choice of sample and timing for evaluation of cancer-associated changes. The Horizon 2020 funded research programme, FORECEE, using empirical data, will investigate the value of integration of epigenomics with genomics for risk prediction and prevention of women-specific cancers. PMID:27053939

  3. [Cardiovascular risk assessment and risk stratification- guided therapy: predict, prevent and individualize].

    PubMed

    Ural, Dilek

    2011-09-01

    Modern concept in primary prevention of cardiovascular diseases (CVD) entails assessing the person's global risk and making the right management in accordance with these results. Correspondingly, 3 steps recommended for the prevention of CVD under risk guidance are: (a) risk assessment via a proper system like Framingham Risk Score, SCORE, QRISK, PROCAM; (b) decision-making in the proper management in terms of informing the patient about lifestyle changes that he or she can cope and drug selection; and (c) evaluation of treatment decision in terms of cost effectiveness. Although, a significant decline is observed in CVD morbidity and mortality, particularly in the western countries, we still are trying to approach to competent quality measures about management under CV risk guidance. This review summarizes the main challenges regarding risk stratification-guided management strategy in primary prevention of CVD. PMID:21821497

  4. A new comorbidities index for risk stratification for treatment of unruptured cerebral aneurysms.

    PubMed

    Newman, William C; Neal, Dan W; Hoh, Brian L

    2016-09-01

    OBJECTIVE Comorbidities have an impact on risk stratification for outcomes in analyses of large patient databases. Although the Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) are the most commonly used comorbidity indexes, these have not been validated for patients with unruptured cerebral aneurysms; therefore, the authors created a comorbidity index specific to these patients. METHODS The authors extracted all records involving unruptured cerebral aneurysms treated with clipping, coiling, or both from the Nationwide Inpatient Sample (2002-2010). They assessed the effect of 37 variables on poor outcome and used the results to create a risk score for these patients. The authors used a validation data set and bootstrapping to evaluate the new index and compared it to CCI and ECI in prediction of poor outcome, mortality, length of stay, and hospital charges. RESULTS The index assigns integer values (-2 to 7) to 20 comorbidities: neurological disorder, renal insufficiency, gastrointestinal bleeding, paralysis, acute myocardial infarction, electrolyte disorder, weight loss, metastatic cancer, drug abuse, arrhythmia, coagulopathy, cerebrovascular accident, psychosis, alcoholism, perivascular disease, valvular disease, tobacco use, hypothyroidism, depression, and hypercholesterolemia. Values are summed to determine a patient's risk score. The new index was better at predicting poor outcome than CCI or ECI (area under the receiver operating characteristic curve [AUC] 0.814 [95% CI 0.798-0.830], vs 0.694 and 0.712, respectively, for the other indices), and it was also better at predicting mortality (AUC 0.775 [95% CI 0.754-0.792], vs 0.635 and 0.657, respectively, for CCI and ECI). CONCLUSIONS This new comorbidity index outperforms the CCI and ECI in predicting poor outcome, mortality, length of stay, and total charges for patients with unruptured cerebral aneurysm. Reevaluation of other patient cohorts is warranted to determine the impact of

  5. ETHNOPRED: a novel machine learning method for accurate continental and sub-continental ancestry identification and population stratification correction

    PubMed Central

    2013-01-01

    Background Population stratification is a systematic difference in allele frequencies between subpopulations. This can lead to spurious association findings in the case–control genome wide association studies (GWASs) used to identify single nucleotide polymorphisms (SNPs) associated with disease-linked phenotypes. Methods such as self-declared ancestry, ancestry informative markers, genomic control, structured association, and principal component analysis are used to assess and correct population stratification but each has limitations. We provide an alternative technique to address population stratification. Results We propose a novel machine learning method, ETHNOPRED, which uses the genotype and ethnicity data from the HapMap project to learn ensembles of disjoint decision trees, capable of accurately predicting an individual’s continental and sub-continental ancestry. To predict an individual’s continental ancestry, ETHNOPRED produced an ensemble of 3 decision trees involving a total of 10 SNPs, with 10-fold cross validation accuracy of 100% using HapMap II dataset. We extended this model to involve 29 disjoint decision trees over 149 SNPs, and showed that this ensemble has an accuracy of ≥ 99.9%, even if some of those 149 SNP values were missing. On an independent dataset, predominantly of Caucasian origin, our continental classifier showed 96.8% accuracy and improved genomic control’s λ from 1.22 to 1.11. We next used the HapMap III dataset to learn classifiers to distinguish European subpopulations (North-Western vs. Southern), East Asian subpopulations (Chinese vs. Japanese), African subpopulations (Eastern vs. Western), North American subpopulations (European vs. Chinese vs. African vs. Mexican vs. Indian), and Kenyan subpopulations (Luhya vs. Maasai). In these cases, ETHNOPRED produced ensembles of 3, 39, 21, 11, and 25 disjoint decision trees, respectively involving 31, 502, 526, 242 and 271 SNPs, with 10-fold cross validation accuracy of

  6. Performance And Agreement Of Risk Stratification Instruments For Postoperative Delirium In Persons Aged 50 Years Or Older

    PubMed Central

    Jansen, Carolien J.; Absalom, Anthony R.; de Bock, Geertruida H.; van Leeuwen, Barbara L.; Izaks, Gerbrand J.

    2014-01-01

    Several risk stratification instruments for postoperative delirium in older people have been developed because early interventions may prevent delirium. We investigated the performance and agreement of nine commonly used risk stratification instruments in an independent validation cohort of consecutive elective and emergency surgical patients aged ≥50 years with ≥1 risk factor for postoperative delirium. Data was collected prospectively. Delirium was diagnosed according to DSM-IV-TR criteria. The observed incidence of postoperative delirium was calculated per risk score per risk stratification instrument. In addition, the risk stratification instruments were compared in terms of area under the receiver operating characteristic (ROC) curve (AUC), and positive and negative predictive value. Finally, the positive agreement between the risk stratification instruments was calculated. When data required for an exact implementation of the original risk stratification instruments was not available, we used alternative data that was comparable. The study population included 292 patients: 60% men; mean age (SD), 66 (8) years; 90% elective surgery. The incidence of postoperative delirium was 9%. The maximum observed incidence per risk score was 50% (95%CI, 15–85%); for eight risk stratification instruments, the maximum observed incidence per risk score was ≤25%. The AUC (95%CI) for the risk stratification instruments varied between 0.50 (0.36–0.64) and 0.66 (0.48–0.83). No AUC was statistically significant from 0.50 (p≥0.11). Positive predictive values of the risk stratification instruments varied between 0–25%, negative predictive values between 89–95%. Positive agreement varied between 0–66%. No risk stratification instrument showed clearly superior performance. In conclusion, in this independent validation cohort, the performance and agreement of commonly used risk stratification instruments for postoperative delirium was poor. Although some caution is

  7. Adjuvant Transarterial Chemoembolization Following Liver Resection for Intrahepatic Cholangiocarcinoma Based on Survival Risk Stratification

    PubMed Central

    Li, Jun; Wang, Qing; Lei, Zhengqing; Wu, Dong; Si, Anfeng; Wang, Kui; Wan, Xuying; Wang, Yizhou; Yan, Zhenlin; Xia, Yong; Lau, Wan Yee; Wu, Mengchao

    2015-01-01

    Background. The effectiveness of adjuvant transarterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study was performed to identify ICC patients who would benefit from adjuvant TACE. Patients and Methods. The study included 553 patients who underwent hepatectomy for ICC between January 2008 and February 2011 at the Eastern Hepatobiliary Surgery Hospital and who were treated with or without TACE (122 with TACE and 431 without TACE). Survival risk stratification was performed using the established prognostic nomogram (ICC nomogram). The predictive performance was evaluated by concordance index and calibration. The tumor recurrence and overall survival (OS) rates were analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). Results. The predictive performance of the ICC nomogram was demonstrated by the well-fitted calibration curves and an optimal c-index of 0.71 for OS prediction. In the whole cohort, the 5-year recurrence and OS rates between the TACE and non-TACE groups were significantly different (5-year recurrence: 72.9% vs. 78.1%; OS: 38.4% vs. 29.7%). After 1:1 PSM, the TACE and non-TACE groups (122 patients each) had similar 5-year recurrence and OS rates (5-year recurrence: 72.9% vs. 74.2%; OS: 38.4% vs. 36.0%). By survival risk stratification based on ICC nomogram, only the patients in the lowest tertile (nomogram scores ≥77) benefited from adjuvant TACE (TACE vs. non-TACE groups: 90.4% vs. 95.9% for 5-year recurrence; 21.3% vs. 6.2% for 5-year OS). Conclusion. Adjuvant TACE following liver resection might be suitable for ICC patients with high ICC nomogram scores (≥77). Implications for Practice: The accurate predictive performance of the established prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed in an independent cohort with 553 patients. Based on the survival risk stratification using the nomogram

  8. The Role of Biomarkers in the Diagnosis and Risk Stratification of Acute Graft-versus-Host Disease: A Systematic Review.

    PubMed

    Ali, Alaa M; DiPersio, John F; Schroeder, Mark A

    2016-09-01

    Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used curative modality for hematologic malignancies and other benign conditions. Attempts to reduce morbidity and mortality and improve survival in patients undergoing HCT are crucial. The ability to diagnose acute graft-versus-host disease (aGVHD) in a timely manner, or to even predict aGVHD before clinical manifestations, along with the accurate stratification of these patients, are critical steps to improve the treatment and outcomes of these patients. Many novel biomarkers that may help achieve these goals have been studied recently. This overview is intended to assist clinicians and investigators by providing a comprehensive review and analytical interpretation of the current knowledge concerning aGVHD and biomarkers likely to prove useful in diagnosis and risk stratification of this condition, along with the difficulties that hamper this approach. PMID:27158050

  9. Risk stratification of thyroid nodules on ultrasonography with the French TI-RADS: description and reflections

    PubMed Central

    2016-01-01

    The widespread use of ultrasonography places it in a key position for use in the risk stratification of thyroid nodules. The French proposal is a five-tier system, our version of a thyroid imaging reporting and database system (TI-RADS), which includes a standardized vocabulary and report and a quantified risk assessment. It allows the selection of the nodules that should be referred for fine-needle aspiration biopsies. Effort should be directed towards merging the different risk stratification systems utilized around the world and testing this unified system with multi-center studies. PMID:26324117

  10. Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction.

    PubMed

    Gatzoulis, Konstantinos A; Tsiachris, Dimitris; Arsenos, Petros; Tousoulis, Dimitris

    2016-01-26

    Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators (ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death. PMID:26839662

  11. Risk stratification by treadmill testing in acute myocardial infarction following thrombolytic therapy.

    PubMed

    Banerjee, A; Debnath, N B; Roy, S; Banerjee, A; Maity, A K

    1998-02-01

    Survivors of acute myocardial infarction (AMI) should have risk stratification for assessment of their future risk of cardiovascular events. One of the important means of risk stratification is by treadmill test (TMT). Most of the algorithms for assessment were done in the prethrombolytic era. But in the post-thrombolytic era, risk stratification by TMT should be properly evaluated. Fifty males with confirmed AMI with age ranging from 38-62 years (mean 48 years) were tested with a symptom limited (Modified Bruce Protocol) TMT. The patients were followed up for a minimum of 6 months (range 6-10 months). Out of 50 patients, 38 reported for follow up. Among them 22 (Group A) had cardiac events and 16 (Group B) had no events. Among the patients (Group A), 6 had unstable angina, 7 had reinfarction, 2 had sudden death, 4 had coronary artery bypass grafting (CABG) and 3 had angioplasty. Comparison between the two groups, A and B in TMT parameters like ST segment depression > 2.5 mm (12 vs 9), no. of leads where ST depression occurred (66 vs 48) during exercise, mean work capacity (8.1 vs 7.9 mets), mean systolic blood pressure response were all statistically insignificant. Though TMT was believed to be a good prognostic indicator to assess further cardiac events after AMI, its efficacy in risk stratification after thrombolysis is yet to be determined. This study does not show its worth in post MI risk assessment. PMID:11273111

  12. The need for improved risk stratification in chronic critical limb ischemia.

    PubMed

    Chung, Jayer; Modrall, J Gregory; Valentine, R James

    2014-12-01

    Vascular surgeons are well acquainted with chronic critical limb ischemia (CLI), the most severe manifestation of peripheral arterial disease, with patients presenting with ischemic rest pain or ulcerations, or both. Epidemiologic data predict a burgeoning epidemic of CLI within the United States, commensurate with the increasing incidence and prevalence of atherosclerotic risk factors, especially age and diabetes. Untreated, the risk of major amputation (above the ankle) or death, or both, ranges between 20% and 40% at 1 year. Current open and endovascular therapies have imperfect results, diverse treatment options, and recommendations that are often conflicting and confuse physicians, industry, and patients alike. The best treatment options are ideally evaluated by prospective, randomized controlled trials. However, these have proven impractical in CLI because the rapid evolution of devices and techniques has outstripped the ability to measure outcomes and compare treatment options. Alternatively, risk-stratifying models have been proposed to allow physicians, patients, and industry to objectively evaluate new therapeutics and devices as they evolve. These models are developed from prospective cohorts to identify and quantify variables that can subsequently predict outcome in individual patients. The risk stratification models can also compare CLI outcomes between physicians and institutions, supporting quality assessments, and compensation decisions within Accountable Care Organizations under the Affordable Health Care Act (ACA). Widespread adoption of risk-stratification schemes has yet to occur, despite the critical need for such a tool in CLI, because present models lack optimal predictive ability and generalizability. The passage of the ACA amplifies the importance of developing an improved risk-stratification tool to ensure equitable quality assessments and compensation. This review presents current risk-stratification models for CLI with a summary of the

  13. Cardiovascular Disease Risk amongst African Black Patients with Rheumatoid Arthritis: The Need for Population Specific Stratification

    PubMed Central

    Solomon, Ahmed; Tsang, Linda; Woodiwiss, Angela J.; Millen, Aletta M. E.; Norton, Gavin R.; Dessein, Patrick H.

    2014-01-01

    Rheumatoid arthritis (RA) enhances the risk of cardiovascular disease to a similar extent as diabetes. Whereas atherogenesis remains poorly elucidated in RA, traditional and nontraditional risk factors associate similarly and additively with CVD in RA. Current recommendations on CVD risk stratification reportedly have important limitations. Further, reported data on CVD and its risk factors derive mostly from data obtained in the developed world. An earlier epidemiological health transition is intrinsic to persons living in rural areas and those undergoing urbanization. It is therefore conceivable that optimal CVD risk stratification differs amongst patients with RA from developing populations compared to those from developed populations. Herein, we briefly describe current CVD and its risk factor profiles in the African black population at large. Against this background, we review reported data on CVD risk and its potential stratification amongst African black compared to white patients with RA. Routinely assessed traditional and nontraditional CVD risk factors were consistently and independently related to atherosclerosis in African white but not black patients with RA. Circulating concentrations of novel CVD risk biomarkers including interleukin-6 and interleukin-5 adipokines were mostly similarly associated with both endothelial activation and atherosclerosis amongst African black and white RA patients. PMID:25157371

  14. Risk stratification of Ramadan fasting in person with diabetes.

    PubMed

    AlArouj, Monira

    2015-05-01

    The world population comprises of 23% Muslims. Ramadan is the holy month of the Islamic year during which all healthy Muslims observe fasts. Although children and sick people are exempted from fasting but many of this group, want to observe fasts despite the medical advice against it. This includes a subset of people with diabetes which carries a considerable risk. Hypoglycaemia and hyperglycaemia are among the main hazards. Majority of Muslims with diabetes can fast safely during Ramadan; However some are placed at a greater risk. Pre-Ramadan risk assessment, structured education and selection of appropriate medication has shown to minimize the risks associated with fasting among people with diabetes. PMID:26013777

  15. Refining Breast Cancer Risk Stratification: Additional Genes, Additional Information.

    PubMed

    Kurian, Allison W; Antoniou, Antonis C; Domchek, Susan M

    2016-01-01

    Recent advances in genomic technology have enabled far more rapid, less expensive sequencing of multiple genes than was possible only a few years ago. Advances in bioinformatics also facilitate the interpretation of large amounts of genomic data. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). Although these new multiple-gene panel tests are used in oncology practice, questions remain about the clinical validity and the clinical utility of their results. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. Risk-adapted screening and prevention protocols are underway, with ongoing refinement as genetic knowledge grows. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival. PMID:27249685

  16. IMWG consensus on risk stratification in multiple myeloma.

    PubMed

    Chng, W J; Dispenzieri, A; Chim, C-S; Fonseca, R; Goldschmidt, H; Lentzsch, S; Munshi, N; Palumbo, A; Miguel, J S; Sonneveld, P; Cavo, M; Usmani, S; Durie, B G M; Avet-Loiseau, H

    2014-02-01

    Multiple myeloma is characterized by underlying clinical and biological heterogeneity, which translates to variable response to treatment and outcome. With the recent increase in treatment armamentarium and the projected further increase in approved therapeutic agents in the coming years, the issue of having some mechanism to dissect this heterogeneity and rationally apply treatment is coming to the fore. A number of robustly validated prognostic markers have been identified and the use of these markers in stratifying patients into different risk groups has been proposed. In this consensus statement, the International Myeloma Working Group propose well-defined and easily applicable risk categories based on current available information and suggests the use of this set of prognostic factors as gold standards in all clinical trials and form the basis of subsequent development of more complex prognostic system or better prognostic factors. At the same time, these risk categories serve as a framework to rationalize the use of therapies. PMID:23974982

  17. Delirium risk stratification in consecutive unselected admissions to acute medicine: validation of externally derived risk scores

    PubMed Central

    Pendlebury, Sarah T.; Lovett, Nicola; Smith, Sarah C.; Cornish, Emily; Mehta, Ziyah; Rothwell, Peter M.

    2016-01-01

    Background: reliable delirium risk stratification will aid recognition, anticipation and prevention and will facilitate targeting of resources in clinical practice as well as identification of at-risk patients for research. Delirium risk scores have been derived for acute medicine, but none has been prospectively validated in external cohorts. We therefore aimed to determine the reliability of externally derived risk scores in a consecutive cohort of older acute medicine patients. Methods: consecutive patients aged ≥65 over two 8-week periods (2010, 2012) were screened prospectively for delirium using the Confusion Assessment Method (CAM), and delirium was diagnosed using the DSM IV criteria. The reliability of existing delirium risk scores derived in acute medicine cohorts and simplified for use in routine clinical practice (USA, n = 2; Spain, n = 1; Indonesia, n = 1) was determined by the area under the receiver operating characteristic curve (AUC). Delirium was defined as prevalent (on admission), incident (occurring during admission) and any (prevalent + incident) delirium. Results: among 308 consecutive patients aged ≥65 (mean age/SD = 81/8 years, 164 (54%) female), existing delirium risk scores had AUCs for delirium similar to those reported in their original internal validations ranging from 0.69 to 0.76 for any delirium and 0.73 to 0.83 for incident delirium. All scores performed better than chance but no one score was clearly superior. Conclusions: externally derived delirium risk scores performed well in our independent acute medicine population with reliability unaffected by simplification and might therefore facilitate targeting of multicomponent interventions in routine clinical practice. PMID:26764396

  18. Adrenomedullin for Risk Stratification of Emergency Patients With Nonspecific Complaints

    PubMed Central

    Nickel, Christian Hans; Messmer, Anna Sarah; Ghanim, Leyla; Ilsemann-Karakoumis, Julia; Giersdorf, Sven; Hertel, Sabine; Ernst, Susanne; Geigy, Nicolas; Bingisser, Roland

    2016-01-01

    Abstract Patients with nonspecific complaints (NSC) presenting to the emergency department (ED) are at risk of life-threatening conditions. New stress biomarkers such as the midregional portion of adrenomedullin (MR-proADM) promise to support decision-making. This study tested the following hypotheses: biomarker-assisted disposition of patients with NSC will not increase mortality. Second, discharge from the ED will increase if clinical risk assessment is combined with low MR-proADM levels. Third, inappropriate disposition to a lower level of care will decrease, if clinical assessment is combined with high MR-proADM levels, and fourth that this algorithm is feasible in the ED setting. Prospective, multicenter, randomized, controlled interventional feasibility study with a 30-day follow-up, including patients with NSC. Patients were randomly assigned to either the standard group (decision-making solely based on clinical assessment) or the Novum group (biomarker-assisted). Regarding disposition, patients were assigned to 1 of 3 risk classes: high-risk (admission to hospital), intermediate risk (community geriatric hospital), and low-risk patients (discharge). In the Novum group, in addition to clinical risk assessment, the information of the MR-proADM level was used. Unless there were overruling criteria, patients were transferred or discharged according to the risk assessment. Primary endpoint was 30-day mortality. Secondary endpoints were comparisons of patient disposition and related mortality rates, ED, and hospital length of stay and readmission. The final study cohort consisted of 398 patients (210 in the Standard group and 188 in the Novum group). Overruling, that is, disposition not according to the result of the proposed algorithm occurred in 51 cases. Baseline characteristics between Standard and Novum groups were similar. The mortality rate in the Novum group was 4.3%, as compared to the Standard group mortality of 6.2%, which was not significantly

  19. Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study

    PubMed Central

    Wright, Karen A.; Muir, Kenneth R.; Gavin, Anna

    2016-01-01

    Introduction Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. Methods and Findings Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator

  20. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists.

    PubMed

    Trivedi, Palak J; Corpechot, Christophe; Pares, Albert; Hirschfield, Gideon M

    2016-02-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644-659). PMID:26290473

  1. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists

    PubMed Central

    Trivedi, Palak J.; Corpechot, Christophe; Pares, Albert

    2015-01-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659) PMID:26290473

  2. Effect of carotid atherosclerosis screening on risk stratification during primary cardiovascular disease prevention.

    PubMed

    Bard, Robert L; Kalsi, Henna; Rubenfire, Melvyn; Wakefield, Thomas; Fex, Beverly; Rajagopalan, Sanjay; Brook, Robert D

    2004-04-15

    We investigated the effect that carotid plaque area (CPA) and intima media thickness (IMT) measurements have on risk stratification in 95 patients with intermediate Framingham scores (6% to 19%). The risk status of each patient was adjusted to be low, intermediate, or high based on the results of carotid ultrasound. After carotid testing, 44% (IMT) and 45% (CPA) of the intermediate-risk patients were stratified as low risk, and 22% (IMT) and 40% (CPA) were stratified as high risk. Using the threshold values derived from our laboratory, 28% (IMT) and 45% (CPA) of patients were stratified as low risk, and 35% (IMT) and 27% (CPA) were identified as high risk. These tests adjust the risk strata of >/=63% of patients deemed as having intermediate risk by Framingham scores. PMID:15081449

  3. Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement

    PubMed Central

    Schuetz, Philipp; Huber, Andreas; Müller, Beat; Maisano, Francesco; Taramasso, Maurizio; Moarof, Igal; Obeid, Slayman; Stähli, Barbara E.; Cahenzly, Martin; Binder, Ronald K.; Liebetrau, Christoph; Möllmann, Helge; Kim, Won-Keun; Hamm, Christian; Lüscher, Thomas F.

    2015-01-01

    Background Conventional surgical risk scores lack accuracy in risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR). Elevated levels of midregional proadrenomedullin (MR-proADM) levels are associated with adverse outcome not only in patients with manifest chronic disease states, but also in the general population. Objectives We investigated the predictive value of MR-proADM for mortality in an unselected contemporary TAVR population. Methods We prospectively included 153 patients suffering from severe aortic stenosis who underwent TAVR from September 2013 to August 2014. This population was compared to an external validation cohort of 205 patients with severe aortic stenosis undergoing TAVR. The primary endpoint was all cause mortality. Results During a median follow-up of 258 days, 17 out of 153 patients who underwent TAVR died (11%). Patients with MR-proADM levels above the 75th percentile (≥ 1.3 nmol/l) had higher mortality (31% vs. 4%, HR 8.9, 95% CI 3.0–26.0, P < 0.01), whereas patients with EuroSCORE II scores above the 75th percentile (> 6.8) only showed a trend towards higher mortality (18% vs. 9%, HR 2.1, 95% CI 0.8–5.6, P = 0.13). The Harrell’s C-statistic was 0.58 (95% CI 0.45–0.82) for the EuroSCORE II, and consideration of baseline MR-proADM levels significantly improved discrimination (AUC = 0.84, 95% CI 0.71–0.92, P = 0.01). In bivariate analysis adjusted for EuroSCORE II, MR-proADM levels ≥1.3 nmol/l persisted as an independent predictor of mortality (HR 9.9, 95% CI (3.1–31.3), P <0.01) and improved the model’s net reclassification index (0.89, 95% CI (0.28–1.59). These results were confirmed in the independent validation cohort. Conclusions Our study identified MR-proADM as a novel predictor of mortality in patients undergoing TAVR. In the future, MR-proADM should be added to the commonly used EuroSCORE II for better risk stratification of patients suffering from severe aortic stenosis. PMID

  4. T Wave Alternans And Ventricular Tachyarrhythmia Risk Stratification: A Review

    PubMed Central

    Takagi, Masahiko; Yoshikawa, Junichi

    2003-01-01

    Sudden cardiac death (SCD) is one of the leading causes of mortality in industrialized countries. Thus, identifying patients at high risk of SCD is an important goal. T wave alternans (TWA) is a new method for identifying patients with lethal ventricular tachyarrhythmias, and is dependent on heart rate. The maximal predictive accuracy is achieved at heart rates between 100 and 120 bpm, so that TWA is usually measured during exercise, phamacological stress, or atrial pacing. It has been shown that TWA has high sensitivity and negative predictive value for predicting SCD after myocardial infarction and is also useful for predicting SCD in patients with nonischemic cardiomyopathy. Although the implantable cardioverter defibrillator (ICD) is now the primary therapy for preventing SCD, it is difficult to identify those patients who are susceptible to lethal ventricular tachyarrhythmias for primary prevention. In the prediction of SCD, TWA can be used as a screening test of appropriate patients for further electrophysiological examination and therapy. PMID:16943959

  5. Electrocardiography Patterns and the Role of the Electrocardiography Score for Risk Stratification in Acute Pulmonary Embolism

    PubMed Central

    Ryu, Hyeon Min; Lee, Ju Hwan; Kwon, Yong Seop; Lee, Sang Hyuk; Bae, Myung Hwan; Lee, Jang Hoon; Yang, Dong Heon; Park, Hun Sik; Chae, Shung Chull; Jun, Jae-Eun; Park, Wee-Hyun

    2010-01-01

    Background and Objectives Data on the usefulness of a combination of different electrocardiography (ECG) abnormalities in risk stratification of patients with acute pulmonary embolism (PE) are limited. We thus investigated 12-lead ECG patterns in acute PE to evaluate the role of the ECG score in risk stratification of patients with acute PE. Subjects and Methods One hundred twenty-five consecutive patients (63±14 years, 56 men) with acute PE who were admitted to Kyungpook National University Hospital between November 2001 and January 2008 were included. We analyzed ECG patterns and calculated the ECG score in all patients. We evaluated right ventricular systolic pressure (RVSP) (n=75) and RV hypokinesia (n=80) using echocardiography for risk stratification of acute PE patients. Results Among several ECG findings, sinus tachycardia and inverted T waves in V1-4 (39%) were observed most frequently. The mean ECG score and RVSP were 7.36±6.32 and 49±21 mmHg, respectively. The ECG score correlated with RVSP (r=0.277, p=0.016). The patients were divided into two groups {high ECG-score group (n=38): ECG score >12 and low ECG-score group (n=87): ECG score ≤12} based on the ECG score, with the maximum area under the curve. RV hypokinesia was observed more frequently in the high ECG-score group than in the low ECG-score group (p=0.006). Multivariate analysis revealed that a high ECG score was an independent predictor of high RVSP and RV hypokinesia. Conclusion Sinus tachycardia and inverted T waves in V1-4 were commonly observed in acute PE. Moreover, the ECG score is a useful tool in risk stratification of patients with acute PE. PMID:21088753

  6. Short-term vs. long-term heart rate variability in ischemic cardiomyopathy risk stratification

    PubMed Central

    Voss, Andreas; Schroeder, Rico; Vallverdú, Montserrat; Schulz, Steffen; Cygankiewicz, Iwona; Vázquez, Rafael; Bayés de Luna, Antoni; Caminal, Pere

    2013-01-01

    In industrialized countries with aging populations, heart failure affects 0.3–2% of the general population. The investigation of 24 h-ECG recordings revealed the potential of nonlinear indices of heart rate variability (HRV) for enhanced risk stratification in patients with ischemic heart failure (IHF). However, long-term analyses are time-consuming, expensive, and delay the initial diagnosis. The objective of this study was to investigate whether 30 min short-term HRV analysis is sufficient for comparable risk stratification in IHF in comparison to 24 h-HRV analysis. From 256 IHF patients [221 at low risk (IHFLR) and 35 at high risk (IHFHR)] (a) 24 h beat-to-beat time series (b) the first 30 min segment (c) the 30 min most stationary day segment and (d) the 30 min most stationary night segment were investigated. We calculated linear (time and frequency domain) and nonlinear HRV analysis indices. Optimal parameter sets for risk stratification in IHF were determined for 24 h and for each 30 min segment by applying discriminant analysis on significant clinical and non-clinical indices. Long- and short-term HRV indices from frequency domain and particularly from nonlinear dynamics revealed high univariate significances (p < 0.01) discriminating between IHFLR and IHFHR. For multivariate risk stratification, optimal mixed parameter sets consisting of 5 indices (clinical and nonlinear) achieved 80.4% AUC (area under the curve of receiver operating characteristics) from 24 h HRV analysis, 84.3% AUC from first 30 min, 82.2 % AUC from daytime 30 min and 81.7% AUC from nighttime 30 min. The optimal parameter set obtained from the first 30 min showed nearly the same classification power when compared to the optimal 24 h-parameter set. As results from stationary daytime and nighttime, 30 min segments indicate that short-term analyses of 30 min may provide at least a comparable risk stratification power in IHF in comparison to a 24 h analysis period. PMID:24379785

  7. Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

    SciTech Connect

    Huang Jiayi; Vicini, Frank A.; Williams, Scott G.; Ye Hong; McGrath, Samuel; Ghilezan, Mihai; Krauss, Daniel; Martinez, Alvaro A.; Kestin, Larry L.

    2012-07-15

    Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleason score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National

  8. Proposals for enhanced health risk assessment and stratification in an integrated care scenario

    PubMed Central

    Dueñas-Espín, Ivan; Vela, Emili; Pauws, Steffen; Bescos, Cristina; Cano, Isaac; Cleries, Montserrat; Contel, Joan Carles; de Manuel Keenoy, Esteban; Garcia-Aymerich, Judith; Gomez-Cabrero, David; Kaye, Rachelle; Lahr, Maarten M H; Lluch-Ariet, Magí; Moharra, Montserrat; Monterde, David; Mora, Joana; Nalin, Marco; Pavlickova, Andrea; Piera, Jordi; Ponce, Sara; Santaeugenia, Sebastià; Schonenberg, Helen; Störk, Stefan; Tegner, Jesper; Velickovski, Filip; Westerteicher, Christoph; Roca, Josep

    2016-01-01

    Objectives Population-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario. Settings The five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL). Participants Responsible teams for regional data management in the five ACT regions. Primary and secondary outcome measures We characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction. Results There was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment. Conclusions The results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches

  9. A Model for Opioid Risk Stratification: Assessing the Psychosocial Components of Orofacial Pain.

    PubMed

    Kulich, Ronald J; Backstrom, Jordan; Brownstein, Jennifer; Finkelman, Matthew; Dhadwal, Shuchi; DiBennedetto, David

    2016-08-01

    This article describes a model of opiate risk stratification with a special focus on dentistry and oral surgery. A brief overview covers the scope of the US opioid abuse and misuse epidemic, and the role of the dentist in mitigating the problems of diversion and misuse of controlled substances. The expanding role of dentistry is summarized. An assessment outlines gathering critical risk information, screening questionnaires, access to state prescription monitoring programs, and communication with cotreating providers. Special populations are discussed. Barriers and possible solutions for effective implementation of these strategies are summarized. PMID:27475506

  10. Diabetes Mellitus and Prediabetes on Kidney Transplant Waiting List- Prevalence, Metabolic Phenotyping and Risk Stratification Approach

    PubMed Central

    Guthoff, Martina; Vosseler, Dorothea; Langanke, Julia; Nadalin, Silvio; Königsrainer, Alfred; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2015-01-01

    Background Despite a significant prognostic impact, little is known about disturbances in glucose metabolism among kidney transplant candidates. We assess the prevalence of diabetes mellitus (DM) and prediabetes on kidney transplant waiting list, its underlying pathophysiology and propose an approach for individual risk stratification. Methods All patients on active kidney transplant waiting list of a large European university hospital transplant center were metabolically phenotyped. Results Of 138 patients, 76 (55%) had disturbances in glucose metabolism. 22% of patients had known DM, 3% were newly diagnosed. 30% were detected to have prediabetes. Insulin sensitivity and-secretion indices allowed for identification of underlying pathophysiology and risk factors. Age independently affected insulin secretion, resulting in a relative risk for prediabetes of 2.95 (95%CI 1.38–4.83) with a cut-off at 48 years. Body mass index independently affected insulin sensitivity as a continuous variable. Conclusions The prevalence of DM or prediabetes on kidney transplant waiting list is as high as 55%, with more than one third of patients previously undiagnosed. Oral glucose tolerance test is mandatory to detect all patients at risk. Metabolic phenotyping allows for differentiation of underlying pathophysiology and provides a basis for early individual risk stratification and specific intervention to improve patient and allograft outcome. PMID:26398489

  11. Isoniazid-induced polyneuropathy in a tuberculosis patient – implication for individual risk stratification with genotyping?

    PubMed Central

    Stettner, Mark; Steinberger, Daniela; Hartmann, Christian J; Pabst, Tatjana; Konta, Lidija; Hartung, Hans Peter; Kieseier, Bernd C

    2015-01-01

    Background Development of polyneuropathy (PNP) under treatment for tuberculosis (TB), including isoniazid (INH), is a highly relevant adverse drug effect. The NAT2 acetylation status is a predictor of potential toxic effects of INH. The question as to whether individual risk stratification by genotyping is useful to avoid suffering of patients and to lower costs for the health care system is of considerable clinical importance. Case Presentation After drug treatment for TB, including INH, a 23-year-old man developed severe PNP. During the treatment, laboratory results have been indicating incipient liver and renal injury. Later, molecular genetic analyses were performed and revealed a variation in the NAT2 gene and the c1/c2 genotype of the CYP2E1 gene, both described to contribute to an elevated risk for anti-tuberculostatic-induced liver damages (ATIL). Conclusion The combination of metabolizer genotypes should be taken into account as a cause for toxic effects and the development of PNP. Individual genotyping, performed before medication or at least if an elevation of liver parameters is observed, may reduce the risk of severe cases of PNP by early adjustment of treatment. Our case study indicates that evaluation of individual risk stratification with systematic pharmacogenetic genotyping of metabolizer gene combinations in the context of TB treatment should be addressed in clinical studies with larger cohorts. PMID:26355945

  12. Bleeding risk stratification in an era of aggressive management of acute coronary syndromes

    PubMed Central

    Abu-Assi, Emad; Raposeiras-Roubín, Sergio; García-Acuña, José María; González-Juanatey, José Ramón

    2014-01-01

    Major bleeding is currently one of the most common non-cardiac complications observed in the treatment of patients with acute coronary syndrome (ACS). Hemorrhagic complications occur with a frequency of 1% to 10% during treatment for ACS. In fact, bleeding events are the most common extrinsic complication associated with ACS therapy. The identification of clinical characteristics and particularities of the antithrombin therapy associated with an increased risk of hemorrhagic complications would make it possible to adopt prevention strategies, especially among those exposed to greater risk. The international societies of cardiology renewed emphasis on bleeding risk stratification in order to decide strategy and therapy for patients with ACS. With this review, we performed an update about the ACS bleeding risk scores most frequently used in daily clinical practice. PMID:25429326

  13. Stratification of the Risk of Sudden Death in Nonischemic Heart Failure

    PubMed Central

    Pimentel, Maurício; Zimerman, Leandro Ioschpe; Rohde, Luis Eduardo

    2014-01-01

    Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure. PMID:25352509

  14. Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

    PubMed Central

    Ciampi, Quirino; Villari, Bruno

    2007-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Echocardiography represents the "gold standard" in the assessment of LV systolic dysfunction and in the recognition of systolic heart failure, since dilatation of the LV results in alteration of intracardiac geometry and hemodynamics leading to increased morbidity and mortality. The functional mitral regurgitation is a consequence of adverse LV remodelling that occurs with a structurally normal valve and it is a marker of adverse prognosis. Diastolic dysfunction plays a major role in signs and symptoms of HF and in the risk stratification, and provides prognostic information independently in HF patients and impaired systolic function. Ultrasound lung comets are a simple echographic sign of extravascular lung water, more frequently associated with left ventricular diastolic and/or systolic dysfunction, which can integrate the clinical and pathophysiological information provided by conventional echocardiography and provide a useful information for prognostic stratification of HF patients. Contractile reserve is defined as the difference between values of an index of left ventricular contractility during peak stress and its baseline values and the presence of myocardial viability predicts a favorable outcome. A non-invasive echocardiographic method for the evaluation of force-frequency relationship has been proposed to assess the changes in contractility during stress echo. In conclusion, in HF patients, the evaluation of systolic, diastolic function and myocardial contractile reserve plays a fundamental role in the risk stratification. The highest risk is present in HF patients with a heart that is weak, big, noisy, stiff and wet. PMID:17910744

  15. Clinical Usefulness of Novel Serum and Imaging Biomarkers in Risk Stratification of Patients with Stable Angina

    PubMed Central

    Ikonomidis, Ignatios; Tsantes, Argirios

    2014-01-01

    Inflammatory mediators appear to be the most intriguing yet confusing subject, regarding the management of patients with acute coronary syndromes (ACS). The current inflammatory concept of atherosclerotic coronary artery disease (CAD) led many investigators to concentrate on systemic markers of inflammation, as well as imaging techniques, which may be helpful in risk stratification and prognosis assessment for cardiovascular events. In this review, we try to depict many of the recently studied markers regarding stable angina (SA), their clinical usefulness, and possible future applications in the field. PMID:25045198

  16. Value of planar 201Tl imaging in risk stratification of patients recovering from acute myocardial infarction

    SciTech Connect

    Gibson, R.S.; Watson, D.D. )

    1991-09-01

    Although exercise ECG testing has been shown to have important prognostic value after acute myocardial infarction, exercise 201Tl scintigraphy offers several potential advantages, including: (1) increased sensitivity for detecting residual myocardial ischemia; (2) the ability to localize ischemia to a specific area or areas subtended by a specific coronary artery; (3) the ability to identify exercise-induced left ventricular dysfunction, which is manifested by increased lung uptake or transient left ventricular dilation; and (4) more reliable risk stratification of individual patients. The more optimal prognostic efficiency of 201Tl scintigraphy partially results from the fact that the error rate in falsely classifying patients as low risk is significantly smaller with 201Tl scintigraphy than with stress ECG. Because of these substantial advantages, there seems to be adequate rationale for recommending exercise perfusion imaging rather than exercise ECG alone as the preferred method for evaluating mortality and morbidity risks after acute myocardial infarction.

  17. Coronary Artery Calcium Screening: Does it Perform Better than Other Cardiovascular Risk Stratification Tools?

    PubMed Central

    Zeb, Irfan; Budoff, Matthew

    2015-01-01

    Coronary artery calcium (CAC) has been advocated as one of the strongest cardiovascular risk prediction markers. It performs better across a wide range of Framingham risk categories (6%–10% and 10%–20% 10-year risk categories) and also helps in reclassifying the risk of these subjects into either higher or lower risk categories based on CAC scores. It also performs better among population subgroups where Framingham risk score does not perform well, especially young subjects, women, family history of premature coronary artery disease and ethnic differences in coronary risk. The absence of CAC is also associated with excellent prognosis, with 10-year event rate of 1%. Studies have also compared with other commonly used markers of cardiovascular disease risk such as Carotid intima-media thickness and highly sensitive C-reactive protein. CAC also performs better compared with carotid intima-media thickness and highly sensitive C-reactive protein in prediction of coronary heart disease and cardiovascular disease events. CAC scans are associated with relatively low radiation exposure (0.9–1.1 mSv) and provide information that can be used not only for risk stratification but also can be used to track the progression of atherosclerosis and the effects of statins. PMID:25807266

  18. Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism

    PubMed Central

    Bĕlohlávek, Jan; Dytrych, Vladimír; Linhart, Aleš

    2013-01-01

    Pulmonary embolism is an important clinical entity with considerable mortality despite advances in diagnosis and treatment. In the present article, the authors offer a comprehensive review focused mainly on epidemiology, risk factors, risk stratification, pathophysiological considerations and clinical presentation. Diagnosis based on assessment of clinical likelihood, electrocardiography, chest x-ray, D-dimer levels, markers of myocardial injury and overload, and blood gases is discussed in detail. Special attention is devoted to the clinical use of computed tomography, pulmonary angiography and echocardiography in the setting of pulmonary embolism. PMID:23940438

  19. Risk stratification-based surveillance of bacterial contamination in metropolitan ambulances.

    PubMed

    Noh, Hyun; Shin, Sang Do; Kim, Nam Joong; Ro, Young Sun; Oh, Hyang Soon; Joo, Se Ik; Kim, Jung In; Ong, Marcus Eng Hock

    2011-01-01

    We aimed to know the risk-stratification-based prevalence of bacterial contamination of ambulance vehicle surfaces, equipment, and materials. This study was performed in a metropolitan area with fire-based single-tiered Basic Life Support ambulances. Total 13 out of 117 ambulances (11.1%) were sampled and 33 sites per each ambulance were sampled using a soft rayon swab and aseptic containers. These samples were then plated onto a screening media of blood agar and MacConkey agar. Specific identification with antibiotic susceptibility was performed. We categorized sampling sites into risk stratification-based groups (Critical, Semi-critical, and Non-critical equipment) related to the likelihood of direct contact with patients' mucosa. Total 214 of 429 samples showed positive results (49.9%) for any bacteria. Four of these were pathogenic (0.9%) (MRSA, MRCoNS, and K. pneumoniae), and 210 of these were environmental flora (49.0%). However, the prevalence (positive/number of sample) of bacterial contamination in critical, semi-critical airway, semi-critical breathing apparatus group was as high as 15.4% (4/26), 30.7% (16/52), and 46.2% (48/104), respectively. Despite current formal guidelines, critical and semi-critical equipments were contaminated with pathogens and normal flora. This study suggests the need for strict infection control and prevention for ambulance services. PMID:21218040

  20. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.

    PubMed

    Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Bailey, Simon; Clifford, Steven C; Doz, Francois; Kool, Marcel; Dufour, Christelle; Vassal, Gilles; Milde, Till; Witt, Olaf; von Hoff, Katja; Pietsch, Torsten; Northcott, Paul A; Gajjar, Amar; Robinson, Giles W; Padovani, Laetitia; André, Nicolas; Massimino, Maura; Pizer, Barry; Packer, Roger; Rutkowski, Stefan; Pfister, Stefan M; Taylor, Michael D; Pomeroy, Scott L

    2016-06-01

    Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3-17). Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90 % survival), average (standard) risk (75-90 % survival), high risk (50-75 % survival) and very high risk (<50 % survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently

  1. The value of exercise radionuclide ventriculography in risk stratification after coronary arterial bypass grafting

    SciTech Connect

    Iskandrian, A.S.; Hakki, A.H.; Goel, I.P.; Mundth, E.D.; Kane, S.; Schenk, C.

    1985-05-01

    Cardiac events after coronary artery bypass surgery (CABG) may be related to left ventricular (LV) function, residual coronary artery diseases (CAD), graft occlusion, and progression of CAD. This study examined the value of rest and exercise (EX) radionuclide ventriculography (RNV) done 3-6 mos after CABG in risk stratification in 212 pts. There were 185 men and 27 women, aged 57 +- 8 years (mean +- SD). During a followup period of up to 4 years, (15 +- 10 months), there were 23 cardiac events; 13 pts died of cardiac causes and 20 had non-fatal acute myocardial infarctions. The pts with and without events did not differ in: clinical presentation after CABG (most were asymptomatic), medications and ECG findings at rest and EX. The pts with events had lower EX systolic blood pressure (p < 0.01); resting LV ejection fraction (EF) (p = 0.002), and EX EF (40 +- 18% vs 54 +- 16%, p = 0.002). The change in EF (rest to EX) was not significantly different (l.6 +- 8.2%, vs 2.1 +- 9.2%). Survival analysis (Cox model) identified the EX EF as the best predictor of death and total events (X/sup 2/ = 4.3 and 2.4, p = 0.04 and 0.07 respectively). Actuarial life table analysis showed that the risk increased as the EX EF decreased when pts were grouped into EX EF greater than or equal to 50, 30-49, and <30%, (p < 0.001, Mantel-Cox). Thus, EX RNA is useful in risk stratification after CABG. The EX LVEF is an important descriptor that categorizes pts into different risks groups. The pts at high risk probably require more aggressive followup and continued medical therapy.

  2. Molecular microscope strategy to improve risk stratification in early antibody-mediated kidney allograft rejection.

    PubMed

    Loupy, Alexandre; Lefaucheur, Carmen; Vernerey, Dewi; Chang, Jessica; Hidalgo, Luis G; Beuscart, Thibaut; Verine, Jerome; Aubert, Olivier; Dubleumortier, Sébastien; Duong van Huyen, Jean-Paul; Jouven, Xavier; Glotz, Denis; Legendre, Christophe; Halloran, Philip F

    2014-10-01

    Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant. In addition to conventional features, we assessed microarray-based gene expression in transplant biopsy specimens using relevant molecular measurements: the ABMR Molecular Score and endothelial donor-specific antibody-selective transcript set. The main outcomes were kidney transplant loss and progression to chronic transplant injury. We identified 74 patients with ABMR in the principal cohort and 54 patients with ABMR in the validation cohort. Conventional features independently associated with failure were donor age and humoral histologic score (g+ptc+v+cg+C4d). Adjusting for conventional features, ABMR Molecular Score (hazard ratio [HR], 2.22; 95% confidence interval [95% CI], 1.37 to 3.58; P=0.001) and endothelial donor-specific antibody-selective transcripts (HR, 3.02; 95% CI, 1.00 to 9.16; P<0.05) independently associated with an increased risk of graft loss. The results were replicated in the independent validation group. Adding a gene expression assessment to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 1.01; 95% CI, 0.57 to 1.46; P<0.001; integrated discrimination improvement, 0.16; P<0.001). Compared with conventional assessment, the addition of gene expression measurement in kidney transplants with ABMR improves stratification of patients at high risk for graft loss. PMID:24700874

  3. Tools for risk stratification of sudden cardiac death: A review of the literature in different patient populations

    PubMed Central

    Ragupathi, Loheetha; Pavri, Behzad B.

    2014-01-01

    While various modalities to determine risk of sudden cardiac death (SCD) have been reported in clinical studies, currently reduced left ventricular ejection fraction remains the cornerstone of SCD risk stratification. However, the absolute burden of SCD is greatest amongst populations without known cardiac disease. In this review, we summarize the evidence behind current guidelines for implantable cardioverter defibrillator (ICD) use for the prevention of SCD in patients with ischemic heart disease (IHD). We also evaluate the evidence for risk stratification tools beyond clinical guidelines in the general population, patients with IHD, and patients with other known or suspected medical conditions. PMID:24568833

  4. Risk Stratification for Sudden Cardiac Death In Patients With Non-ischemic Dilated Cardiomyopathy

    PubMed Central

    Shekha, Karthik; Ghosh, Joydeep; Thekkoott, Deepak; Greenberg, Yisachar

    2005-01-01

    Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge .Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice. PMID:16943952

  5. Rockall score for risk stratification in adult patients with non-variceal upper gastrointestinal hemorrhage.

    PubMed

    Rahman, M W; Sumon, S M; Amin, M R; Kahhar, M A

    2013-10-01

    The Rockall risk score is a simple, validated predictive index that may serve as a useful clinical decision for assessing the risk of subsequent adverse outcomes in patients with non-variceal upper gastrointestinal hemorrhage (UGIH). The observational study was carried out over a period of 6 months from 10th July, 2012 to 09th January, 2013 in Department of Medicine, Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 60 patients with non-variceal UGIH were taken for the study during study period to see risk stratification by Rockall score and short term hospital outcome in non-variceal upper GI hemorrhage patients. Categorical variables were reported as percentage and Means and proportions were carried out using the Chi-square test of different variables. Among study population age distribution were 42(70%) <60 years, 16(26.7%) from 60-79 years and 02(3.3%) 80 years or above and sex distribution were 39(65%) male and 21(35%) were female patients. Rockall score of patients 11(18.3%) had score 1, 6(10%) had score 2, 13(21.7%) had score 3, 10(16.7%) had score 4, 6(10%) had score 5, 6(10%) had score 6, 4(6.7%) had score 7, 3(5.0%) had score 8 and 1(1.7%) had score 9. Risk stratification showed 30(50%) had low risk (score 3 or <3), 26(43.3%) had moderate risk (score 4-7) and 4(6.7%) had high risk (score 8 or >8). Outcome after initial Rockall scoring and endoscopy were found that 7(11.7%) died, 46(76.6%) survived and 7(11.7%) patients survived with complication. This study showed that Rockall score of ≤3 was predictive of low risk of adverse outcomes, and a score of ≥8 was predictive of high mortality and was useful in identifying patients with non-variceal UGIH who had low-risk scores in order to triage appropriately, without affecting patient outcomes. PMID:24292298

  6. Risk Stratification in Older Patients With Acute Myocardial Infarction: Physicians' Perspectives

    PubMed Central

    Feder, Shelli L.; Schulman-Green, Dena; Dodson, John A.; Geda, Mary; Williams, Kathleen; Nanna, Michael G.; Allore, Heather G.; Murphy, Terrence E.; Tinetti, Mary E.; Gill, Thomas M.; Chaudhry, Sarwat I.

    2016-01-01

    Objective Risk stratification models support clinical decision making in acute myocardial infarction (AMI) care. Existing models were developed using data from younger populations, potentially limiting accuracy and relevance in older adults. We describe physician-perceived risk factors, views of existing models, and preferences for future model development in older adults. Method Qualitative study using semi-structured telephone interviews and the constant comparative method. Results Twenty-two physicians from 14 institutions completed the interviews. Median age was 37, and median years of clinical experience was 11.5. Perceived predictors included cardiovascular, comorbid, functional, and social risk factors. Physicians viewed models as easy to use, yet neither inclusive of risk factors nor predictive of non-mortality outcomes germane to clinical decision making in older adults. Ideal models included multidimensional risk domains and operational requirements. Discussion Physicians reported limitations of available risk models when applied to older adults with AMI. New models are needed to guide AMI treatment in this population. PMID:26100619

  7. Caprini Scores, Risk Stratification, and Rivaroxaban in Plastic Surgery: Time to Reconsider Our Strategy

    PubMed Central

    2016-01-01

    Summary: Limited data are available regarding the pathophysiology of venous thromboembolism in plastic surgery patients. In an effort to identify patients at greater risk, some investigators promote individual risk assessment using Caprini scores. However, these scores do not correlate with relative risk values. Affected patients cannot be reliably predicted (97% false positive rate). Caprini scores make many body contouring patients candidates for chemoprophylaxis, an intervention that introduces risks related to anticoagulation. Caprini has financial conflicts with several companies that manufacture products such as enoxaparin, commonly used for chemoprophylaxis. Rivaroxaban, taken orally, has been used by some plastic surgeons as an alternative to enoxaparin injections. However, this medication is not United States Food and Drug Administration approved for venous thromboembolism prophylaxis in plastic surgery patients, and a reversal agent is unavailable. This article challenges the prevailing wisdom regarding individual risk stratification and chemoprophylaxis. Alternative methods to reduce risk for all patients include safer anesthesia methods and Doppler ultrasound surveillance. Clinical findings alone are unreliable in diagnosing deep venous thromboses. Only by using a reliable diagnostic tool such as Doppler ultrasound are we able to learn more about the natural history of this problem in our patients. Such knowledge is likely to better inform our treatment recommendations. PMID:27482481

  8. Caprini Scores, Risk Stratification, and Rivaroxaban in Plastic Surgery: Time to Reconsider Our Strategy.

    PubMed

    Swanson, Eric

    2016-06-01

    Limited data are available regarding the pathophysiology of venous thromboembolism in plastic surgery patients. In an effort to identify patients at greater risk, some investigators promote individual risk assessment using Caprini scores. However, these scores do not correlate with relative risk values. Affected patients cannot be reliably predicted (97% false positive rate). Caprini scores make many body contouring patients candidates for chemoprophylaxis, an intervention that introduces risks related to anticoagulation. Caprini has financial conflicts with several companies that manufacture products such as enoxaparin, commonly used for chemoprophylaxis. Rivaroxaban, taken orally, has been used by some plastic surgeons as an alternative to enoxaparin injections. However, this medication is not United States Food and Drug Administration approved for venous thromboembolism prophylaxis in plastic surgery patients, and a reversal agent is unavailable. This article challenges the prevailing wisdom regarding individual risk stratification and chemoprophylaxis. Alternative methods to reduce risk for all patients include safer anesthesia methods and Doppler ultrasound surveillance. Clinical findings alone are unreliable in diagnosing deep venous thromboses. Only by using a reliable diagnostic tool such as Doppler ultrasound are we able to learn more about the natural history of this problem in our patients. Such knowledge is likely to better inform our treatment recommendations. PMID:27482481

  9. Development of Inpatient Risk Stratification Models of Acute Kidney Injury for Use in Electronic Health Records

    PubMed Central

    Matheny, Michael E.; Miller, Randolph A.; Ikizler, T. Alp; Waitman, Lemuel R.; Denny, Joshua C.; Schildcrout, Jonathan S.; Dittus, Robert S.; Peterson, Josh F.

    2016-01-01

    Objective Patients with hospital-acquired acute kidney injury (AKI) are at risk for increased mortality and further medical complications. Evaluating these patients with a prediction tool easily implemented within an electronic health record (EHR) would identify high risk patients prior to the development of AKI, and could prevent iatrogenically induced episodes of AKI and improve clinical management. Methods We used structured clinical data acquired from an EHR to identify patients with normal kidney function for admissions from August 1st, 1999 to July 31st, 2003. Using administrative, computerized provider order entry, and laboratory test data, we developed a 3-level risk stratification model to predict each of two severity levels of in-hospital AKI as defined by RIFLE criteria. The severity levels were defined as 150% or 200% of baseline serum creatinine. Model discrimination and calibration was evaluated using 10-fold cross-validation. Results Cross-validation of the models resulted in area under the receiver operating characteristic (AUC) curves of 0.75 (150% elevation) and 0.78 (200% elevation). Both models were adequately calibrated as measured by the Hosmer-Lemeshow goodness-of-fit test chi-squared values of 9.7 (p = 0.29) and 12.7 (p = 0.12), respectively. Conclusions We generated risk prediction models for hospital-acquired AKI using only commonly available electronic data. The models identify patients at high risk for AKI who might benefit from early intervention or increased monitoring. PMID:20354229

  10. Post-operative bleeding risk stratification in cardiac pulmonary bypass patients using artificial neural network.

    PubMed

    Huang, Richard S P; Nedelcu, Elena; Bai, Yu; Wahed, Amer; Klein, Kimberly; Tint, Hlaing; Gregoric, Igor; Patel, Manish; Kar, Biswajit; Loyalka, Pranav; Nathan, Sriram; Radovancevic, Rajko; Nguyen, Andy N D

    2015-01-01

    The prediction of bleeding risk in cardiopulmonary bypass (CPB) patients plays a vital role in their postoperative management. Therefore, an artificial neural network (ANN) to analyze intra-operative laboratory data to predict postoperative bleeding was set up. The JustNN software (Neural Planner Software, Cheshire, England) was used. This ANN was trained using 15 intra-operative laboratory parameters paired with one output category - risk of bleeding, defined as units of blood components transfused in 48 hours. The ANN was trained with the first 39 CPB cases. The set of input parameters for this ANN was also determined, and the ANN was validated with the next 13 cases. The set of input parameters include five components: pro-thrombin time, platelet count, thromboelastograph-reaction time, D-Dimer, and thromboelastograph-coagulation index. The validation results show 9 cases (69.2%) with exact match, 3 cases (23.1%) with one-grading difference, and 1 case (7.7%) with two-grading difference between actual blood usage versus predicted blood usage. To the best of our knowledge, ours is the first ANN developed for post-operative bleeding risk stratification of CPB patients. With promising results, we have started using this ANN to risk-stratify our CPB patients, and it has assisted us in predicting post-operative bleeding risk. PMID:25887872

  11. Perioperative risk stratification for a patient with severe obstructive sleep apnoea undergoing laparoscopic banding surgery.

    PubMed

    Weinberg, Laurence; Tay, Stan; Lai, Chung Fei; Barnes, Maree

    2013-01-01

    Despite the increasing prevalence of obstructive sleep apnoea (OSA), there is limited evidence to guide appropriate preoperative investigations, inpatient or outpatient surgery allocation, and the anticipated level of postoperative care. With reference to our institution's perioperative risk stratification, we describe the case of a 46-year-old Caucasian male with a body mass index of 51 kg/m(2) admitted for laparoscopic band insertion. Management based on our guidelines involved a preoperative polysomnography where the patient was confirmed to have severe OSA. His postoperative care was then managed in the high dependency care unit. He was discharged home on day 2 with no further sequelae. We provide evidence that adoption of this model of care can simplify clinical decision making and resource allocation with favourable patient outcomes. PMID:23370960

  12. Future directions in risk stratification and therapy for advanced pediatric genitourinary rhabdomyosarcoma.

    PubMed

    Harel, Miriam; Ferrer, Fernando A; Shapiro, Linda H; Makari, John H

    2016-02-01

    Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in infants and children and the third most common pediatric solid tumor, accounting for 5% to 15% of all childhood solid tumors. Of these, 15% to 20% arise from the genitourinary tract, with the most common sites originating from the prostate, bladder, and paratesticular regions, followed by the vagina and uterus. Although upfront radical surgery was used at the initiation of Intergroup RMS Study-I (1972-1978), the treatment paradigm has shifted to include initial biopsy with the goal of organ preservation, systemic chemotherapy for all patients, and local control involving surgical resection with or without radiation therapy for most patients. Collaborative group clinical trials have led to dramatic improvement in survival rates from 1960 to 1996 among patients with low- or intermediate-risk disease; however, outcomes appear to have plateaued in more recent years, and the prognosis for patients with metastatic or relapsed/refractory disease remains poor. Current management goals include minimizing toxicity while maintaining the excellent outcomes in low-risk disease, as well as improving outcomes in patients with intermediate- and high-risk disease. Advances in genetic analysis have allowed further refinement in risk stratification of patients. Perhaps the most significant recent development in RMS research was the discovery of an association of alveolar RMS (ARMS) with translocations t(2;13) and t(1;13). Translocation fusion-positive tumors comprise 80% of ARMS and are more aggressive. Fusion-negative ARMS may have a clinical course similar to embryonal RMS. Future Children's Oncology Group sarcoma studies will likely incorporate fusion status into risk stratification and treatment allocation. Newer radiotherapy modalities hold promise for providing local control of disease while minimizing morbidity. The addition of traditional cytotoxic chemotherapeutic agents does not seem to improve

  13. Preoperative risk stratification models fail to predict hospital cost of cardiac surgery patients

    PubMed Central

    2013-01-01

    Background Preoperative risk stratification models have previously been suggested to predict cardiac surgery unit costs. However, there is a lack of consistency in their reliability in this field. In this study we aim to test the correlation between the values of six commonly known preoperative scoring systems and evaluate their reliability at predicting unit costs of cardiac surgery patients. Methods Over a period of 14 months all consecutive adult patients undergoing cardiac surgery on cardiopulmonary bypass were prospectively classified using six preoperative scoring models (EuroSCORE, Parsonnet, Ontario, French, Pons and CABDEAL). Transplantation patients were the only patients we excluded. Total hospital costs for each patient were calculated independently on a daily basis using the bottom up method. The full unit costs were calculated including preoperative diagnostic tests, operating room cost, disposable materials, drugs, blood components as well as costs for personnel and fixed hospital costs. The correlation between hospital cost and the six models was determined by linear regression analysis. Both Spearman’s and Pearson’s correlation coefficients were calculated from the regression lines. An analysis of residuals was performed to determine the quality of the regression. Results A total of 887 patients were operated on for CABG (n = 608), valve (n = 142), CABG plus valve (n = 100), thoracic aorta (n = 33) and ventricular assist devices (n = 4). Mean age of the patients was 68.3±9.9 years, 27.6% were female. 30-day mortality rate was 4.1%. Correlation between the six models and hospital cost was weak (Pearson’s: r < 0.30; Spearman’s: r < 0.40). Conclusion The risk stratification models in this study are not reliable at predicting total costs of cardiac surgical patients. We therefore do not recommend their use for this purpose. PMID:23659251

  14. Orthostatic Blood Pressure Test for Risk Stratification in Patients with Hypertrophic Cardiomyopathy

    PubMed Central

    Münch, Julia; Aydin, Ali; Suling, Anna; Voigt, Christian; Blankenberg, Stefan; Patten, Monica

    2015-01-01

    Background Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in young adults, mainly ascribed to ventricular tachycardia (VT). Assuming that VT is the major cause of (pre-) syncope in HCM patients, its occurrence is essential for SCD risk stratification and primarily preventive ICD-implantation. However, evidence of VT during syncope is often missing. As the differentiation of potential lethal causes for syncope such as VT from more harmless reasons is crucial, HCM patients were screened for orthostatic dysregulation by using a simple orthostatic blood pressure test. Methods Over 15 months (IQR [9;20]) 100 HCM patients (55.8±16.2 yrs, 61% male) were evaluated for (pre-)syncope and VT (24h-ECGs, device-memories) within the last five years. Eighty patients underwent an orthostatic blood pressure test. Logistic regression models were used for statistical analysis. Results In older patients (>40 yrs) a positive orthostatic test result increased the chance of (pre-) syncope by a factor of 63 (95%-CI [8.8; 447.9], p<0.001; 93% sensitivity, 95%-CI [76; 99]; 74% specificity, 95%-CI [58; 86]). No correlation with VT was shown. A prolonged QTc interval also increased the chance of (pre-) syncope by a factor of 6.6 (95%-CI [2.0; 21.7]; p=0.002). Conclusions The orthostatic blood pressure test is highly valuable for evaluation of syncope and presyncope especially in older HCM patients, suggesting that orthostatic syncope might be more relevant than previously assumed. Considering the high complication rates due to ICD therapies, this test may provide useful information for the evaluation of syncope in individual risk stratification and may help to prevent unnecessary device implantations, especially in older HCM patients. PMID:26107635

  15. Heart rate variability and non-linear dynamics in risk stratification.

    PubMed

    Perkiömäki, Juha S

    2011-01-01

    The time-domain measures and power-spectral analysis of heart rate variability (HRV) are classic conventional methods to assess the complex regulatory system between autonomic nervous system and heart rate and are most widely used. There are abundant scientific data about the prognostic significance of the conventional measurements of HRV in patients with various conditions, particularly with myocardial infarction. Some studies have suggested that some newer measures describing non-linear dynamics of heart rate, such as fractal measures, may reveal prognostic information beyond that obtained by the conventional measures of HRV. An ideal risk indicator could specifically predict sudden arrhythmic death as the implantable cardioverter-defibrillator (ICD) therapy can prevent such events. There are numerically more sudden deaths among post-infarction patients with better preserved left ventricular function than in those with severe left ventricular dysfunction. Recent data support the concept that HRV measurements, when analyzed several weeks after acute myocardial infarction, predict life-threatening ventricular tachyarrhythmias in patients with moderately depressed left ventricular function. However, well-designed prospective randomized studies are needed to evaluate whether the ICD therapy based on the assessment of HRV alone or with other risk indicators improves the patients' prognosis. Several issues, such as the optimal target population, optimal timing of HRV measurements, optimal methods of HRV analysis, and optimal cutpoints for different HRV parameters, need clarification before the HRV analysis can be a widespread clinical tool in risk stratification. PMID:22084633

  16. Multiscale regularity analysis of the Heart Rate Variability: stratification of cardiac death risk.

    PubMed

    Valencia, J F; Vallverdú, M; Cygankiewicz, I; Voss, A; Vazquez, R; de Luna, A Bayés; Caminal, P

    2007-01-01

    Subjects with ischemic dilated cardiomiopathy tend to suffer episodes of sudden cardiac death, thus risk stratification is essential to establish an adequate therapy for the patients. In this work, a new methodology was proposed for the study of the heart rate variability by using a multiscale analysis based on the concept of entropy rates, for improving risk prediction in cardiac patients. Symbolic dynamics were applied to RR time series and sets of words in several scales were constructed. The multiscale regularity analysis was proposed by comparing the entropies, calculated using Shannon and Renyi definitions, of the series of words in different scales. The study considered the selection of the best parameters for the length of the words (l) and the order of the entropies (q). Statistical analysis with repeated measures and discriminant analysis revealed statistically significant differences (p-value<0.05) and a high percentage of well classified subjects in their different risk groups, with sensitivity, specificity and positive predictive values of 100%. PMID:18003368

  17. Stress testing for risk stratification of patients with low to moderate probability of acute cardiac ischemia.

    PubMed

    Chandra, A; Rudraiah, L; Zalenski, R J

    2001-02-01

    In summary, this article focused on the use of stress testing to risk-stratify patients at the conclusion of their emergency evaluation for ACI. As discussed, those patients in the probably not ACI category require additional risk stratification prior to discharge. It should be kept in mind that patients in this category are heterogeneous, containing subgroups at both higher and lower risk of ACI and cardiac events. The patients with lower pretest probability for ACI may only need exercise testing in the ED. Patients with higher pretest probability should undergo myocardial perfusion or echocardiographic stress testing to maximize diagnostic and prognostic information. Prognostic information is the key to provocative testing in the ED. Prognostic information is the component that will help emergency physicians identify the patients who may be discharged home safely without having to worry about a 6% annual cardiac death rate and a 10% overall death rate over the next 30 months. Stress testing provides this key prognostic data, and it can be obtained in short-stay chest pain observation units in a safe, timely, and cost-effective fashion. PMID:11214405

  18. Risk stratification of non-contrast CT beyond the coronary calcium scan

    PubMed Central

    Madaj, Paul; Budoff, Matthew J.

    2014-01-01

    Coronary artery calcification (CAC) is a well-known marker for coronary artery disease and has important prognostic implications. CAC is able to provide clinicians with a reliable source of information related to cardiovascular atherosclerosis, which carries incremental information beyond Framingham risk. However, non-contrast scans of the heart provide additional information beyond the Agatston score. These studies are also able to measure various sources of fat, including intrathoracic (eg, pericardial or epicardial) and hepatic, both of which are thought to be metabolically active and linked to increased incidence of subclinical atherosclerosis as well as increased prevalence of type 2 diabetes. Testing for CAC is also useful in identifying extracoronary sources of calcification. Specifically, aortic valve calcification, mitral annular calcification, and thoracic aortic calcium (TAC) provide additional risk stratification information for cardiovascular events. Finally, scanning for CAC is able to evaluate myocardial scaring due to myocardial infarcts, which may also add incremental prognostic information. To ensure the benefits outweigh the risks of a scanning for CAC for an appropriately selected asymptomatic patient, the full utility of the scan should be realized. This review describes the current state of the art interpretation of non-contrast cardiac CT, which clinically should go well beyond coronary artery Agatston scoring alone. PMID:22981856

  19. CK-MB isoforms for early risk stratification of emergency department patients.

    PubMed

    Green, G B; Dehlinger, E; McGrievey, T S; Li, D J; Jones, K A; Kelen, G D; Chan, D W

    2000-10-01

    The potential clinical utility of single sample CK-MB isoforms measurement for early risk stratification of Emergency Department (ED) patients with possible myocardial ischemia was evaluated among 405 patients presenting to two urban EDs. Clinical and serologic data were prospectively collected and the occurrence of adverse events (AEs) and myocardial infarction (MI) during the 14-day outcome period was recorded and utilized to calculate and compare relative risks (RR) and predictive values of isoforms and CK-MB alone. Among the 405 patients, 67 accrued 105 AEs. Both isoforms and CK-MB alone were predictive of AEs with RR of 3.32 (2.09, 5.27) and 6.28 (4.64, 8.52), respectively. Isoforms had higher sensitivity for AEs compared to CK-MB (65.7% [54.3, 77.0] vs. 14.9% [6.4, 23.5]; p<0. 01) but lower specificity (69.2% [64.3, 74.2] vs. 99.7% [99.1,100. 0]; p<0.01). Isoforms' superior sensitivity allowed identification of many high risk patients missed by CK-MB alone. Further, for the prediction of MI, isoforms had superior diagnostic sensitivity and equivalent specificity. This investigation supports the emergency department use of early, single sample CK-MB isoform testing. PMID:10958863

  20. Noninvasive risk stratification after myocardial infarction: rationale, current evidence and the need for definitive trials.

    PubMed

    Exner, Derek

    2009-06-01

    Despite advances in therapies for myocardial infarction (MI), death attributed to a cardiac arrest from ventricular tachycardia (VT) or ventricular fibrillation (VF) remains an important problem. The implantable cardioverter defibrillator (ICD) is effective in preventing death from VT/VF, but reliably identifying which post-MI patients would benefit from an ICD remains a major challenge. Beyond the initial post-MI period, the presence of significant left ventricular (LV) dysfunction, alone or in combination with the induction of sustained VT/VF during invasive testing, is the only proven means of selecting patients for a prophylactic ICD. However, these approaches identify only a fraction of those at risk. Furthermore, most patients with significant LV dysfunction after MI have a low, near-term risk of VT/VF. Noninvasive risk stratification tools have been developed to better identify patients likely to benefit from an ICD. To date, none of these tools has been proven useful in this regard. The factors leading to a cardiac arrest are complex, and a single test is unlikely to reliably predict risk. Noninvasive assessment of cardiac structure, conduction and repolarization along with autonomic modulation appear to be useful in predicting the risk of a cardiac arrest after MI, particularly when assessed in combination. However, randomized trials assessing the efficacy of ICD therapy in patients identified as being at risk are required. Until such data are available, significant LV dysfunction alone and in combination with the induction of VT/VF during invasive testing in the nonacute post-MI period remain the only proven methods to guide prophylactic ICD therapy. PMID:19521570

  1. ECG Morphological Variability in Beat Space for Risk Stratification After Acute Coronary Syndrome

    PubMed Central

    Liu, Yun; Syed, Zeeshan; Scirica, Benjamin M.; Morrow, David A.; Guttag, John V.; Stultz, Collin M.

    2014-01-01

    Background Identification of patients who are at high risk of adverse cardiovascular events after an acute coronary syndrome (ACS) remains a major challenge in clinical cardiology. We hypothesized that quantifying variability in electrocardiogram (ECG) morphology may improve risk stratification post‐ACS. Methods and Results We developed a new metric to quantify beat‐to‐beat morphologic changes in the ECG: morphologic variability in beat space (MVB), and compared our metric to published ECG metrics (heart rate variability [HRV], deceleration capacity [DC], T‐wave alternans, heart rate turbulence, and severe autonomic failure). We tested the ability of these metrics to identify patients at high risk of cardiovascular death (CVD) using 1082 patients (1‐year CVD rate, 4.5%) from the MERLIN‐TIMI 36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non‐ST‐Elevation Acute Coronary Syndrome—Thrombolysis in Myocardial Infarction 36) clinical trial. DC, HRV/low frequency–high frequency, and MVB were all associated with CVD (hazard ratios [HRs] from 2.1 to 2.3 [P<0.05 for all] after adjusting for the TIMI risk score [TRS], left ventricular ejection fraction [LVEF], and B‐type natriuretic peptide [BNP]). In a cohort with low‐to‐moderate TRS (N=864; 1‐year CVD rate, 2.7%), only MVB was significantly associated with CVD (HR, 3.0; P=0.01, after adjusting for LVEF and BNP). Conclusions ECG morphological variability in beat space contains prognostic information complementary to the clinical variables, LVEF and BNP, in patients with low‐to‐moderate TRS. ECG metrics could help to risk stratify patients who might not otherwise be considered at high risk of CVD post‐ACS. PMID:24963105

  2. Noninvasive risk stratification after myocardial infarction: Rationale, current evidence and the need for definitive trials

    PubMed Central

    Exner, Derek V

    2009-01-01

    Despite advances in therapies for myocardial infarction (MI), death attributed to a cardiac arrest from ventricular tachycardia (VT) or ventricular fibrillation (VF) remains an important problem. The implantable cardioverter defibrillator (ICD) is effective in preventing death from VT/VF, but reliably identifying which post-MI patients would benefit from an ICD remains a major challenge. Beyond the initial post-MI period, the presence of significant left ventricular (LV) dysfunction, alone or in combination with the induction of sustained VT/VF during invasive testing, is the only proven means of selecting patients for a prophylactic ICD. However, these approaches identify only a fraction of those at risk. Furthermore, most patients with significant LV dysfunction after MI have a low, near-term risk of VT/VF. Noninvasive risk stratification tools have been developed to better identify patients likely to benefit from an ICD. To date, none of these tools has been proven useful in this regard. The factors leading to a cardiac arrest are complex, and a single test is unlikely to reliably predict risk. Noninvasive assessment of cardiac structure, conduction and repolarization along with autonomic modulation appear to be useful in predicting the risk of a cardiac arrest after MI, particularly when assessed in combination. However, randomized trials assessing the efficacy of ICD therapy in patients identified as being at risk are required. Until such data are available, significant LV dysfunction alone and in combination with the induction of VT/VF during invasive testing in the nonacute post-MI period remain the only proven methods to guide prophylactic ICD therapy. PMID:19521570

  3. Objective estimates improve risk stratification for primary graft dysfunction after lung transplantation

    PubMed Central

    Shah, Rupal J.; Diamond, Joshua M.; Cantu, Edward; Flesch, Judd; Lee, James C.; Lederer, David J.; Lama, Vibha N.; Orens, Jonathon; Weinacker, Ann; Wilkes, David S.; Roe, David; Bhorade, Sangeeta; Wille, Keith M.; Ware, Lorraine B.; Palmer, Scott M.; Crespo, Maria; Demissie, Ejigayehu; Sonnet, Joshua; Shah, Ashish; Kawut, Steven M.; Bellamy, Scarlett L.; Localio, A. Russell; Christie, Jason D.

    2016-01-01

    Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002–2010; with separate validation in 382 subjects accrued from 2011–2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 hours, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed 3 prediction models, where low-risk recipients had a normal BMI (18.5–25 kg/m2), COPD/CF, and absent or mild PH (mPAP< 40mmHg). All others were considered higher-risk. Low-risk recipients had a predicted PGD risk of 4–7%, and high-risk a predicted PGD risk of 15–18%. Adding a donor-smoking lung to a higher-risk recipient significantly increased PGD risk, although risk did not change in low-risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5–25%. We conclude that valid estimates of PGD risk can be produced using readily-available clinical variables. PMID:25877792

  4. Cardiac Magnetic Resonance Scar Imaging for Sudden Cardiac Death Risk Stratification in Patients with Non-Ischemic Cardiomyopathy

    PubMed Central

    Kim, Eun Kyoung; Chattranukulchai, Pairoj

    2015-01-01

    In patients with non-ischemic cardiomyopathy (NICM), risk stratification for sudden cardiac death (SCD) and selection of patients who would benefit from prophylactic implantable cardioverter-defibrillators remains challenging. We aim to discuss the evidence of cardiac magnetic resonance (CMR)-derived myocardial scar for the prediction of adverse cardiovascular outcomes in NICM. From the 15 studies analyzed, with a total of 2747 patients, the average prevalence of myocardial scar was 41%. In patients with myocardial scar, the risk for adverse cardiac events was more than 3-fold higher, and risk for arrhythmic events 5-fold higher, as compared to patients without scar. Based on the available observational, single center studies, CMR scar assessment may be a promising new tool for SCD risk stratification, which merits further investigation. PMID:26175568

  5. Arrhythmic risk stratification after myocardial infarction using ambulatory electrocardiography signal averaging.

    PubMed

    Roche, Frédéric; DaCosta, Antoine; Karnib, Ibrahim; Triomphe, Géraldine; Roche, Christian; Isaaz, Karl; Geyssant, André; Barthélémy, Jean-Claude

    2002-05-01

    Ambulatory ECG had been proposed to examine the amplified high resolution signal-averaged electrocardiogram (SAECG). Clinical investigations are required to confirm the predictive value of such a high resolution technique in arrhythmic risk stratification. The prognostic value of ambulatory Holter SAECG was evaluated in 108 postinfarction patients for the purpose of predicting the occurrence of serious arrhythmic (SARR) events (sudden cardiac death [SCD], VT, or VF) in comparison with classical real-time SAECG. During the 42+/-8 months of follow-up, the sudden cardiac death mortality was 4.6% (five deaths), six (5.6%) patients had VT, and one (0.9%) VF. QRSd was found to be the most predictive parameter using ROC curves analysis for SAAR + outcome (W = 0.833 and W = 0.803 for 25-250 Hz and 40-250 Hz filters, respectively) followed by RMS (W = 0.766 and W = 0.721) and LAS (W = 0.759, W = 0.709) (all P < 0.01). Abnormal Holter SAECG for 25 and 40-Hz LP filter were significant predictors of SARR+ by log-rank test (P < 0.01, P < 0.05, respectively). This study confirms that valuable prognostic information can be obtained from the ambulatory high resolution ECG technique and that Holter SAECG may predict arrhythmic risk in a postinfarction population. PMID:12049370

  6. Post-Myocardial Infarction Arrhythmia Risk Stratification Using Microvolt T-Wave Alternans

    PubMed Central

    Donoiu, I.; Mirea, Oana Cristina; Giuca, Alina; Militaru, C.; Ionescu, D.D.

    2012-01-01

    Since its initial description, a number of studies have described the use of microvolt T-wave alternans (MTWA) as a predictor of the primary or secondary occurrence of ventricular arrhythmic events. These studies, however, have been limited by small sample sizes and disparate patient populations. Studies of MTWA in post-myocardial infarction (MI) patients are few in number, but hold predictive value for risk of ventricular arrhythmias. We performed a study of MTWA in post-myocardial infarction patients to clarify the predictive accuracy and usefulness of MTWA compared to other invasive and non-invasive techniques. We enrolled 120 patients (74 men, 46 women, mean age 62.3 ± 15.2 years in men, and 64.2 ± 13.8 years in women) with a history of myocardial infarction but no prior sustained ventricular arrhythmias. Patients were assessed by echocardiography, Holter, signal averaged ECG, MTWA, and electrophysiology study. Mean follow-up was 14 months. The MTWA test had a good negative predictive value for arrhythmic events in post-MI patients and can be used for risk stratification. We consider that in patients with positive MTWA further invasive evaluation, respectively electrophysiology study, is necessary. PMID:24778843

  7. The RAG Model: A New Paradigm for Genetic Risk Stratification in Multiple Myeloma

    PubMed Central

    Prideaux, Steven M.; Conway O'Brien, Emma; Chevassut, Timothy J.

    2014-01-01

    Molecular studies have shown that multiple myeloma is a highly genetically heterogonous disease which may manifest itself as any number of diverse subtypes each with variable clinicopathological features and outcomes. Given this genetic heterogeneity, a universal approach to treatment of myeloma is unlikely to be successful for all patients and instead we should strive for the goal of personalised therapy using rationally informed targeted strategies. Current DNA sequencing technologies allow for whole genome and exome analysis of patient myeloma samples that yield vast amounts of genetic data and provide a mutational overview of the disease. However, the clinical utility of this information currently lags far behind the sequencing technology which is increasingly being incorporated into clinical practice. This paper attempts to address this shortcoming by proposing a novel genetically based “traffic-light” risk stratification system for myeloma, termed the RAG (Red, Amber, Green) model, which represents a simplified concept of how complex genetic data may be compressed into an aggregate risk score. The model aims to incorporate all known clinically important trisomies, translocations, and mutations in myeloma and utilise these to produce a score between 1.0 and 3.0 that can be incorporated into diagnostic, prognostic, and treatment algorithms for the patient. PMID:25295194

  8. The RAG Model: A New Paradigm for Genetic Risk Stratification in Multiple Myeloma.

    PubMed

    Prideaux, Steven M; Conway O'Brien, Emma; Chevassut, Timothy J

    2014-01-01

    Molecular studies have shown that multiple myeloma is a highly genetically heterogonous disease which may manifest itself as any number of diverse subtypes each with variable clinicopathological features and outcomes. Given this genetic heterogeneity, a universal approach to treatment of myeloma is unlikely to be successful for all patients and instead we should strive for the goal of personalised therapy using rationally informed targeted strategies. Current DNA sequencing technologies allow for whole genome and exome analysis of patient myeloma samples that yield vast amounts of genetic data and provide a mutational overview of the disease. However, the clinical utility of this information currently lags far behind the sequencing technology which is increasingly being incorporated into clinical practice. This paper attempts to address this shortcoming by proposing a novel genetically based "traffic-light" risk stratification system for myeloma, termed the RAG (Red, Amber, Green) model, which represents a simplified concept of how complex genetic data may be compressed into an aggregate risk score. The model aims to incorporate all known clinically important trisomies, translocations, and mutations in myeloma and utilise these to produce a score between 1.0 and 3.0 that can be incorporated into diagnostic, prognostic, and treatment algorithms for the patient. PMID:25295194

  9. A new method for IVUS-based coronary artery disease risk stratification: A link between coronary & carotid ultrasound plaque burdens.

    PubMed

    Araki, Tadashi; Ikeda, Nobutaka; Shukla, Devarshi; Londhe, Narendra D; Shrivastava, Vimal K; Banchhor, Sumit K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Suri, Jasjit S

    2016-02-01

    Interventional cardiologists have a deep interest in risk stratification prior to stenting and percutaneous coronary intervention (PCI) procedures. Intravascular ultrasound (IVUS) is most commonly adapted for screening, but current tools lack the ability for risk stratification based on grayscale plaque morphology. Our hypothesis is based on the genetic makeup of the atherosclerosis disease, that there is evidence of a link between coronary atherosclerosis disease and carotid plaque built up. This novel idea is explored in this study for coronary risk assessment and its classification of patients between high risk and low risk. This paper presents a strategy for coronary risk assessment by combining the IVUS grayscale plaque morphology and carotid B-mode ultrasound carotid intima-media thickness (cIMT) - a marker of subclinical atherosclerosis. Support vector machine (SVM) learning paradigm is adapted for risk stratification, where both the learning and testing phases use tissue characteristics derived from six feature combinational spaces, which are then used by the SVM classifier with five different kernels sets. These six feature combinational spaces are designed using 56 novel feature sets. K-fold cross validation protocol with 10 trials per fold is used for optimization of best SVM-kernel and best feature combination set. IRB approved coronary IVUS and carotid B-mode ultrasound were jointly collected on 15 patients (2 days apart) via: (a) 40MHz catheter utilizing iMap (Boston Scientific, Marlborough, MA, USA) with 2865 frames per patient (42,975 frames) and (b) linear probe B-mode carotid ultrasound (Toshiba scanner, Japan). Using the above protocol, the system shows the classification accuracy of 94.95% and AUC of 0.95 using optimized feature combination. This is the first system of its kind for risk stratification as a screening tool to prevent excessive cost burden and better patients' cardiovascular disease management, while validating our two hypotheses

  10. Risk stratification of patients with hypertension using exercise thallium-201 scintigraphy

    SciTech Connect

    Iskandrian, A.S.; Hakki, A.H.; Kane, S.

    1985-05-01

    Hypertension (HT) is an important risk factor in coronary heart disease (CHD) and cardiac morbidity and mortality. This study examined the value of clinical, ECG, exercise (EX) and thallium-201 imaging descriptors that identify patients (pts) with HT at high risk. The 337 pts in the study underwent EX thallium-201 testing for evaluation of chest pain due to suspected or proven CHD. The mean age was 55 years, of whom 79% were still on active anti-HT therapy at the time of the study. The EX thallium scintigrams were evaluated qualitatively and quantitively using circumferential profile analysis. The scans were abnormal in 162 pts (48%) and reversible perfusion defects were present in 106 of the 162 pts (65%). At a folllowup fo up to 74 months, (15 +- 9 mean +- SD), 11 pts had hard cardiac events: 2 died of cardiac causes and 9 had non-fatal acute myocardial infractions. There were no significant differences between those with and without events in age, EX heart rate and double product, EX duration, blood pressure and EX ECG changes. Univariate and multivariate survival analysis (Cox regression model) of important clinical, ECG, EX and thallium variables, identified the presence of abnormal EX images as the only predictor of outcome. (X/sup 2/ = 5.4, p< 0.02). No other variable provided additional prognostic information. Actuarial life table analysis showed that pts with abnormal images had significantly more events than those with normal images (p = 0.008, Mantel-Cox). Thus, EX thallium imaging is useful in risk stratification in pts with HT. The presence of abnormal images identify a subgroup at high risk for future events.

  11. Emergency department management of syncope: need for standardization and improved risk stratification.

    PubMed

    Thiruganasambandamoorthy, Venkatesh; Taljaard, Monica; Stiell, Ian G; Sivilotti, Marco L A; Murray, Heather; Vaidyanathan, Aparna; Rowe, Brian H; Calder, Lisa A; Lang, Eddy; McRae, Andrew; Sheldon, Robert; Wells, George A

    2015-08-01

    Variations in emergency department (ED) syncope management have not been well studied. The goals of this study were to assess variations in management, and emergency physicians' risk perception and disposition decision making. We conducted a prospective study of adults with syncope in six EDs in four cities over 32 months. We collected patient characteristics, ED management, disposition, physicians' prediction probabilities at index presentation and followed patients for 30 days for serious outcomes: death, myocardial infarction (MI), arrhythmia, structural heart disease, pulmonary embolism, significant hemorrhage, or procedural interventions. We used descriptive statistics, ROC curves, and regression analyses. We enrolled 3662 patients: mean age 54.3 years, and 12.9 % were hospitalized. Follow-up data were available for 3365 patients (91.9 %) and 345 patients (10.3 %) suffered serious outcomes: 120 (3.6 %) after ED disposition including 48 patients outside the hospital. After accounting for differences in patient case mix, the rates of ED investigations and disposition were significantly different (p < 0.0001) across the four study cities; as were the rates of 30-day serious outcomes (p < 0.0001) and serious outcomes after ED disposition (p = 0.0227). There was poor agreement between physician risk perception and both observed event rates and referral patterns (p < 0.0001). Only 76.7 % (95 % CI 68.1-83.6) of patients with serious outcomes were appropriately referred. There are large and unexplained differences in ED syncope management. Moreover, there is poor agreement between physician risk perception, disposition decision making, and serious outcomes after ED disposition. A valid risk-stratification tool might help standardize ED management and improve disposition decision making. PMID:25918108

  12. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder

    PubMed Central

    Perlis, Roy

    2013-01-01

    Background Early identification of depressed individuals at high risk for treatment-resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Methods Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by, or readily amenable to, self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacologic treatment trial from those not reaching remission despite two trials. Results A logistic regression model achieved an area under the receiver operating characteristic curve (AUC) exceeding 0.71 in training, testing and validation cohorts, and maintained good calibration across cohorts. Performance of three alternative models using machine learning approaches–a naïve Bayes classifier and a support vector machine, and a random forest model – was less consistent. Similar performance was observed between more and less severe depression, males and females, and primary versus specialty care sites. A web-based calculator was developed which implements this tool and provides graphical estimates of risk. Conclusion Risk for treatment-resistance among outpatients with major depressive disorder can be estimated using a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Registration Sequential Treatment Alternatives to Relieve Depression (STAR*D); NCT00021528; www.star-d.org PMID:23380715

  13. Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study.

    PubMed

    de Rooij, Jasmijn D E; Masetti, Riccardo; van den Heuvel-Eibrink, Marry M; Cayuela, Jean-Michel; Trka, Jan; Reinhardt, Dirk; Rasche, Mareike; Sonneveld, Edwin; Alonzo, Todd A; Fornerod, Maarten; Zimmermann, Martin; Pigazzi, Martina; Pieters, Rob; Meshinchi, Soheil; Zwaan, C Michel; Locatelli, Franco

    2016-06-30

    Genetic abnormalities and early treatment response are the main prognostic factors in acute myeloid leukemia (AML). Acute megakaryoblastic leukemia (AMKL) is a rare subtype of AML. Deep sequencing has identified CBFA2T3/GLIS2 and NUP98/KDM5A as recurrent aberrations, occurring in similar frequencies as RBM15/MKL1 and KMT2A-rearrangements. We studied whether these cytogenetic aberrations can be used for risk group stratification. To assess frequencies and outcome parameters of recurrent cytogenetic aberrations in AMKL, samples and clinical data of patients treated by the Associazione Italiana Ematologia Oncologia Pediatrica, Berlin-Frankfurt-Munster Study Group, Children's Oncology Group, Dutch Childhood Oncology Group, and the Saint Louis Hôpital were collected, enabling us to screen 153 newly diagnosed pediatric AMKL cases for the aforementioned aberrations and to study their clinical characteristics and outcome. CBFA2T3/GLIS2 was identified in 16% of the cases; RBM15/MKL1, in 12%; NUP98/KDM5A and KMT2A rearrangements, in 9% each; and monosomy 7, in 6%. These aberrations were mutually exclusive. RBM15/MKL1-rearranged patients were significantly younger. No significant differences in sex and white blood cell count were found. NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearranged lesions and monosomy 7 (NCK-7) independently predicted a poor outcome, compared with RBM15/MKL1-rearranged patients and those with AMKL not carrying these molecular lesions. NCK-7-patients (n = 61) showed a 4-year probability of overall survival of 35 ± 6% vs 70 ± 5% in the RBM15/MKL1-other groups (n = 92, P < .0001) and 4-year probability of event-free survival of 33 ± 6% vs 62 ± 5% (P = .0013), the 4-year cumulative incidence of relapse being 42 ± 7% and 19 ± 4% (P = .003), respectively. We conclude that these genetic aberrations may be used for risk group stratification of pediatric AMKL and for treatment tailoring. PMID:27114462

  14. Iodine-123-metaiodobenzylguanidine scintigraphy in risk stratification of sudden death in heart failure.

    PubMed

    Martins da Silva, Marta Inês; Vidigal Ferreira, Maria João; Morão Moreira, Ana Paula

    2013-06-01

    Metaiodobenzylguanidine (MIBG) is a false neurotransmitter noradrenaline analogue that is taken up by the 'uptake 1' transporter mechanism in the cell membrane of presynaptic adrenergic neurons and accumulates in catecholamine storage vesicles. Since it is practically unmetabolized, it can be labeled with a radioisotope (iodine-123) in scintigraphic exams to noninvasively assess the functional status of the sympathetic innervation of organs with a significant adrenergic component, including the heart. Studies of its application in nuclear cardiology appear to confirm its value in the assessment of conditions such as coronary artery disease, heart failure, arrhythmias and sudden death. Heart failure is a global problem, with an estimated prevalence of 2% in developed countries. Sudden cardiac death is the main cause of its high mortality. The autonomic nervous system dysfunction, including sympathetic hyperactivity, that accompanies chronic heart failure is associated with progressive myocardial remodeling, declining left ventricular function and worsening symptoms, and contributes to the development of ventricular arrhythmias and sudden death. Since 123I-MIBG cardiac scintigraphy can detect changes in the cardiac adrenergic system, there is considerable interest in its role in obtaining diagnostic and prognostic information in patients with heart failure. In this article we present a literature review on the use of 123I-MIBG scintigraphy for risk stratification of sudden death in patients with heart failure. PMID:23731734

  15. Mortality risk stratification in elderly trauma patients based on initial arterial lactate and base deficit levels.

    PubMed

    Neville, Angela L; Nemtsev, Denis; Manasrah, Raed; Bricker, Scott D; Putnam, Brant A

    2011-10-01

    Elderly trauma patients have worse outcomes than their younger counterparts. Early risk stratification remains difficult, particularly because traditional vital signs are less reliable. We hypothesized that arrival lactate and base deficit (BD) could be used to predict mortality in elderly trauma patients with a normal admission blood pressure. We retrospectively evaluated the prospectively collected trauma registry at our urban Level I trauma center between 2003 and 2009. Patients sustaining blunt trauma, age 55 years or older, with a systolic blood pressure 90 mmHg or higher, and who had arterial lactate and/or BD measured within 4 hours of arrival comprised the study group. Primary outcomes were in-hospital and 24-hour mortality. There were 364 patients with a lactate and 324 with a BD drawn. Patients with a lactate 2.5 mmol or greater were 3.7 times more likely to die than those with a lactate less than 2.5 mmol (95% CI, 1.6 to 8.2; P = 0.0018). The OR for mortality was 5.2 (95% CI, 2.5 to 11.2; P < 0.0001) in patients with a BD -4 or less. Elevated lactate and BD were even stronger predictors of early mortality (within first 24 hours). After increasing the hypotension threshold to a systolic blood pressure 110 mmHg or greater, lactate and BD remained highly predictive of in-hospital and 24-hour mortality. PMID:22127083

  16. Electrocardiographic methods for diagnosis and risk stratification in the Brugada syndrome.

    PubMed

    Naseef, Abdulrahman; Behr, Elijah R; Batchvarov, Velislav N

    2015-04-01

    The Brugada syndrome (BrS) is a malignant, genetically-determined, arrhythmic syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals with structurally normal hearts. The diagnosis of the BrS is mainly based on the presence of a spontaneous or Na + channel blocker induced characteristic, electrocardiographic (ECG) pattern (type 1 or coved Brugada ECG pattern) typically seen in leads V1 and V2 recorded from the 4th to 2nd intercostal (i.c.) spaces. This pattern needs to be distinguished from similar ECG changes due to other causes (Brugada ECG phenocopies). This review focuses mainly on the ECG-based methods for diagnosis and arrhythmia risk assessment in the BrS. Presently, the main unresolved clinical problem is the identification of those patients at high risk of SCD who need implantable cardioverter-defibrillator (ICD), which is the only therapy with proven efficacy. Current guidelines recommend ICD implantation only in patients with spontaneous type 1 ECG pattern, and either history of aborted cardiac arrest or documented sustained VT (class I), or syncope of arrhythmic origin (class IIa) because they are at high risk of recurrent arrhythmic events (up to 10% or more annually for those with aborted cardiac arrest). The majority of BrS patients are asymptomatic when diagnosed and considered to have low risk (around 0.5% annually) and therefore not indicated for ICD. The majority of SCD victims in the BrS, however, had no symptoms prior to the fatal event and therefore were not protected with an ICD. While some ECG markers such as QRS fragmentation, infero-lateral early repolarisation, and abnormal late potentials on signal-averaged ECG are known to be linked to increased arrhythmic risk, they are not sufficiently sensitive or specific. Potential novel ECG-based strategies for risk stratification are discussed based on computerised methods for depolarisation and repolarisation analysis, a composite approach targeting several major

  17. Plasma copeptin for short term risk stratification in acute pulmonary embolism.

    PubMed

    Wyzgał, Anna; Koć, Marcin; Pacho, Szymon; Bielecki, Maksymilian; Wawrzyniak, Radosław; Kostrubiec, Maciej; Ciurzyński, Michał; Kurnicka, Katarzyna; Goliszek, Sylwia; Paczyńska, Marzena; Palczewski, Piotr; Pruszczyk, Piotr

    2016-05-01

    Copeptin (COP) was reported to have prognostic value in various cardiovascular diseases. We hypothesized that COP levels reflect the severity of acute pulmonary embolism (PE) and may be useful in prognostic assessment. Plasma COP concentrations were measured on the Kryptor Compact Plus platform (BRAHMS, Hennigsdorf, Germany). The study included 107 consecutive patients with diagnosed acute PE (47 males, 60 females), with median age of 65 years (range 20-88). High risk PE was diagnosed in 3 patients (2.8 %), intermediate risk in 69 (64.5 %), and low risk PE in 35 (32.7 %) patients. Control group included 64 subjects (25 males, 39 females; median age 52.5 year, range 17-87). Four patients (3.7 %) died during 30-day observation. Complicated clinical course (CCC) was experienced by 10 (9.3 %) patients. COP level was higher in PE patients than in controls [11.55 pmol/L (5.16-87.97), and 19.00 pmol/L (5.51-351.90), respectively, p < 0.0001], and reflected PE severity. COP plasma concentration in low risk PE was 14.67 nmol/L (5.51-59.61) and in intermediate/high risk PE 19.84 mol/L (5.64-351.90) p < 0.05. Median COP levels in nonsurvivors was higher than in survivors, 84.6 (28.48-351.9) pmol/L and 18.68 (5.512-210.1) pmol/L, respectively, p = 0.009. Subjects with CCC presented higher COP levels than patients with benign clinical course 53.1 (17.95-351.9) pmol/L and 18.16 (5.51-210.1) pmol/L, respectively, p = 0.001. Log-transformed plasma COP was the significant predictor of CCC, OR 16.5 95 % CI 23.2-111.9, p < 0.001. AUC-for prediction of CCC using plasma COP was 0.811 (95 % CI 0.676-0.927). The COP cut off value of 17.95 nmol/l had sensitivity of 100 %, specificity 49.5 %, positive predictive value of 16.9 % and negative predictive value of 100 %. We conclude that plasma COP levels can be regarded for promising marker of severity of acute PE and show potential in risk stratification of these patients. PMID:26438275

  18. Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

    PubMed Central

    Bleeker, Jonathan S.; Hogan, William J.

    2011-01-01

    Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

  19. Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification

    PubMed Central

    Kansal, Rina

    2016-01-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in 2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML. PMID:27144061

  20. Prognostic value of angiopoietin-2 for death risk stratification in patients with metastatic colorectal carcinoma

    PubMed Central

    Jary, Marine; Vernerey, Dewi; Lecomte, Thierry; Dobi, Erion; Ghiringhelli, François; Monnien, Franck; Godet, Yann; Kim, Stefano; Bouché, Olivier; Fratte, Serge; Gonçalves, Anthony; Leger, Julie; Queiroz, Lise; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe

    2015-01-01

    Background Baseline prognostic biomarkers stratifying treatment strategies in first-line metastatic colorectal cancer (mCRC) are lacking. Angiopoietin-2 (Ang-2) is proposed as a potential biomarker in several cancers. We therefore decided to establish the additional prognostic value of Ang-2 for overall survival (OS) in first-line mCRC patients. Methods We enrolled 177 patients treated with a bevacizumab containing chemotherapy in two prospective phase II clinical trials. Patient plasma samples were collected at baseline. Enzyme-linked immunosorbent assays were used to measure Ang-2. Results The multivariable Cox model identified increased LDH (HR=1.60, 95%CI: 1.04–2.45, p=0.03) and Ang-2 log-transformation level (HR=1.59, 95%CI: 1.14–2.21, p=0.0065) as two significant independent OS prognostic factors. It exhibited good calibration (p=0.8) and discrimination (C-index: 0.64; 95%CI: 0.58–0.68). Ang-2 parameter inclusion in the GERCOR reference model significantly and strongly improved its discriminative ability since the C-statistic increased significantly from 0.61 to 0.63 (bootstrap mean difference=0.07, 95%CI: 0.069–0.077). Interestingly, the addition of Ang-2 binary information with a 5 ng/mL cut-off value to the GERCOR model allowed the reclassification of intermediate-risk profile patients (41%) into two subsets of low and high-risks. Conclusions Our study provides robust evidence in favour of baseline Ang-2 prognostic value for OS adding to the conventional factors. Its assessment appears to be useful for the improvement in risk stratification for patients with intermediate-risk profile. Impact Ang-2 ability to predict OS at diagnosis could be of interest in the selection of patients eligible to intermittent or sequential therapeutic strategies dedicated to the optimization of patient’s quality of life and chemotherapy cost-effectiveness. PMID:25583947

  1. Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease

    PubMed Central

    Sengupta, Dibyendu; Kahn, Andrew M.; Kung, Ethan; Moghadam, Mahdi Esmaily; Shirinsky, Olga; Lyskina, Galina A.; Burns, Jane C.; Marsden, Alison L.

    2016-01-01

    Kawasaki disease (KD) is the leading cause of acquired heart disease in children and can result in life-threatening coronary artery aneurysms in up to 25 % of patients. These aneurysms put patients at risk of thrombus formation, myocardial infarction, and sudden death. Clinicians must therefore decide which patients should be treated with anticoagulant medication, and/or surgical or percutaneous intervention. Current recommendations regarding initiation of anticoagulant therapy are based on anatomy alone with historical data suggesting that patients with aneurysms ≥8 mm are at greatest risk of thrombosis. Given the multitude of variables that influence thrombus formation, we postulated that hemodynamic data derived from patient-specific simulations would more accurately predict risk of thrombosis than maximum diameter alone. Patient-specific blood flow simulations were performed on five KD patients with aneurysms and one KD patient with normal coronary arteries. Key hemodynamic and geometric parameters, including wall shear stress, particle residence time, and shape indices, were extracted from the models and simulations and compared with clinical outcomes. Preliminary fluid structure interaction simulations with radial expansion were performed, revealing modest differences in wall shear stress compared to the rigid wall case. Simulations provide compelling evidence that hemodynamic parameters may be a more accurate predictor of thrombotic risk than aneurysm diameter alone and motivate the need for follow-up studies with a larger cohort. These results suggest that a clinical index incorporating hemodynamic information be used in the future to select patients for anticoagulant therapy. PMID:24722951

  2. Prognostic value of health-related quality of life for death risk stratification in patients with unresectable glioblastoma.

    PubMed

    Paquette, Brice; Vernerey, Dewi; Chauffert, Bruno; Dabakuyo, Sandrine; Feuvret, Loic; Taillandier, Luc; Frappaz, Didier; Taillia, Hervé; Schott, Roland; Ducray, François; Fabbro, Michel; Tennevet, Isabelle; Ghiringhelli, François; Guillamo, Jean-Sébastien; Durando, Xavier; Castera, Daniel; Frenay, Marc; Campello, Chantal; Dalban, Cécile; Skrzypski, Jérome; Chinot, Olivier; Anota, Amélie; Bonnetain, Franck

    2016-08-01

    Glioblastoma is the most common malignant brain tumor in adults. Baseline health-related quality of life (HRQoL) is a major subject of concern for these patients. We aimed to assess the independent prognostic value of HRQoL in unresectable glioblastoma (UGB) patients for death risk stratification. One hundred and thirty-four patients with UGB were enrolled from the TEMAVIR trial. HRQoL was evaluated at baseline using the EORTC QLQ-C30 and BN20 brain cancer module. Clinical and HRQoL parameters were evaluated in univariable and multivariable Cox analysis as prognostic factors for overall survival (OS). Performance assessment and internal validation of the final model were evaluated with Harrel's C-index, calibration plot, and bootstrap sample procedure. Two OS independent predictors were identified: future uncertainty and sensitivity deficit. The final model exhibited good calibration and acceptable discrimination (C statistic = 0.63). The internal validity of the model was verified with robust uncertainties around the hazard ratio. The prognostic score identified three groups of patients with distinctly different risk profiles with median OS estimated at 16.2, 9.2, and 4.5 months. We demonstrated the additional prognostic value of HRQoL in UGB for death risk stratification and provided a score that may help to guide clinical management and stratification in future clinical trials. PMID:27252150

  3. Accurately Determining the Risks of Rising Sea Level

    NASA Astrophysics Data System (ADS)

    Marbaix, Philippe; Nicholls, Robert J.

    2007-10-01

    With the highest density of people and the greatest concentration of economic activity located in the coastal regions, sea level rise is an important concern as the climate continues to warm. Subsequent flooding may potentially disrupt industries, populations, and livelihoods, particularly in the long term if the climate is not quickly stabilized [McGranahan et al., 2007; Tol et al., 2006]. To help policy makers understand these risks, a more accurate description of hazards posed by rising sea levels is needed at the global scale, even though the impacts in specific regions are better known.

  4. Ventricular arrhythmias in competitive athletes: risk stratification with T-wave alternans

    PubMed Central

    INAMA, GIUSEPPE; PEDRINAZZI, CLAUDIO; DURIN, ORNELLA; NANETTI, MASSIMILIANO; DONATO, GIORGIO; PIZZI, RITA

    2007-01-01

    Introduction: Aim of our study is to evaluate the role of TWA to stratify the risk of sudden cardiac death in athletes (Ath) with complex ventricular arrhythmias (VA), and to document a possible correlation between TWA and electrophysiological testing (EES) results. Methods: We studied 43 Ath with VA (31 M, mean age 34 ± 12 years). In all cases a cardiological evaluation was performed, including TWA and EES. The patients were evaluated during a follow-up of 25 ± 22 months. The end-point was the occurrence of sudden death or malignant ventricular tachyarrhythmias (VT). Results: TWA was negative in 28 Ath (65%), positive in 8 (19%) and indeterminate in 7 (16%). All subjects with negative TWA did not show induction of VT at EES, with significant correlation between negative TWA and negative EES (p<0.001). All Ath with positive TWA also had VT induced by a EES, but without significant correlation between positive TWA and positive EES. In 2 Ath with undetermined TWA (29%) VT were induced at EES. Our data did not show significant correlation between indeterminate TWA and positive or negative EES. However, logistic regression analysis showed significant correlation between abnormal TWA test (positive or indeterminate) and inducibility of VT at EES (p<0.001). During follow-up we observed a significant difference in end-point occurrence between Ath with negative or positive TWA and between Ath with negative or positive EES. Conclusion: TWA confirm its role as a simple and non-invasive test, and it seems useful for prognostic stratification of Ath with VA. PMID:21977276

  5. Dynamic risk stratification for medullary thyroid cancer according to the response to initial therapy.

    PubMed

    Kwon, Hyemi; Kim, Won Gu; Jeon, Min Ji; Song, Dong Eun; Lee, Yu-Mi; Sung, Tae-Yon; Chung, Ki-Wook; Yoon, Jong Ho; Hong, Suck Joon; Baek, Jung Hwan; Lee, Jeong Hyun; Kim, Tae Yong; Kim, Won Bae; Shong, Young Kee

    2016-07-01

    Detecting persistent/recurrent disease of medullary thyroid carcinoma (MTC) is important. The tumor-node-metastasis (TNM) staging system is useful for predicting disease-specific mortality, but is a static system and does not include postoperative serum calcitonin levels. We have focused on the clinical usefulness of dynamic risk stratification (DRS) using the best response to the initial therapy in MTC patients. A total of 120 MTC patients were classified into three DRS groups based on their responses to initial therapy. Clinical outcomes were assessed according to TNM staging and DRS. In the DRS, 70, 23 and 7 % of the MTC patients were classified into excellent, biochemical incomplete, or structural incomplete response groups, respectively. On TNM staging, 37, 16, 13 and 35 % of patients were stages I-IV, respectively. There were significant differences in survivals according to TNM staging (p = 0.03) and DRS (p = 0.005). During the median follow-up of 6.2 years, 75 patients (63 %) demonstrated no evidence of disease (NED). About 60 and 17 % of patients in stages III and IV were NED, respectively. DRS predicted NED better than TNM staging according to the proportion of variance explained (PVE) (49.1 vs. 28.7 %, respectively). At the final follow-up, 88, 4 and 0 % of patients in excellent, biochemical incomplete, and structural incomplete response groups attained NED, respectively. DRS based on the best response to the initial therapy can provide useful prognostic information in addition to initial TNM staging for predicting of mortality, as well as the likelihood of NED in MTC patients. PMID:26754662

  6. Gastric ulcers: malignancy yield and risk stratification for follow-up endoscopy

    PubMed Central

    Selinger, Christian P; Cochrane, Rebecca; Thanaraj, Sangeetha; Sainsbury, Anita; Subramanian, Venkat; Everett, Simon

    2016-01-01

    Background and study aim: Malignant change can occur in gastric ulcer but guideline recommendations for follow-endoscopy (FU-OGD) are conflicting. This study aims to determine rate of malignancy and need for follow-up for gastric ulcers. Patients and methods: Patients with a first diagnosis of gastric ulcer between January 2012 and September 2013 were studied by analyzing endoscopic assessments, dysplasia, and malignancy yield and the influence of risk factors on the likelihood of benign disease. Results: In a cohort of 432 patients with gastric ulcer (53 % male, mean age 65 years) dysplasia or neoplasia were found in 27 (19 adenocarcinomas, 2 cases of dysplasia, 5 lymphomas, 1 melanoma; malignancy yield 6 %). Twenty-five (93 %) cases were diagnosed on first biopsy. The cancer yield of FU-OGD after initially benign biopsy was 0.9 %. Binary logistic regression analysis revealed that endoscopically benign appearance (odds ratio 0.004 95 % CI 0 – 0.576; P = 0.029), benign histology on first biopsy (odds ratio 0 95 % CI 0 – 0.39; P = 0.011) and lower number of ulcers (odds ratio 0.22 (95 % CI 0.05 – 0.99); P = 0.049) were independent predictors of benign disease. All dysplastic and neoplastic cases would have been identified by a combination of initial biopsies plus repeat endoscopy with further biopsies for endoscopically suspicious appearances. Conclusions: In this large cohort 6 % of gastric ulcers were found to be malignant, highlighting the need for all gastric ulcers to be biopsied. The cancer yield of FU-OGD after benign biopsies was low. We have demonstrated that the combination of benign index histology and no endoscopic suspicion of malignancy can predict benign disease. We recommend that all gastric ulcers to be biopsied. Risk stratification could potentially reduce need for FU-OGD. PMID:27556082

  7. Adjuvant imatinib treatment in gastrointestinal stromal tumor: which risk stratification criteria and for how long? A case report.

    PubMed

    Blay, Jean-Yves; Levard, Alice

    2016-01-01

    Imatinib mesylate is approved for the adjuvant treatment of KIT-positive gastrointestinal stromal tumor (GIST) following surgical resection. However, uncertainty remains in terms of patient eligibility for adjuvant treatment and the optimal duration of treatment. Here, we present two challenging patient cases encountered in clinical practice that highlight the ambiguity in the current recommendations for adjuvant imatinib in GIST and discuss our approaches and rationales for treatment. The first case involves a 36-year-old man with a 7 cm duodenal GIST and possible tumor rupture during surgical resection. This patient's risk of GIST recurrence was either intermediate or high depending on which risk stratification criteria were used. The patient was treated with adjuvant imatinib for 3 years and experienced disease recurrence 14 months after the completion of treatment. Imatinib treatment was reintroduced, and the patient is in partial response 17 months later. The second case involves a 46-year-old woman at high risk of recurrence following surgical resection. Adjuvant treatment with imatinib was initiated. After considering the patient's initial high risk and good side-effect profile, the decision was made to continue adjuvant imatinib treatment for 5 years. As of May 2013, the patient has been receiving continuous imatinib treatment for 52 months, with no sign of progression. These reports exemplify the challenges faced in clinical practice because of uncertainties in optimal risk stratification criteria and duration of treatment. They stress the importance of individualized treatment and shared decision making between the physician and the patient. PMID:26457546

  8. Exploring the color feature power for psoriasis risk stratification and classification: A data mining paradigm.

    PubMed

    Shrivastava, Vimal K; Londhe, Narendra D; Sonawane, Rajendra S; Suri, Jasjit S

    2015-10-01

    A large percentage of dermatologist׳s decision in psoriasis disease assessment is based on color. The current computer-aided diagnosis systems for psoriasis risk stratification and classification lack the vigor of color paradigm. The paper presents an automated psoriasis computer-aided diagnosis (pCAD) system for classification of psoriasis skin images into psoriatic lesion and healthy skin, which solves the two major challenges: (i) fulfills the color feature requirements and (ii) selects the powerful dominant color features while retaining high classification accuracy. Fourteen color spaces are discovered for psoriasis disease analysis leading to 86 color features. The pCAD system is implemented in a support vector-based machine learning framework where the offline image data set is used for computing machine learning offline color machine learning parameters. These are then used for transformation of the online color features to predict the class labels for healthy vs. diseased cases. The above paradigm uses principal component analysis for color feature selection of dominant features, keeping the original color feature unaltered. Using the cross-validation protocol, the above machine learning protocol is compared against the standalone grayscale features with 60 features and against the combined grayscale and color feature set of 146. Using a fixed data size of 540 images with equal number of healthy and diseased, 10 fold cross-validation protocol, and SVM of polynomial kernel of type two, pCAD system shows an accuracy of 99.94% with sensitivity and specificity of 99.93% and 99.96%. Using a varying data size protocol, the mean classification accuracies for color, grayscale, and combined scenarios are: 92.85%, 93.83% and 93.99%, respectively. The reliability of the system in these three scenarios are: 94.42%, 97.39% and 96.00%, respectively. We conclude that pCAD system using color space alone is compatible to grayscale space or combined color and grayscale

  9. miRNA Expression Profiling Enables Risk Stratification in Archived and Fresh Neuroblastoma Tumor Samples

    PubMed Central

    De Preter, Katleen; Mestdagh, Pieter; Vermeulen, Joëlle; Zeka, Fjoralba; Naranjo, Arlene; Bray, Isabella; Castel, Victoria; Chen, Caifu; Drozynska, Elzbieta; Eggert, Angelika; Hogarty, Michael D.; Iżycka-Swieszewska, Ewa; London, Wendy B.; Noguera, Rosa; Piqueras, Marta; Bryan, Kenneth; Schowe, Benjamin; van Sluis, Peter; Molenaar, Jan J.; Schramm, Alexander; Schulte, Johannes H.; Stallings, Raymond L.; Versteeg, Rogier; Laureys, Geneviève; Van Roy, Nadine; Speleman, Frank; Vandesompele, Jo

    2012-01-01

    Purpose More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples. Experimental Design Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples. Results The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples. Conclusions In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material. PMID:22031095

  10. Value of Exercise ECG for Risk Stratification in Suspected or Known CAD in the Era of Advanced Imaging Technologies.

    PubMed

    Bourque, Jamieson M; Beller, George A

    2015-11-01

    Exercise stress electrocardiography (ExECG) is underutilized as the initial test modality in patients with interpretable electrocardiograms who are able to exercise. Although stress myocardial imaging techniques provide valuable diagnostic and prognostic information, variables derived from ExECG can yield substantial data for risk stratification, either supplementary to imaging variables or without concurrent imaging. In addition to exercise-induced ischemic ST-segment depression, such markers as ST-segment elevation in lead aVR, abnormal heart rate recovery post-exercise, failure to achieve target heart rate, and poor exercise capacity improve risk stratification of ExECG. For example, patients achieving ≥10 metabolic equivalents on ExECG have a very low prevalence of inducible ischemia and an excellent prognosis. In contrast, cardiac imaging techniques add diagnostic and prognostic value in higher-risk populations (e.g., poor functional capacity, diabetes, or chronic kidney disease). Optimal test selection for symptomatic patients with suspected coronary artery disease requires a patient-centered approach factoring in the risk/benefit ratio and cost-effectiveness. PMID:26563861

  11. Implantable Cardioverter-Defibrillators at End of Battery Life: Opportunities for Risk (Re)-Stratification in ICD Recipients.

    PubMed

    Merchant, Faisal M; Quest, Tammie; Leon, Angel R; El-Chami, Mikhael F

    2016-02-01

    Although implantable cardioverter-defibrillators (ICDs) are frequently viewed as a lifelong commitment in that patients are routinely scheduled for generator exchange (GE) at end of battery life, several considerations should prompt a reevaluation of risks and benefits before GE. Compared with initial ICD implant, patients receiving replacement devices are older, and have more comorbidities and shorter life expectancy, all of which may limit the benefit of ICD therapy following GE. Additionally, GE is associated with significant complications, including infection, which may increase the risk of mortality. In this paper, we review recent data regarding opportunities for risk stratification before GE, with a particular focus on those with improved left ventricular function and those who have not experienced ICD therapies during the first battery life. We also provide a broader perspective on ICD therapy, focusing on how decisions regarding GE may affect goals of care at the end of life. PMID:26821633

  12. Cardiac Health Risk Stratification System (CHRiSS): A Bayesian-Based Decision Support System for Left Ventricular Assist Device (LVAD) Therapy

    PubMed Central

    Loghmanpour, Natasha A.; Druzdzel, Marek J.; Antaki, James F.

    2014-01-01

    This study investigated the use of Bayesian Networks (BNs) for left ventricular assist device (LVAD) therapy; a treatment for end-stage heart failure that has been steadily growing in popularity over the past decade. Despite this growth, the number of LVAD implants performed annually remains a small fraction of the estimated population of patients who might benefit from this treatment. We believe that this demonstrates a need for an accurate stratification tool that can help identify LVAD candidates at the most appropriate point in the course of their disease. We derived BNs to predict mortality at five endpoints utilizing the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database: containing over 12,000 total enrolled patients from 153 hospital sites, collected since 2006 to the present day, and consisting of approximately 230 pre-implant clinical variables. Synthetic minority oversampling technique (SMOTE) was employed to address the uneven proportion of patients with negative outcomes and to improve the performance of the models. The resulting accuracy and area under the ROC curve (%) for predicted mortality were 30 day: 94.9 and 92.5; 90 day: 84.2 and 73.9; 6 month: 78.2 and 70.6; 1 year: 73.1 and 70.6; and 2 years: 71.4 and 70.8. To foster the translation of these models to clinical practice, they have been incorporated into a web-based application, the Cardiac Health Risk Stratification System (CHRiSS). As clinical experience with LVAD therapy continues to grow, and additional data is collected, we aim to continually update these BN models to improve their accuracy and maintain their relevance. Ongoing work also aims to extend the BN models to predict the risk of adverse events post-LVAD implant as additional factors for consideration in decision making. PMID:25397576

  13. Risk stratification for sudden cardiac death: current status and challenges for the future†

    PubMed Central

    Wellens, Hein J.J.; Schwartz, Peter J.; Lindemans, Fred W.; Buxton, Alfred E.; Goldberger, Jeffrey J.; Hohnloser, Stefan H.; Huikuri, Heikki V.; Kääb, Stefan; La Rovere, Maria Teresa; Malik, Marek; Myerburg, Robert J.; Simoons, Maarten L.; Swedberg, Karl; Tijssen, Jan; Voors, Adriaan A.; Wilde, Arthur A.

    2014-01-01

    Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds. PMID:24801071

  14. Risk stratification for sudden cardiac death: current status and challenges for the future.

    PubMed

    Wellens, Hein J J; Schwartz, Peter J; Lindemans, Fred W; Buxton, Alfred E; Goldberger, Jeffrey J; Hohnloser, Stefan H; Huikuri, Heikki V; Kääb, Stefan; La Rovere, Maria Teresa; Malik, Marek; Myerburg, Robert J; Simoons, Maarten L; Swedberg, Karl; Tijssen, Jan; Voors, Adriaan A; Wilde, Arthur A

    2014-07-01

    Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds. PMID:24801071

  15. Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis

    PubMed Central

    Yasuda, Masakazu; Iwanaga, Yoshitaka; Kato, Takao; Izumi, Toshiaki; Inuzuka, Yasutaka; Nakamura, Takashi; Miyaji, Yuki; Kawamura, Takayuki; Ikeguchi, Shigeru; Inoko, Moriaki; Kurita, Takashi; Miyazaki, Shunichi

    2016-01-01

    Background The presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes. Objective We aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI. Methods We included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded. Results Increased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal areas, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both. Conclusions In patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior/anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis. PMID:27547432

  16. Pain after total knee arthroplasty: a narrative review focusing on the stratification of patients at risk for persistent pain.

    PubMed

    Lavand'homme, P; Thienpont, E

    2015-10-01

    The patient with a painful arthritic knee awaiting total knee arthroplasty (TKA) requires a multidisciplinary approach. Optimal control of acute post-operative pain and the prevention of chronic persistent pain remains a challenge. The aim of this paper is to evaluate whether stratification of patients can help identify those who are at particular risk for severe acute or chronic pain. Intense acute post-operative pain, which is itself a risk factor for chronic pain, is more common in younger, obese female patients and those suffering from central pain sensitisation. Pre-operative pain, in the knee or elsewhere in the body, predisposes to central sensitisation. Pain due to osteoarthritis of the knee may also trigger neuropathic pain and may be associated with chronic medication like opioids, leading to a state of nociceptive sensitisation called 'opioid-induced hyperalgesia'. Finally, genetic and personality related risk factors may also put patients at a higher risk for the development of chronic pain. Those identified as at risk for chronic pain would benefit from specific peri-operative management including reduction in opioid intake pre-operatively, the peri-operative use of antihyperalgesic drugs such as ketamine and gabapentinoids, and a close post-operative follow-up in a dedicated chronic pain clinic. PMID:26430086

  17. Evidence-based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons learned from the US Armed Forces: Consensus and Future Directions

    PubMed Central

    Avital, Itzhak; Langan, Russell C.; Summers, Thomas A.; Steele, Scott R.; Waldman, Scott A.; Backman, Vadim; Yee, Judy; Nissan, Aviram; Young, Patrick; Womeldorph, Craig; Mancusco, Paul; Mueller, Renee; Noto, Khristian; Grundfest, Warren; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Eberhardt, John; Man, Yan Gao; Brücher, Björn LDM; Stojadinovic, Alexander

    2013-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. PMID:23459409

  18. MRI Risk Stratification for Tumor Relapse in Rectal Cancer Achieving Pathological Complete Remission after Neoadjuvant Chemoradiation Therapy and Curative Resection

    PubMed Central

    Kim, Honsoul; Myoung, Sungmin; Koom, Woong Sub; Kim, Nam Kyu; Kim, Myeong-Jin; Ahn, Joong Bae; Hur, Hyuk; Lim, Joon Seok

    2016-01-01

    Purpose Rectal cancer patients achieving pCR are known to have an excellent prognosis, yet no widely accepted consensus on risk stratification and post-operative management (e.g., adjuvant therapy) has been established. This study aimed to identify magnetic resonance imaging (MRI) high-risk factors for tumor relapse in pathological complete remission (pCR) achieved by rectal cancer patients who have undergone neoadjuvant concurrent chemoradiation therapy (CRT) and curative resection. Materials and Methods We analyzed 88 (male/female = 55/33, median age, 59.5 years [range 34–78]) pCR-proven rectal cancer patients who had undergone pre-CRT MRI, CRT, post-CRT MRI and curative surgery between July 2005 and December 2012. Patients were observed for post-operative tumor relapse. We analyzed the pre/post-CRT MRIs for parameters including mrT stage, mesorectal fascia (mrMRF) status, tumor volume, tumor regression grade (mrTRG), nodal status (mrN), and extramural vessel invasion (mrEMVI). We performed univariate analysis and Kaplan-Meier survival analysis. Results Post-operative tumor relapse occurred in seven patients (8.0%, n = 7/88) between 5.7 and 50.7 (median 16.8) months. No significant relevance was observed between tumor volume, volume reduction rate, mrTRG, mrT, or mrN status. Meanwhile, positive mrMRF (Ppre-CRT = 0.018, Ppre/post-CRT = 0.006) and mrEMVI (Ppre-CRT = 0.026, Ppre-/post-CRT = 0.008) were associated with higher incidence of post-operative tumor relapse. Kaplan-Meier survival analysis revealed a higher risk of tumor relapse in patients with positive mrMRF (Ppre-CRT = 0.029, Ppre-/post-CRT = 0.009) or mrEMVI (Ppre-CRT = 0.024, Ppre-/post-CRT = 0.003). Conclusion Positive mrMRF and mrEMVI status was associated with a higher risk of post-operative tumor relapse of pCR achieved by rectal cancer patients, and therefore, can be applied for risk stratification and to individualize treatment plans. PMID:26730717

  19. The use of molecular-based risk stratification and pharmacogenomics for outcome prediction and personalized therapeutic management of multiple myeloma

    PubMed Central

    Johnson, Sarah K.; Heuck, Christoph J.; Albino, Anthony P.; Qu, Pingping; Zhang, Qing; Barlogie, Bart

    2015-01-01

    Despite improvement in therapeutic efficacy, multiple myeloma (MM) remains incurable with a median survival of approximately 10 years. Gene-expression profiling (GEP) can be used to elucidate the molecular basis for resistance to chemotherapy through global assessment of molecular alterations that exist at diagnosis, after therapeutic treatment and that evolve during tumor progression. Unique GEP signatures associated with recurrent chromosomal translocations and ploidy changes have defined molecular classes with differing clinical features and outcomes. When compared to other stratification systems the GEP70 test remained a significant predictor of outcome, reduced the number of patients classified with a poor prognosis, and identified patients at increased risk of relapse despite their standard clinico-pathologic and genetic findings. GEP studies of serial samples showed that risk increases over time, with relapsed disease showing GEP shifts toward a signature of poor outcomes. GEP signatures of myeloma cells after therapy were prognostic for event-free and overall survival and thus may be used to identify novel strategies for overcoming drug resistance. This brief review will focus on the use of GEP of MM to define high-risk myeloma, and elucidate underlying mechanisms that are beginning to change clinical decision-making and inform drug design. PMID:22002477

  20. Outcome Predictors in Prosthetic Joint Infections--Validation of a risk stratification score for Prosthetic Joint Infections in 120 cases.

    PubMed

    Wimmer, Matthias D; Randau, Thomas M; Friedrich, Max J; Ploeger, Milena M; Schmolder, Jan; Strauss, Andreas C; Pennekamp, Peter H; Vavken, Patrick; Gravius, Sascha

    2016-03-01

    Prosthetic joint infections are a major challenge in total joint arthroplasty, especially in times of accumulating drug resistancies. Even though predictive risk classifications are a widely accepted tool to define a suitable treatment protocol a classification is still missing considering the difficulty in treating the -causative pathogen antibiotically. In this study, we present and evaluate a new predictive risk stratification for prosthetic joint infections in 120 cases, treated with a two-stage exchange. Treatment outcomes in 120 patients with proven prosthetic joint infections in hip and knee prostheses were regressed on time of infection, systemic risk factors, local risk factors and the difficulty in treating the causing pathogen. The main outcome variable was "definitely free of infection" after two years as published. Age, gender, and BMI were included as covariables and analyzed in a logistic regression model. 66 male and 54 female patients, with a mean age at surgery of 68.3 years±12.0 and a mean BMI of 26.05±6.21 were included in our survey and followed for 29.0±11.3 months. We found a significant association (p<0.001) between our score and the outcome parameters evaluated. Age, gender and BMI did not show a significant association with the outcome. These results show that our score is an independent and reliable predictor for the cure rate in prosthetic joint infections in hip and knee prostheses treated within a two-stage exchange protocol. Our score illustrates, that there is a statistically significant, sizable decrease in cure rate with an increase in score. In patients with prosthetic joint infections the validation of a risk score may help to identify patients with local and systemic risk factors or with infectious organisms identified as "difficult to treat" prior to the treatment or the decision about the treatment concept. Thus, appropriate extra care should be considered and provided. PMID:26984667

  1. Risk stratification and rapid geriatric screening in an emergency department – a quasi-randomised controlled trial

    PubMed Central

    2014-01-01

    Background To determine if risk stratification followed by rapid geriatric screening in an emergency department (ED) reduced functional decline, ED reattendance and hospitalisation. Method This was a quasi-randomised controlled trial. Patients were randomised by the last digit of their national registration identity card (NRIC). Odd number controls received standard ED care; even number patients received geriatric screening, followed by intervention and/or onward referrals. Patients were followed up for 12 months. Results There were 500 and 280 patients in the control and intervention groups. The intervention group had higher Triage Risk Screening Tool (TRST) scores (34.3% vs 25.4% TRST ≥3, p = 0.01) and lower baseline Instrumental Activity of Daily Living (IADL) scores (22.84 vs 24.18, p < 0.01). 82.9% of the intervention group had unmet needs; 62.1% accepted our interventions. Common positive findings were fall risk (65.0%), vision (61.4%), and footwear (58.2%). 28.2% were referred to a geriatric clinic and 11.8% were admitted. 425 (85.0%) controls and 234 (83.6%) in the intervention group completed their follow-up. After adjusting for TRST and baseline IADL, the intervention group had significant preservation in function (Basic ADL -0.99 vs -0.24, p < 0.01; IADL -2.57 vs +0.45, p < 0.01) at 12 months. The reduction in ED reattendance (OR0.75, CI 0.55-1.03, p = 0.07) and hospitalization (OR0.77, CI0.57-1.04, p = 0.09) were not significant, however the real difference would have been wider as 21.2% of the control group received geriatric screening at the request of the ED doctor. A major limitation was that a large proportion of patients who were randomized to the intervention group either refused (18.8%) or left the ED before being approached (32.0%). These two groups were not followed up, and hence were excluded in our analysis. Conclusion Risk stratification and focused geriatric screening in ED resulted in significant preservation

  2. Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

    SciTech Connect

    Koontz, Bridget F.; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W. Robert

    2012-01-01

    Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.

  3. Risk stratification in perforated duodenal ulcers. A prospective validation of predictive factors.

    PubMed Central

    Boey, J; Choi, S K; Poon, A; Alagaratnam, T T

    1987-01-01

    In order to validate a previously derived set of risk factors, 259 consecutive patients who had simple closure or definitive operation for perforated duodenal ulcers were studied prospectively. Major medical illness, preoperative shock, and longstanding perforation (more than 24 hours) correctly predicted the outcome in 93.8% of patients. Most importantly, 16 patients (6.2%) who died after operation could be identified (no false-negative error). The mortality rate increased progressively with increasing numbers of risk factors: 0%, 10%, 45.5%, and 100% in patients with none, one, two, and all three risk factors, respectively. These findings underscore the importance of patient selection and the feasibility of a risk grading system in guiding surgical management. Definitive surgery can be done safely in good-risk patients. Simple closure is preferable in those patients with uncomplicated perforations if any risk factor is present. Truncal vagotomy and drainage may be required if there is coexisting bleeding or stenosis. Nonoperative treatment deserves re-evaluation in patients with all three risk factors because of their uniformly dismal outcome after operation. PMID:3800459

  4. New Cardiovascular Risk Factors and Their Use for an Accurate Cardiovascular Risk Assessment in Hypertensive Patients

    PubMed Central

    TAUTU, Oana-Florentina; DARABONT, Roxana; ONCIUL, Sebastian; DEACONU, Alexandru; COMANESCU, Ioana; ANDREI, Radu Dan; DRAGOESCU, Bogdan; CINTEZA, Mircea; DOROBANTU, Maria

    2014-01-01

    Objectives: To analyze the predictive value of new cardiovascular (CV) risk factors for CV risk assessment in the adult Romanian hypertensive (HT) population. Methods: Hypertensive adults aged between 40-65 years of age, identified in national representative SEPHAR II survey were evaluated by anthropometric, BP and arterial stiffness measurements: aortic pulse wave velocity (PWVao), aortic augmentation index (AIXao), revers time (RT) and central systolic blood pressure (SBPao), 12 lead ECGs and laboratory workup. Values above the 4th quartile of mean SBP' standard deviation (s.d.) defined increased BP variability. Log(TG/HDL-cholesterol) defined atherogenic index of plasma (AIP). Serum uric acid levels above 5.70 mg/dl for women and 7.0 mg/dl for males defined hyperuricemia (HUA). CV risk was assessed based on SCORE chart for high CV risk countries. Binary logistic regression using a stepwise likelihood ratio method (adjustments for major confounders and colliniarity analysis) was used in order to validate predictors of high and very high CV risk class. Results: The mean SBP value of the study group was 148.46±19.61 mmHg. Over forty percent of hypertensives had a high and very high CV risk. Predictors of high/very high CV risk category validated by regression analysis were: increased visit-to-visit BP variability (OR: 2.49; 95%CI: 1.67-3.73), PWVao (OR: 1.12; 95%CI: 1.02-1.22), RT (OR: 0.95; 95% CI: 0.93-0.98), SBPao (OR: 1.01; 95%CI: 1.01-1.03) and AIP (OR: 7.08; 95%CI: 3.91-12.82). Conclusion: The results of our study suggests that the new CV risk factors such as increased BP variability, arterial stiffness indices and AIP are useful tools for a more accurate identification of hypertensives patients at high and very high CV risk. PMID:25705267

  5. An Official American Thoracic Society Clinical Practice Guideline: Diagnosis, Risk Stratification, and Management of Pulmonary Hypertension of Sickle Cell Disease

    PubMed Central

    Klings, Elizabeth S.; Machado, Roberto F.; Barst, Robyn J.; Morris, Claudia R.; Mubarak, Kamal K.; Gordeuk, Victor R.; Kato, Gregory J.; Ataga, Kenneth I.; Gibbs, J. Simon; Castro, Oswaldo; Rosenzweig, Erika B.; Sood, Namita; Hsu, Lewis; Wilson, Kevin C.; Telen, Marilyn J.; DeCastro, Laura M.; Krishnamurti, Lakshmanan; Steinberg, Martin H.; Badesch, David B.; Gladwin, Mark T.

    2014-01-01

    Background: In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro–brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality. Methods: A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations. Target audiences include all clinicians who take care of patients with SCD. Results: Mortality risk stratification guides decision making. An increased risk for mortality is defined as a TRV equal to or greater than 2.5 m/second, an NT-pro-BNP level equal to or greater than 160 pg/ml, or RHC-confirmed PH. For patients identified as having increased mortality risk, we make a strong recommendation for hydroxyurea as first-line therapy and a weak recommendation for chronic transfusions as an alternative therapy. For all patients with SCD with elevated TRV alone or elevated NT-pro-BNP alone, and for patients with SCD with RHC-confirmed PH with elevated pulmonary artery wedge pressure and low pulmonary vascular resistance, we make a strong recommendation against PAH-specific therapy. However, for select patients with SCD with RHC-confirmed PH who have elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure, we make a weak recommendation for either prostacyclin agonist or endothelin receptor antagonist therapy and a strong recommendation against phosphodiesterase-5 inhibitor therapy. Conclusions: Evidence-based recommendations for the management of patients with SCD with increased mortality risk are provided, but will require frequent reassessment and updating. PMID:24628312

  6. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models.

    PubMed

    Arevalo, Hermenegild J; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C; Trayanova, Natalia A

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  7. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models

    PubMed Central

    Arevalo, Hermenegild J.; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C.; Trayanova, Natalia A.

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  8. The role of early 18F-FDG PET/CT in therapeutic management and ongoing risk stratification of high/intermediate-risk thyroid carcinoma.

    PubMed

    Triviño Ibáñez, E M; Muros, M A; Torres Vela, E; Llamas Elvira, J M

    2016-03-01

    Little is known about the role in ongoing risk stratification of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed early after radioactive iodine (RAI) ablation in differentiated thyroid carcinoma (DTC). The aim of the study is to investigate whether 18F-FDG PET/CT performed early after RAI ablation is useful to detect disease and to influence therapy and ongoing risk stratification. Patients with high/intermediate risk of recurrent DTC were included. 18F-FDG PET/CT scan was performed within 6 months after RAI ablation. We confirmed results with other imaging techniques, pathology reports, or follow-up. We classified the patient response as excellent, acceptable, or incomplete. Modified Hicks criteria were used to evaluate clinical impact. We included 81 patients with high/intermediate risk of recurrent DTC. Forty-one (50.6 %) had positive uptake in 18F-FDG PET/CT, with negative (131)I whole-body scan ((131)I WBS). Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT were 92.5, 90.2, and 91.4 %, respectively. 18F-FDG PET/CT results had an impact on therapy in 38.3 % of patients. One year after initial therapy, 45.7 % showed excellent response, 8.6 % acceptable response, and 45.7 % incomplete response. A statistically significant relationship was found between negative 18F-FDG PET/CT and excellent response (80 vs. 12.2 %, p < 0.001; OR 52.8). 18F-FDG PET/CT scan performed early in surveillance of patients with high/intermediate-risk thyroid carcinoma provides important additional information not available with conventional follow-up methods and had a high impact on therapy. A negative 18F-FDG PET/CT predicts an excellent response to therapy in the new ongoing risk stratification. PMID:26224589

  9. Public health implications from COGS and potential for risk stratification and screening.

    PubMed

    Burton, Hilary; Chowdhury, Susmita; Dent, Tom; Hall, Alison; Pashayan, Nora; Pharoah, Paul

    2013-04-01

    The PHG Foundation led a multidisciplinary program, which used results from COGS research identifying genetic variants associated with breast, ovarian and prostate cancers to model risk-stratified prevention for breast and prostate cancers. Implementing such strategies would require attention to the use and storage of genetic information, the development of risk assessment tools, new protocols for consent and programs of professional education and public engagement. PMID:23535723

  10. Performance of 2014 NICE defibrillator implantation guidelines in heart failure risk stratification

    PubMed Central

    Cubbon, Richard M; Witte, Klaus K; Kearney, Lorraine C; Gierula, John; Byrom, Rowenna; Paton, Maria; Sengupta, Anshuman; Patel, Peysh A; MN Walker, Andrew; Cairns, David A; Rajwani, Adil; Hall, Alistair S; Sapsford, Robert J; Kearney, Mark T

    2016-01-01

    Objective Define the real-world performance of recently updated National Institute for Health and Care Excellence guidelines (TA314) on implantable cardioverter-defibrillator (ICD) use in people with chronic heart failure. Methods Multicentre prospective cohort study of 1026 patients with stable chronic heart failure, associated with left ventricular ejection fraction (LVEF) ≤45% recruited in cardiology outpatient departments of four UK hospitals. We assessed the capacity of TA314 to identify patients at increased risk of sudden cardiac death (SCD) or appropriate ICD shock. Results The overall risk of SCD or appropriate ICD shock was 2.1 events per 100 patient-years (95% CI 1.7 to 2.6). Patients meeting TA314 ICD criteria (31.1%) were 2.5-fold (95% CI 1.6 to 3.9) more likely to suffer SCD or appropriate ICD shock; they were also 1.5-fold (95% CI 1.1 to 2.2) more likely to die from non-cardiovascular causes and 1.6-fold (95% CI 1.1 to 2.3) more likely to die from progressive heart failure. Patients with diabetes not meeting TA314 criteria experienced comparable absolute risk of SCD or appropriate ICD shock to patients without diabetes who met TA314 criteria. Patients with ischaemic cardiomyopathy not meeting TA314 criteria experienced comparable absolute risk of SCD or appropriate ICD shock to patients with non-ischaemic cardiomyopathy who met TA314 criteria. Conclusions TA314 can identify patients with reduced LVEF who are at increased relative risk of sudden death. Clinicians should also consider clinical context and the absolute risk of SCD when advising patients about the potential risks and benefits of ICD therapy. PMID:26857212

  11. Developing and evaluating an automated appendicitis risk stratification algorithm for pediatric patients in the emergency department

    PubMed Central

    Deleger, Louise; Brodzinski, Holly; Zhai, Haijun; Li, Qi; Lingren, Todd; Kirkendall, Eric S; Alessandrini, Evaline; Solti, Imre

    2013-01-01

    Objective To evaluate a proposed natural language processing (NLP) and machine-learning based automated method to risk stratify abdominal pain patients by analyzing the content of the electronic health record (EHR). Methods We analyzed the EHRs of a random sample of 2100 pediatric emergency department (ED) patients with abdominal pain, including all with a final diagnosis of appendicitis. We developed an automated system to extract relevant elements from ED physician notes and lab values and to automatically assign a risk category for acute appendicitis (high, equivocal, or low), based on the Pediatric Appendicitis Score. We evaluated the performance of the system against a manually created gold standard (chart reviews by ED physicians) for recall, specificity, and precision. Results The system achieved an average F-measure of 0.867 (0.869 recall and 0.863 precision) for risk classification, which was comparable to physician experts. Recall/precision were 0.897/0.952 in the low-risk category, 0.855/0.886 in the high-risk category, and 0.854/0.766 in the equivocal-risk category. The information that the system required as input to achieve high F-measure was available within the first 4 h of the ED visit. Conclusions Automated appendicitis risk categorization based on EHR content, including information from clinical notes, shows comparable performance to physician chart reviewers as measured by their inter-annotator agreement and represents a promising new approach for computerized decision support to promote application of evidence-based medicine at the point of care. PMID:24130231

  12. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management.

    PubMed

    Rajkumar, S Vincent

    2016-07-01

    Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Patients with del(17p), t(14;16), and t(14;20) have high-risk multiple myeloma. Patients with t(4;14) translocation and gain(1q) have intermediate-risk. All others are considered standard-risk. Initial treatment consists of bortezomib, lenalidomide, dexamethasone (VRD). In high-risk patients, carfilzomib, lenalidomide, dexamethasone (KRD) is an alternative to VRD. In eligible patients, initial therapy is given for approximately 3-4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT at first relapse. Patients not candidates for transplant are treated with Rd until progression, or alternatively, a triplet regimen such as VRD for approximately 12-18 months. After ASCT, lenalidomide maintenance is considered for standard risk patients especially in those who are not in very good partial response or better, while maintenance with a bortezomib-based regimen is needed for patients with intermediate or high-risk disease. Patients with indolent relapse can be treated with 2-drug or 3-drug combinations. Patients with more aggressive relapse require a triplet regimen or a combination of multiple active agents. Am. J. Hematol. 91:720-734, 2016. © 2016 Wiley Periodicals, Inc. PMID:27291302

  13. Sudden Cardiac Risk Stratification with Electrocardiographic Indices - A Review on Computational Processing, Technology Transfer, and Scientific Evidence.

    PubMed

    Gimeno-Blanes, Francisco J; Blanco-Velasco, Manuel; Barquero-Pérez, Óscar; García-Alberola, Arcadi; Rojo-Álvarez, José L

    2016-01-01

    Great effort has been devoted in recent years to the development of sudden cardiac risk predictors as a function of electric cardiac signals, mainly obtained from the electrocardiogram (ECG) analysis. But these prediction techniques are still seldom used in clinical practice, partly due to its limited diagnostic accuracy and to the lack of consensus about the appropriate computational signal processing implementation. This paper addresses a three-fold approach, based on ECG indices, to structure this review on sudden cardiac risk stratification. First, throughout the computational techniques that had been widely proposed for obtaining these indices in technical literature. Second, over the scientific evidence, that although is supported by observational clinical studies, they are not always representative enough. And third, via the limited technology transfer of academy-accepted algorithms, requiring further meditation for future systems. We focus on three families of ECG derived indices which are tackled from the aforementioned viewpoints, namely, heart rate turbulence (HRT), heart rate variability (HRV), and T-wave alternans. In terms of computational algorithms, we still need clearer scientific evidence, standardizing, and benchmarking, siting on advanced algorithms applied over large and representative datasets. New scenarios like electronic health recordings, big data, long-term monitoring, and cloud databases, will eventually open new frameworks to foresee suitable new paradigms in the near future. PMID:27014083

  14. Sudden Cardiac Risk Stratification with Electrocardiographic Indices - A Review on Computational Processing, Technology Transfer, and Scientific Evidence

    PubMed Central

    Gimeno-Blanes, Francisco J.; Blanco-Velasco, Manuel; Barquero-Pérez, Óscar; García-Alberola, Arcadi; Rojo-Álvarez, José L.

    2016-01-01

    Great effort has been devoted in recent years to the development of sudden cardiac risk predictors as a function of electric cardiac signals, mainly obtained from the electrocardiogram (ECG) analysis. But these prediction techniques are still seldom used in clinical practice, partly due to its limited diagnostic accuracy and to the lack of consensus about the appropriate computational signal processing implementation. This paper addresses a three-fold approach, based on ECG indices, to structure this review on sudden cardiac risk stratification. First, throughout the computational techniques that had been widely proposed for obtaining these indices in technical literature. Second, over the scientific evidence, that although is supported by observational clinical studies, they are not always representative enough. And third, via the limited technology transfer of academy-accepted algorithms, requiring further meditation for future systems. We focus on three families of ECG derived indices which are tackled from the aforementioned viewpoints, namely, heart rate turbulence (HRT), heart rate variability (HRV), and T-wave alternans. In terms of computational algorithms, we still need clearer scientific evidence, standardizing, and benchmarking, siting on advanced algorithms applied over large and representative datasets. New scenarios like electronic health recordings, big data, long-term monitoring, and cloud databases, will eventually open new frameworks to foresee suitable new paradigms in the near future. PMID:27014083

  15. Intensity of Left Atrial Spontaneous Echo Contrast as a Correlate for Stroke Risk Stratification in Patients with Nonvalvular Atrial Fibrillation

    PubMed Central

    Zhao, Yuanping; Ji, Lijing; Liu, Jian; Wu, Juefei; Wang, Yan; Shen, Shuxin; Guo, Shengcun; Jian, Rong; Chen, Gangbin; Wei, Xuan; Liao, Wangjun; Kutty, Shelby; Liao, Yulin; Bin, Jianping

    2016-01-01

    The intensity of left atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography (TEE) has been proposed as an important variable in the stratification of thromboembolic risk, particularly in patients with nonvalvular atrial fibrillation (NVAF). We hypothesized that the quantification of LASEC by ultrasound will improve its utility in predicting subsequent stroke events in patients with NVAF. Patients (n = 206) with definite NVAF receiving TEE were included for this prospective cohort study. Baseline clinical risk factors of stroke, CHADS2 score and CHA2DS2-Vasc, left atrial thrombus (LAT), the five-grades of LASEC and video intensity (VI) value of LASEC were measured. During 2 years follow-up, 20 patients (9.7%) developed stroke. VI value of LASEC in the patients with stroke was higher compared to patients without stroke (25.30 ± 3.61 vs. 8.65 ± 0.81, p < 0.001). On logistic regression analysis, LAT, qualitative LASEC, graded LASEC, VI value of LASEC and CHADS2 and CHA2DS2-Vasc score were independent predictors of stroke. Among them, the highest area under the curve of receiver operating characteristic (ROC) in predicting stroke was VI value of LASEC (p < 0.05). These results show that quantification of LASEC by VI value is the most favorable predictor of stroke in patients with NVAF, and calls for improving the utility of LASEC in predicting subsequent stroke events. PMID:27277939

  16. Intensity of Left Atrial Spontaneous Echo Contrast as a Correlate for Stroke Risk Stratification in Patients with Nonvalvular Atrial Fibrillation.

    PubMed

    Zhao, Yuanping; Ji, Lijing; Liu, Jian; Wu, Juefei; Wang, Yan; Shen, Shuxin; Guo, Shengcun; Jian, Rong; Chen, Gangbin; Wei, Xuan; Liao, Wangjun; Kutty, Shelby; Liao, Yulin; Bin, Jianping

    2016-01-01

    The intensity of left atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography (TEE) has been proposed as an important variable in the stratification of thromboembolic risk, particularly in patients with nonvalvular atrial fibrillation (NVAF). We hypothesized that the quantification of LASEC by ultrasound will improve its utility in predicting subsequent stroke events in patients with NVAF. Patients (n = 206) with definite NVAF receiving TEE were included for this prospective cohort study. Baseline clinical risk factors of stroke, CHADS2 score and CHA2DS2-Vasc, left atrial thrombus (LAT), the five-grades of LASEC and video intensity (VI) value of LASEC were measured. During 2 years follow-up, 20 patients (9.7%) developed stroke. VI value of LASEC in the patients with stroke was higher compared to patients without stroke (25.30 ± 3.61 vs. 8.65 ± 0.81, p < 0.001). On logistic regression analysis, LAT, qualitative LASEC, graded LASEC, VI value of LASEC and CHADS2 and CHA2DS2-Vasc score were independent predictors of stroke. Among them, the highest area under the curve of receiver operating characteristic (ROC) in predicting stroke was VI value of LASEC (p < 0.05). These results show that quantification of LASEC by VI value is the most favorable predictor of stroke in patients with NVAF, and calls for improving the utility of LASEC in predicting subsequent stroke events. PMID:27277939

  17. Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications

    SciTech Connect

    Waxweiler, Timothy V.; Rusthoven, Chad G.; Proper, Michelle S.; Cost, Carrye R.; Cost, Nicholas G.; Donaldson, Nathan; Garrington, Timothy; Greffe, Brian S.; Heare, Travis; Macy, Margaret E.; Liu, Arthur K.

    2015-06-01

    Purpose: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those <20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics. Methods and Materials: From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex, year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk. Results: A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P<.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P<.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P<.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P<.001). Conclusions: The current COG risk group

  18. Frailty and cardiovascular disease: potential role of gait speed in surgical risk stratification in older adults

    PubMed Central

    Chen, Michael A.

    2015-01-01

    Frailty is a state of late life decline and vulnerability, typified by physical weakness and decreased physiologic reserve. The epidemiology and pathophysiology of frailty share features with those of cardiovascular disease. Gait speed can be used as a measure of frailty and is a powerful predictor of mortality. Advancing age is a potent risk factor for cardiovascular disease and has been associated with an increased risk of adverse outcomes. Older adults comprise approximately half of cardiac surgery patients, and account for nearly 80% of the major complications and deaths following surgery. The ability of traditional risk models to predict mortality and major morbidity in older patients being considered for cardiac surgery may improve if frailty, as measured by gait speed, is included in their assessment. It is possible that in the future frailty assessment may assist in choosing among therapies (e.g., surgical vs. percutaneous aortic valve replacement for patients with aortic stenosis). PMID:25678904

  19. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use.

    PubMed

    Kraus, V B; Blanco, F J; Englund, M; Karsdal, M A; Lohmander, L S

    2015-08-01

    Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of OA Development) and ROAP (Risk of OA Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages - REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools. PMID:25865392

  20. Diagnosis, risk stratification and management of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

    PubMed

    van de Donk, N W C J; Mutis, T; Poddighe, P J; Lokhorst, H M; Zweegman, S

    2016-05-01

    Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders. IgG and IgA MGUS are precursor conditions of multiple myeloma (MM), whereas light-chain MGUS is a precursor condition of light-chain MM. Smoldering MM (SMM) is a precursor condition with higher tumor burden and higher risk of progression to symptomatic MM compared to MGUS. Assessment of the risk of progression of patients with asymptomatic monoclonal gammopathies is based on various factors including clonal burden, as well as biological characteristics, such as cytogenetic abnormalities and light-chain production. Several models have been constructed that are useful in daily practice for predicting risk of progression of MGUS or SMM. Importantly, the plasma cell clone may occasionally be responsible for severe organ damage through the production of a M-protein which deposits in tissues or has autoantibody activity. These disorders are rare and often require therapy directed at eradication of the underlying clone. Importantly, recent studies have shown that asymptomatic patients with a bone marrow plasma cell percentage ≥60%, free light-chain ratio ≥100, or >1 focal lesion on MRI (myeloma-defining events) have a 80% risk of developing symptomatic MM within 2 years. These patients are now considered to have MM requiring therapy, similar to patients with symptomatic disease. In this review, we provide an overview of the new diagnostic criteria of the monoclonal gammopathies and discuss risk of progression to active MM. We also provide recommendations for the management of patients with MGUS and SMM including risk-adapted follow-up. PMID:27161311

  1. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy.

    PubMed

    Maron, Barry J; Maron, Martin S

    2016-05-01

    Hypertrophic cardiomyopathy (HCM) is regarded as the most common nontraumatic cause of sudden death (SD) in young people (including trained athletes). Introduction of implantable cardioverter-defibrillators (ICD) to HCM 15 years ago represented a new paradigm for clinical practice and probably the most significant advance in management of this disease. ICDs offer protection against SD by terminating potentially lethal ventricular tachyarrhythmias (11%/year secondary and 4%/year primary prevention), although implant decisions are weighed against the possibility of device-related complications (5%/year). ICDs have altered the natural history of HCM, creating the opportunity for extended or normal longevity for many patients. However, assessing SD risk and targeting appropriate candidates for prophylactic device therapy can be compounded by unpredictability of the underlying arrhythmogenic substrate, evident by delays ≥10 years between implant and first ICD intervention. Multiple or a single strong risk marker within the clinical profile of an individual HCM patient can justify consideration for a primary-prevention ICD when combined with physician judgment and shared decision making. The role of the mathematical SD risk score proposed by the European Society of Cardiology to identify patients who benefit from ICD therapy is incompletely resolved. Contemporary treatment interventions and advanced risk stratification using ≥1 conventional markers have served the HCM patient population well, with reduced disease-related mortality rates across all age groups to <1%/year, due largely to the penetration of ICDs into HCM practice. Prevention of SD has now become an integral, albeit challenging, component of HCM management, contributing importantly to its emergence as a contemporary treatable cardiac disease. PMID:26749314

  2. Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations.

    PubMed

    Hansen, T W; Thijs, L; Li, Y; Boggia, J; Liu, Y; Asayama, K; Kikuya, M; Björklund-Bodegård, K; Ohkubo, T; Jeppesen, J; Torp-Pedersen, C; Dolan, E; Kuznetsova, T; Stolarz-Skrzypek, K; Tikhonoff, V; Malyutina, S; Casiglia, E; Nikitin, Y; Lind, L; Sandoya, E; Kawecka-Jaszcz, K; Filipovský, J; Imai, Y; Wang, J; O'Brien, E; Staessen, J A

    2014-09-01

    Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI. PMID:24430701

  3. Usefulness of semiquantitative analysis of dipyridamole-thallium-201 redistribution for improving risk stratification before vascular surgery

    SciTech Connect

    Levinson, J.R.; Boucher, C.A.; Coley, C.M.; Guiney, T.E.; Strauss, H.W.; Eagle, K.A. )

    1990-08-15

    Preoperative dipyridamole-thallium-201 scanning is sensitive in identifying patients prone to ischemic cardiac complications after vascular surgery, but most patients with redistribution do not have an event after surgery. Therefore, its positive predictive value is limited. To determine which patients with thallium redistribution are at highest risk, dipyridamole-thallium-201 images were interpreted semiquantitatively. Sixty-two consecutive patients with redistribution on preoperative dipyridamole-thallium-201 planar imaging studies were identified. Each thallium scan was then analyzed independently by 2 observers for the number of myocardial segments out of 15, the number of thallium views out of 3 and the number of coronary artery territories with redistribution. Seventeen patients (27%) had postoperative ischemic events, including unstable angina pectoris, ischemic pulmonary edema, myocardial infarction and cardiac death. Thallium predictors of ischemic operative complications included thallium redistribution greater than or equal to 4 myocardial segments (p = 0.03), greater than or equal to 2 of the 3 planar views (p = 0.005) and greater than or equal to 2 coronary territories (p = 0.007). No patient with redistribution in only 1 view had an ischemic event (0 of 15). Thus, determining the extent of redistribution by dipyridamole-thallium-201 scanning improves risk stratification before vascular surgery. Patients with greater numbers of myocardial segments and greater numbers of coronary territories showing thallium-201 redistribution are at higher risk for ischemic cardiac complications. In contrast, when the extent of thallium redistribution is limited, there is a lower risk despite the presence of redistribution.

  4. Adrenomedullin for Risk Stratification of Emergency Patients With Nonspecific Complaints: An Interventional Multicenter Pilot Study.

    PubMed

    Nickel, Christian Hans; Messmer, Anna Sarah; Ghanim, Leyla; Ilsemann-Karakoumis, Julia; Giersdorf, Sven; Hertel, Sabine; Ernst, Susanne; Geigy, Nicolas; Bingisser, Roland

    2016-01-01

    Patients with nonspecific complaints (NSC) presenting to the emergency department (ED) are at risk of life-threatening conditions. New stress biomarkers such as the midregional portion of adrenomedullin (MR-proADM) promise to support decision-making. This study tested the following hypotheses: biomarker-assisted disposition of patients with NSC will not increase mortality. Second, discharge from the ED will increase if clinical risk assessment is combined with low MR-proADM levels. Third, inappropriate disposition to a lower level of care will decrease, if clinical assessment is combined with high MR-proADM levels, and fourth that this algorithm is feasible in the ED setting. Prospective, multicenter, randomized, controlled interventional feasibility study with a 30-day follow-up, including patients with NSC. Patients were randomly assigned to either the standard group (decision-making solely based on clinical assessment) or the Novum group (biomarker-assisted). Regarding disposition, patients were assigned to 1 of 3 risk classes: high-risk (admission to hospital), intermediate risk (community geriatric hospital), and low-risk patients (discharge). In the Novum group, in addition to clinical risk assessment, the information of the MR-proADM level was used. Unless there were overruling criteria, patients were transferred or discharged according to the risk assessment. Primary endpoint was 30-day mortality. Secondary endpoints were comparisons of patient disposition and related mortality rates, ED, and hospital length of stay and readmission. The final study cohort consisted of 398 patients (210 in the Standard group and 188 in the Novum group). Overruling, that is, disposition not according to the result of the proposed algorithm occurred in 51 cases. Baseline characteristics between Standard and Novum groups were similar. The mortality rate in the Novum group was 4.3%, as compared to the Standard group mortality of 6.2%, which was not significantly different

  5. Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group

    PubMed Central

    McGuigan, C; Craner, M; Guadagno, J; Kapoor, R; Mazibrada, G; Molyneux, P; Nicholas, R; Palace, J; Pearson, O R; Rog, D; Young, C A

    2016-01-01

    The use of natalizumab for highly active relapsing-remitting multiple sclerosis (MS) is influenced by the occurrence of progressive multifocal leukoencephalopathy (PML). Through measurement of the anti-JCV antibody index, and in combination with the presence or absence of other known risk factors, it may be possible to stratify patients with MS according to their risk of developing PML during treatment with natalizumab and detect early suspected PML using MRI including a diffusion-weighted imaging sequence. This paper describes a practical consensus guideline for treating neurologists, based on current evidence, for the introduction into routine clinical practice of anti-JCV antibody index testing of immunosuppressant-naïve patients with MS, either currently being treated with, or initiating, natalizumab, based on their anti-JCV antibody status. Recommendations for the frequency and type of MRI screening in patients with varying index-associated PML risks are also discussed. This consensus paper presents a simple and pragmatic algorithm to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk. PMID:26492930

  6. Coronary computer tomographic angiography for preoperative risk stratification in patients undergoing liver transplantation.

    PubMed

    Jodocy, Daniel; Abbrederis, Susanne; Graziadei, Ivo W; Vogel, Wolfgang; Pachinger, Otmar; Feuchtner, Gudrun M; Jaschke, Werner; Friedrich, Guy

    2012-09-01

    The assessment of the cardiovascular risk profile in patients with end-stage liver disease is essential prior to liver transplantation (LT) as cardiovascular diseases are major causes of morbidity and mortality in the posttransplant course. The aim of this study was to evaluate the accuracy of a 64-slice coronary computed tomographic angiography (CTA) and coronary calcium scoring (CCS) to predict the postoperative cardiovascular risk of patients assessed for LT. In this single center, observational study we included 54 consecutive patients who were assessed for LT and consequently transplanted. Twenty-four patients (44%) presented with a high CCS above 300 and/or a significant stenosis (>50% percent narrowing due to stenotic plaques) and were further referred to coronary angiography. Three of these patients had a more than 70% LAD stenosis with subsequent angioplasty (n=1) or conservative therapy (n=2). The other patients showed only diffuse CAD without significant stenosis. The remaining 30 patients with normal CTA findings were listed for LT without further tests. None of the 54 patients developed cardiovascular events peri- and postoperatively. This study indicated that CTA combined with CCS is a useful non-invasive imaging technique for pre-LT assessment of coronary artery disease and safe tool in the risk assessment of peri- and postoperative cardiovascular events in patients undergoing LT. PMID:21665396

  7. A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia.

    PubMed

    Moorman, Anthony V; Enshaei, Amir; Schwab, Claire; Wade, Rachel; Chilton, Lucy; Elliott, Alannah; Richardson, Stacey; Hancock, Jeremy; Kinsey, Sally E; Mitchell, Christopher D; Goulden, Nicholas; Vora, Ajay; Harrison, Christine J

    2014-08-28

    Recent genomic studies have provided a refined genetic map of acute lymphoblastic leukemia (ALL) and increased the number of potential prognostic markers. Therefore, we integrated copy-number alteration data from the 8 most commonly deleted genes, subordinately, with established chromosomal abnormalities to derive a 2-tier genetic classification. The classification was developed using 809 ALL97/99 patients and validated using 742 United Kingdom (UK)ALL2003 patients. Good-risk (GR) genetic features included ETV6-RUNX1, high hyperdiploidy, normal copy-number status for all 8 genes, isolated deletions affecting ETV6/PAX5/BTG1, and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. All other genetic features were classified as poor risk (PR). Three-quarters of UKALL2003 patients had a GR genetic profile and a significantly improved event-free survival (EFS) (94%) compared with patients with a PR genetic profile (79%). This difference was driven by a lower relapse rate (4% vs 17%), was seen across all patient subgroups, and was independent of other risk factors. Even genetic GR patients with minimal residual disease (>0.01%) at day 29 had an EFS in excess of 90%. In conclusion, the integration of genomic and cytogenetic data defines 2 subgroups with distinct responses to treatment and identifies a large subset of children suitable for treatment deintensification. PMID:24957142

  8. Comparison of nonlinear methods symbolic dynamics, detrended fluctuation, and Poincaré plot analysis in risk stratification in patients with dilated cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Voss, Andreas; Schroeder, Rico; Truebner, Sandra; Goernig, Matthias; Figulla, Hans Reiner; Schirdewan, Alexander

    2007-03-01

    Dilated cardiomyopathy (DCM) has an incidence of about 20/100 000 new cases per annum and accounts for nearly 10 000 deaths per year in the United States. Approximately 36% of patients with dilated cardiomyopathy (DCM) suffer from cardiac death within five years after diagnosis. Currently applied methods for an early risk prediction in DCM patients are rather insufficient. The objective of this study was to investigate the suitability of short-term nonlinear methods symbolic dynamics (STSD), detrended fluctuation (DFA), and Poincaré plot analysis (PPA) for risk stratification in these patients. From 91 DCM patients and 30 healthy subjects (REF), heart rate and blood pressure variability (HRV, BPV), STSD, DFA, and PPA were analyzed. Measures from BPV analysis, DFA, and PPA revealed highly significant differences (p<0.0011) discriminating REF and DCM. For risk stratification in DCM patients, four parameters from BPV analysis, STSD, and PPA revealed significant differences between low and high risk (maximum sensitivity: 90%, specificity: 90%). These results suggest that STSD and PPA are useful nonlinear methods for enhanced risk stratification in DCM patients.

  9. National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

    PubMed Central

    Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D; Eden, Svetlana K; Fihn, Stephan D; Nielson, Christopher D; Peterson, Josh F; Baker, Clifton R; Ikizler, T Alp; Speroff, Theodore

    2015-01-01

    Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention. Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance. Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission. Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant. PMID:26104740

  10. Incidence, risk stratification, antibiogram of pathogens isolated and clinical outcome of ventilator associated pneumonia

    PubMed Central

    Gupta, Alok; Agrawal, Avinash; Mehrotra, Sanjay; Singh, Abhishek; Malik, Shruti; Khanna, Arjun

    2011-01-01

    Background: The initial empirical therapy of Ventilator Associated Pneumonia (VAP) modified based on the knowledge of local microbiological data is associated with decreased morbidity and mortality. The objective was to find the incidence and risk factors associated with VAP, the implicated pathogens and their susceptibility pattern as well as to assess the final clinical outcome in VAP. Materials and Methods: This was a prospective cohort study of 107 patients taken on ventilatory support for two or more days and those not suffering from pneumonia prior were to be taken on ventilator. The study was done over a period of one year. VAP was diagnosed using clinical pulmonary infection score of >6. The mortality, incidence of VAP, frequency of different pathogens isolated, their antibiotic sensitivity pattern, duration of mechanical ventilation and duration of hospital stay were assessed. Statistical Analysis: Univariate analysis, χ2 test and paired t-test. Results: The incidence of VAP was 28.04%. Mortality in VAP group was 46.67%, while in the non-VAP group was 27.28%. High APACHE II score was associated with a high mortality rate as well as increased incidence of VAP. The most common organisms isolated from endotracheal aspirate of patients who developed VAP were Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Acinetobacter baumannii. Most strains of Pseudomonas (55.56%) were resistant to commonly used beta-lactam antibiotics known to be effective against Pseudomonas. All strains of Staphylococcus aureus were MRSA and most isolates of K. pneumoniae (85.71%) were extended-spectrum beta-lactamase producing. About 50% isolates of Acinetobacter were resistant to carbapenems. Mortality was highest for infections caused by A. baumannii (83.33%) and K. pneumoniae (71.42%). Conclusions: APACHE II score can be used to stratify the risk of development of VAP and overall risk of mortality. Drug-resistant strains of

  11. Can Ambulatory Blood Pressure Variability Contribute to Individual Cardiovascular Risk Stratification?

    PubMed

    Magdás, Annamária; Szilágyi, László; Incze, Alexandru

    2016-01-01

    Objective. The aim of this study is to define the normal range for average real variability (ARV) and to establish whether it can be considered as an additional cardiovascular risk factor. Methods. In this observational study, 110 treated hypertensive patients were included and admitted for antihypertensive treatment adjustment. Circadian blood pressure was recorded with validated devices. Blood pressure variability (BPV) was assessed according to the ARV definition. Based on their variability, patients were classified into low, medium, and high variability groups using the fuzzy c-means algorithm. To assess cardiovascular risk, blood samples were collected. Characteristics of the groups were compared by ANOVA tests. Results. Low variability was defined as ARV below 9.8 mmHg (32 patients), medium as 9.8-12.8 mmHg (48 patients), and high variability above 12.8 mmHg (30 patients). Mean systolic blood pressure was 131.2 ± 16.7, 135.0 ± 12.1, and 141.5 ± 11.4 mmHg in the low, medium, and high variability groups, respectively (p = 0.0113). Glomerular filtration rate was 78.6 ± 29.3, 74.8 ± 26.4, and 62.7 ± 23.2 mL/min/1.73 m(2) in the low, medium, and high variability groups, respectively (p = 0.0261). Conclusion. Increased values of average real variability represent an additional cardiovascular risk factor. Therefore, reducing BP variability might be as important as achieving optimal BP levels, but there is need for further studies to define a widely acceptable threshold value. PMID:27247614

  12. Can Ambulatory Blood Pressure Variability Contribute to Individual Cardiovascular Risk Stratification?

    PubMed Central

    Magdás, Annamária; Szilágyi, László; Incze, Alexandru

    2016-01-01

    Objective. The aim of this study is to define the normal range for average real variability (ARV) and to establish whether it can be considered as an additional cardiovascular risk factor. Methods. In this observational study, 110 treated hypertensive patients were included and admitted for antihypertensive treatment adjustment. Circadian blood pressure was recorded with validated devices. Blood pressure variability (BPV) was assessed according to the ARV definition. Based on their variability, patients were classified into low, medium, and high variability groups using the fuzzy c-means algorithm. To assess cardiovascular risk, blood samples were collected. Characteristics of the groups were compared by ANOVA tests. Results. Low variability was defined as ARV below 9.8 mmHg (32 patients), medium as 9.8–12.8 mmHg (48 patients), and high variability above 12.8 mmHg (30 patients). Mean systolic blood pressure was 131.2 ± 16.7, 135.0 ± 12.1, and 141.5 ± 11.4 mmHg in the low, medium, and high variability groups, respectively (p = 0.0113). Glomerular filtration rate was 78.6 ± 29.3, 74.8 ± 26.4, and 62.7 ± 23.2 mL/min/1.73 m2 in the low, medium, and high variability groups, respectively (p = 0.0261). Conclusion. Increased values of average real variability represent an additional cardiovascular risk factor. Therefore, reducing BP variability might be as important as achieving optimal BP levels, but there is need for further studies to define a widely acceptable threshold value. PMID:27247614

  13. Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management.

    PubMed

    Patnaik, Mrinal M; Tefferi, Ayalew

    2016-06-01

    Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 × 10(9) /L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼20-30% of patients, while >90% have gene mutations. Mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent; with only ASXL1 mutations negatively impacting overall survival. Two molecularly integrated, CMML-specific prognostic models include; the Groupe Français des Myélodysplasies (GFM) and the Molecular Mayo Model (MMM). The GFM model segregates patients into 3 groups based on: age >65 years, WBC >15 × 10(9) /L, anemia, platelets <100 × 10(9) /L, and ASXL1 mutation status, with respective median survivals of 56 (low), 27.4 (intermediate), and 9.2 (high) months. The MMM is based on ASXL1 mutational status, absolute monocyte count >10 × 10(9) /L, hemoglobin <10 g/dL, platelets <100 × 109/L and circulating immature myeloid cells. This model stratifies patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59, and 97 months, respectively. Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ∼30-40% and complete remission rates of ∼7-17%. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality. Individualized therapy, including epigenetic modifiers and small molecule inhibitors, are exciting prospects. Am. J. Hematol. 91:632-642, 2016. © 2016 Wiley Periodicals, Inc. PMID:27185207

  14. Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations.

    PubMed

    Bosse, Kristopher R; Maris, John M

    2016-01-01

    Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus and not only has catalyzed a more comprehensive understanding of neuroblastoma tumorigenesis but also has revealed novel oncogenic vulnerabilities that are being therapeutically leveraged. Neuroblastoma is a model pediatric solid tumor in its use of recurrent genomic alterations, such as high-level MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog) amplification, for risk stratification. Given the relative paucity of recurrent, activating, somatic point mutations or gene fusions in primary neuroblastoma tumors studied at initial diagnosis, innovative treatment approaches beyond small molecules targeting mutated or dysregulated kinases will be required moving forward to achieve noticeable improvements in overall patient survival. However, the clonally acquired, oncogenic aberrations in relapsed neuroblastomas are currently being defined and may offer an opportunity to improve patient outcomes with molecularly targeted therapy directed toward aberrantly regulated pathways in relapsed disease. This review summarizes the current state of knowledge about neuroblastoma genetics and genomics, highlighting the improved prognostication and potential therapeutic opportunities that have arisen from recent advances in understanding germline predisposition, recurrent segmental chromosomal alterations, somatic point mutations and translocations, and clonal evolution in relapsed neuroblastoma. PMID:26539795

  15. Atherosclerotic risk stratification strategy for carotid arteries using texture-based features.

    PubMed

    Acharya, U Rajendra; Sree, S Vinitha; Krishnan, M Muthu Rama; Molinari, Filippo; Saba, Luca; Ho, Sin Yee Stella; Ahuja, Anil T; Ho, Suzanne C; Nicolaides, Andrew; Suri, Jasjit S

    2012-06-01

    Plaques in the carotid artery result in stenosis, which is one of the main causes for stroke. Patients have to be carefully selected for stenosis treatments as they carry some risk. Since patients with symptomatic plaques have greater risk for strokes, an objective classification technique that classifies the plaques into symptomatic and asymptomatic classes is needed. We present a computer aided diagnostic (CAD) based ultrasound characterization methodology (a class of Atheromatic systems) that classifies the patient into symptomatic and asymptomatic classes using two kinds of datasets: (1) plaque regions in ultrasound carotids segmented semi-automatically and (2) far wall gray-scale intima-media thickness (IMT) regions along the common carotid artery segmented automatically. For both kinds of datasets, the protocol consists of estimating texture-based features in frameworks of local binary patterns (LBP) and Law's texture energy (LTE) and applying these features for obtaining the training parameters, which are then used for classification. Our database consists of 150 asymptomatic and 196 symptomatic plaque regions and 342 IMT wall regions. When using the Atheromatic-based system on semiautomatically determined plaque regions, support vector machine (SVM) classifier was adapted with highest accuracy of 83%. The accuracy registered was 89.5% on the far wall gray-scale IMT regions when using SVM, K-nearest neighbor (KNN) or radial basis probabilistic neural network (RBPNN) classifiers. LBP/LTE-based techniques on both kinds of carotid datasets are noninvasive, fast, objective and cost-effective for plaque characterization and, hence, will add more value to the existing carotid plaque diagnostics protocol. We have also proposed an index for each type of datasets: AtheromaticPi, for carotid plaque region, and AtheromaticWi, for IMT carotid wall region, based on the combination of the respective significant features. These indices show a separation between symptomatic

  16. Development of a Risk Stratification System to Guide Treatment for Female Germ Cell Tumors

    PubMed Central

    Meisel, Jane L.; Woo, Kaitlin M.; Sudarsan, Nora; Eng, Jana; Patil, Sujata; Jacobsen, Erin P.; Murali, Rajmohan; Gardner, Ginger J.; Bosl, George J.; Aghajanian, Carol; Feldman, Darren R.

    2016-01-01

    Objective Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer. Methods Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome. Results Of 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76-92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12). Conclusions Modified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT. PMID:26115974

  17. Artificial neural network modeling enhances risk stratification and can reduce downstream testing for patients with suspected acute coronary syndromes, negative cardiac biomarkers, and normal ECGs.

    PubMed

    Isma'eel, Hussain A; Cremer, Paul C; Khalaf, Shaden; Almedawar, Mohamad M; Elhajj, Imad H; Sakr, George E; Jaber, Wael A

    2016-04-01

    Despite uncertain yield, guidelines endorse routine stress myocardial perfusion imaging (MPI) for patients with suspected acute coronary syndromes, unremarkable serial electrocardiograms, and negative troponin measurements. In these patients, outcome prediction and risk stratification models could spare unnecessary testing. This study therefore investigated the use of artificial neural networks (ANN) to improve risk stratification and prediction of MPI and angiographic results. We retrospectively identified 5354 consecutive patients referred from the emergency department for rest-stress MPI after serial negative troponins and normal ECGs. Patients were risk stratified according to thrombolysis in myocardial infarction (TIMI) scores, ischemia was defined as >5 % reversible perfusion defect, and obstructive coronary artery disease was defined as >50 % angiographic obstruction. For ANN, the network architecture employed a systematic method where the number of neurons is changed incrementally, and bootstrapping was performed to evaluate the accuracy of the models. Compared to TIMI scores, ANN models provided improved discriminatory power. With regards to MPI, an ANN model could reduce testing by 59 % and maintain a 96 % negative predictive value (NPV) for ruling out ischemia. Application of an ANN model could also avoid 73 % of invasive coronary angiograms while maintaining a 98 % NPV for detecting obstructive CAD. An online calculator for clinical use was created using these models. The ANN models improved risk stratification when compared to the TIMI score. Our calculator could also reduce downstream testing while maintaining an excellent NPV, though further study is needed before the calculator can be used clinically. PMID:26626458

  18. TP53 Mutational Status Is a Potential Marker for Risk Stratification in Wilms Tumour with Diffuse Anaplasia

    PubMed Central

    Chagtai, Tasnim; Popov, Sergey D.; Sebire, Neil J.; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R.; Grundy, Paul; Dome, Jeffrey S.; Pritchard-Jones, Kathy

    2014-01-01

    Purpose The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. Patients and Methods We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. PMID:25313908

  19. New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome.

    PubMed

    Roma, Andres A; Mistretta, Toni-Ann; Diaz De Vivar, Andrea; Park, Kay J; Alvarado-Cabrero, Isabel; Rasty, Golnar; Chanona-Vilchis, Jose G; Mikami, Yoshiki; Hong, Sung R; Teramoto, Norihiro; Ali-Fehmi, Rouba; Barbuto, Denise; Rutgers, Joanne K L; Silva, Elvio G

    2016-04-01

    We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors. PMID:27016227

  20. Identifying Unique Versus Shared Pre- and Perinatal Risk Factors for ASD and ADHD Using a Simplex-Multiplex Stratification.

    PubMed

    Oerlemans, Anoek M; Burmanje, Marlot J; Franke, Barbara; Buitelaar, Jan K; Hartman, Catharina A; Rommelse, Nanda N J

    2016-07-01

    Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Besides shared genetic factors, pre- and perinatal risk factors (PPFs) may determine if ASD, ADHD, or the combination of both disorders becomes manifest. This study aimed to test shared and unique involvement of PPFs for ASD and ADHD, using an approach that stratifies the sample into affected/unaffected offspring and single-incidence (SPX) versus multi-incidence (MPX) families. Pre- perinatal data based on retrospective parent-report were collected in 288 children (71 % males) from 31 SPX and 59 MPX ASD families, 476 children (65 % males) from 31 SPX and 171 MPX ADHD families, and 408 control children (42 % males). Except for large family size and more firstborns amongst affected offspring, no shared PFFs were identified for ASD and ADHD. PPFs predominantly related to ASD (maternal infections and suboptimal condition at birth) were more often reported in affected than unaffected siblings. PPFs associated with ADHD (low parental age, maternal diseases, smoking and stress) were shared between affected and unaffected siblings. Firstborn-ship was more frequent in SPX than MPX ASD probands. Our results suggest that the co-morbidity of ASD and ADHD is not likely explained by shared PPFs. Instead, PPFs might play a crucial role in the developmental pathways leading up to either disorder. PPFs in ADHD appear to index an increased shared risk, whereas in ASD PPFs possibly have a more determining role in the disorder. SPX-MPX stratification detected possible etiological differences in ASD families, but provided no deeper insight in the role of PPFs in ADHD. PMID:26466830

  1. Dipyridamole thallium-201 scintigraphy for early risk stratification of patients after uncomplicated myocardial infarction

    PubMed Central

    Hung, J.; Moshiri, M.; Groom, G.; Van der Schaaf, A. A; Parsons, R.; Hands, M.

    1997-01-01

    Objective—To determine the safety and prognostic value of dipyridamole thallium-201 scintigraphy performed in patients within three to five days of acute myocardial infarction, including those receiving thrombolytic treatment.
Design—A prospective study of dipyridamole thallium-201 scintigraphy in patients early after acute myocardial infarction.
Setting—University hospital.
Patients—200 patients who were clinically uncomplicated at day 3 after infarction, 92 (46%) of whom had received thrombolysis.
Main outcome measures—Incidence of cardiac death, non-fatal reinfarction, readmission to hospital for unstable angina, or non-elective revascularisation procedure within six months' follow up. 
Results—No patient had a serious complication from the dipyridamole study. At six month follow up, 55 patients (28%) had suffered a defined cardiac event. Patients who received thrombolysis had the same extent of thallium-201 redistribution and the same occurrence of subsequent cardiac events as those not receiving thrombolysis. Patients who subsequently had an event had more myocardial segments showing thallium-201 redistribution than event free patients: 2.7 (SD 1.9) v 1.2 (1.4), respectively (p < 0.001). Among all clinical and scintigraphic variables, multivariate analysis identified the extent of thallium-201 redistribution as the only independent predictor of outcome (p < 0.001). Among 63 patients (32%) of the study cohort who showed more than two myocardial segments with thallium-201 redistribution, the adjusted risk ratio for a cardiac event was 7.5 (95% confidence interval 2.9 to 19.1) compared with patients without any redistribution.
Conclusions—Dipyridamole thallium-201 scintigraphy can be performed safely within a few days of the event in patients with uncomplicated myocardial infarction, including those who received thrombolysis, and can identify a subgroup of patients at high risk of future ischaemic events.

 Keywords

  2. Risk stratification for COPD diagnosis through an active search strategy in primary care

    PubMed Central

    Marcos, Pedro J; Malo de Molina, Rosa; Casamor, Ricard

    2016-01-01

    Background The aim of this study was to identify the percentage of undiagnosed patients with COPD through the implementation of an active search strategy in a selected subject population. Methods An observational, cross-sectional, multicenter study was conducted in a primary care setting in Spain. General practitioners gave their diagnostic impression of COPD (yes/no) on the basis of clinical criteria of subjects with respiratory symptoms and tobacco exposure. Subsequently, post-bronchodilator spirometry and quality-of-life tests were performed. Multivariate logistic regression techniques using receiver operating characteristic (ROC) curves were used to identify the combination of variables that best discriminates COPD. Results A total of 2,758 patients were screened at 368 primary care centers, of which 1,725 patients were included in the study. Seven hundred and ninety-three patients (46%) were diagnosed with COPD. Clinical judgment resulted in suspected COPD in 1,393 (81%) of the subjects. The best variables to discriminate COPD were a history of lower respiratory tract infections, cough, and dyspnea. This combination identified COPD with a ROCAUC of 0.61 denoting a poor discriminative ability. Conclusion Employing an active search strategy leads to a new COPD diagnosis in almost half of the subjects. Screening of COPD with post-bronchodilator spirometry should be considered mandatory for any high-risk subject visiting the general practitioner clinic for any reason. PMID:27042035

  3. Matrix metalloproteinases and risk stratification in patients undergoing surgical revascularisation for critical limb ischaemia.

    PubMed

    De Caridi, Giovanni; Massara, Mafalda; Spinelli, Francesco; David, Antonio; Gangemi, Sebastiano; Fugetto, Francesco; Grande, Raffaele; Butrico, Lucia; Stefanelli, Roberta; Colosimo, Manuela; de Franciscis, Stefano; Serra, Raffaele

    2016-08-01

    Critical limb ischaemia (CLI) is the most advanced form of peripheral artery disease (PAD) and it is often associated with foot gangrene, which may lead to major amputation of lower limbs, and also with a higher risk of death due to fatal cardiovascular events. Matrix metalloproteinases (MMPs) seem to be involved in atherosclerosis, PAD and CLI. Aim of this study was to evaluate variations in MMP serum levels in patients affected by CLI, before and after lower limb surgical revascularisation through prosthetic or venous bypass. A total of 29 patients (7 females and 22 males, mean age 73·4 years, range 65-83 years) suffering from CLI and submitted to lower extremity bypass (LEB) in our Institution were recruited. Seven patients (group I) underwent LEB using synthetic polytetrafluoroethylene (PTFE) graft material and 22 patients (group II) underwent LEB using autogenous veins. Moreover, 30 healthy age-sex-matched subjects were also enrolled as controls (group III). We documented significantly higher serum MMPs levels (P < 0·01) in patients with CLI (groups I and II) with respect to control group (group III). Finally, five patients with CLI (17·2%) showed poor outcomes (major amputations or death), and enzyme-linked immunosorbent assay (ELISA) test showed very high levels of MMP-1 and MMP-8. MMP serum levels seem to be able to predict the clinical outcomes of patients with CLI. PMID:26012891

  4. Incorporating temporal EHR data in predictive models for risk stratification of renal function deterioration.

    PubMed

    Singh, Anima; Nadkarni, Girish; Gottesman, Omri; Ellis, Stephen B; Bottinger, Erwin P; Guttag, John V

    2015-02-01

    Predictive models built using temporal data in electronic health records (EHRs) can potentially play a major role in improving management of chronic diseases. However, these data present a multitude of technical challenges, including irregular sampling of data and varying length of available patient history. In this paper, we describe and evaluate three different approaches that use machine learning to build predictive models using temporal EHR data of a patient. The first approach is a commonly used non-temporal approach that aggregates values of the predictors in the patient's medical history. The other two approaches exploit the temporal dynamics of the data. The two temporal approaches vary in how they model temporal information and handle missing data. Using data from the EHR of Mount Sinai Medical Center, we learned and evaluated the models in the context of predicting loss of estimated glomerular filtration rate (eGFR), the most common assessment of kidney function. Our results show that incorporating temporal information in patient's medical history can lead to better prediction of loss of kidney function. They also demonstrate that exactly how this information is incorporated is important. In particular, our results demonstrate that the relative importance of different predictors varies over time, and that using multi-task learning to account for this is an appropriate way to robustly capture the temporal dynamics in EHR data. Using a case study, we also demonstrate how the multi-task learning based model can yield predictive models with better performance for identifying patients at high risk of short-term loss of kidney function. PMID:25460205

  5. Incorporating temporal EHR data in predictive models for risk stratification of renal function deterioration

    PubMed Central

    Singh, Anima; Nadkarni, Girish; Gottesman, Omri; Ellis, Stephen B.; Bottinger, Erwin P.; Guttag, John V.

    2015-01-01

    Predictive models built using temporal data in electronic health records (EHRs) can potentially play a major role in improving management of chronic diseases. However, these data present a multitude of technical challenges, including irregular sampling of data and varying length of available patient history. In this paper, we describe and evaluate three different approaches that use machine learning to build predictive models using temporal EHR data of a patient. The first approach is a commonly used non-temporal approach that aggregates values of the predictors in the patient’s medical history. The other two approaches exploit the temporal dynamics of the data. The two temporal approaches vary in how they model temporal information and handle missing data. Using data from the EHR of Mount Sinai Medical Center, we learned and evaluated the models in the context of predicting loss of estimated glomerular filtration rate (eGFR), the most common assessment of kidney function. Our results show that incorporating temporal information in patient’s medical history can lead to better prediction of loss of kidney function. They also demonstrate that exactly how this information is incorporated is important. In particular, our results demonstrate that the relative importance of different predictors varies over time, and that using multi-task learning to account for this is an appropriate way to robustly capture the temporal dynamics in EHR data. Using a case study, we also demonstrate how the multi-task learning based model can yield predictive models with better performance for identifying patients at high risk of short-term loss of kidney function. PMID:25460205

  6. Risk stratification for the recurrence of trigger thumb after surgical release in the paediatric patient.

    PubMed

    Edwards, D S; Richards, R H

    2016-08-01

    Trigger thumb, or stenosing tenovaginitis, is a relatively uncommon condition affecting the flexor pollicis longus tendon of children. The condition is characterized by the formation of a nodule within the tendon and thickening of the tendon sheath as it passes through the flexor pulley of the thumb at the level of the metacarpo-phalangeal joint. The optimum age for surgical intervention continues to be discussed. The aim of this study is to establish the temporal relationship and surgical variables to determine factors that may contribute to recurrence of the condition. A retrospective analysis of the entire surgical logbook and patient notes of a stand-alone consultant paediatric orthopaedic practice was scrutinized. 94 patients, 107 thumbs, over a 13-year period were operated on for trigger thumb. The recurrence rate was found to be 5.61 %. The average age of patients at primary release who went on to recurrence was 2.8 years, which is significantly younger than those that did not recur (p = 0.044). Sensitivity analysis revealed that the primary procedure at an age of less than 2.5 years confers a higher risk of recurrence. The data presented here advocate surgical release of trigger thumb after 2½ years of age, a senior surgeon as lead operator and a transverse skin incision at the level of the nodule or a more extensive "zig-zag" one to clearly see the structures to be released. We recommend that the surgeon ensures the stenosing pulley and sheath are released in their entirety. PMID:27352865

  7. Predictive risk stratification model: a progressive cluster-randomised trial in chronic conditions management (PRISMATIC) research protocol

    PubMed Central

    2013-01-01

    Background An ageing population increases demand on health and social care. New approaches are needed to shift care from hospital to community and general practice. A predictive risk stratification tool (Prism) has been developed for general practice that estimates risk of an emergency hospital admission in the following year. We present a protocol for the evaluation of Prism. Methods/Design We will undertake a mixed methods progressive cluster-randomised trial. Practices begin as controls, delivering usual care without Prism. Practices will receive Prism and training randomly, and thereafter be able to use Prism with clinical and technical support. We will compare costs, processes of care, satisfaction and patient outcomes at baseline, 6 and 18 months, using routine data and postal questionnaires. We will assess technical performance by comparing predicted against actual emergency admissions. Focus groups and interviews will be undertaken to understand how Prism is perceived and adopted by practitioners and policy makers. We will model data using generalised linear models and survival analysis techniques to determine whether any differences exist between intervention and control groups. We will take account of covariates and explanatory factors. In the economic evaluation we will carry out a cost-effectiveness analysis to examine incremental cost per emergency admission to hospital avoided and will examine costs versus changes in primary and secondary outcomes in a cost-consequence analysis. We will also examine changes in quality of life of patients across the risk spectrum. We will record and transcribe focus groups and interviews and analyse them thematically. We have received full ethical and R&D approvals for the study and Information Governance Review Panel (IGRP) permission for the use of routine data. We will comply with the CONSORT guidelines and will disseminate the findings at national and international conferences and in peer-reviewed journals

  8. Risk Stratification of Patients with Peripheral Arterial Disease and Abdominal Aortic Aneurysm Using Aortic Augmentation Index

    PubMed Central

    Beckmann, Marianne; Husmann, Marc

    2015-01-01

    Background Central augmentation index (cAIx) is an indicator for vascular stiffness. Obstructive and aneurysmatic vascular disease can affect pulse wave propagation and reflection, causing changes in central aortic pressures. Aim To assess and compare cAIx in patients with peripheral arterial disease (PAD) and / or abdominal aortic aneurysm (AAA). Methods cAIx was assessed by radial applanation tonometry (Sphygmocor) in a total of 184 patients at a tertiary referral centre. Patients were grouped as having PAD only, AAA only, or both AAA and PAD. Differences in cAIx measurements between the three patient groups were tested by non-parametric tests and stepwise multivariate linear regression analysis to investigate associations with obstructive or aneurysmatic patterns of vascular disease. Results In the study sample of 184 patients, 130 had PAD only, 20 had AAA only, and 34 patients had both AAA and PAD. Mean cAIx (%) was 30.5 ± 8.2 across all patients. It was significantly higher in females (35.2 ± 6.1, n = 55) than males (28.4 ± 8.2, n = 129), and significantly higher in patients over 80 years of age (34.4 ± 6.9, n = 22) than in those under 80 years (30.0 ± 8.2, n = 162). Intergroup comparison revealed a significant difference in cAIx between the three patient groups (AAA: 27.3 ± 9.5; PAD: 31.4 ± 7.8; AAA & PAD: 28.8 ± 8.5). cAIx was significantly lower in patients with AAA, higher in patients with both AAA and PAD, and highest in patients with PAD only (beta = 0.21, p = 0.006). Conclusion Non-invasive assessment of arterial stiffness in high-risk patients indicates that cAIx differs according to the pattern of vascular disease. Measurements revealed significantly higher cAIx values for patients with obstructive peripheral arterial disease than for patients with aneurysmatic disease. PMID:26452151

  9. Pharmacogenetic Risk Stratification in Angiotensin-Converting Enzyme Inhibitor-Treated Patients with Congestive Heart Failure: A Retrospective Cohort Study

    PubMed Central

    Nelveg-Kristensen, Karl Emil; Busk Madsen, Majbritt; Torp-Pedersen, Christian; Køber, Lars; Egfjord, Martin; Berg Rasmussen, Henrik; Riis Hansen, Peter

    2015-01-01

    Background Evidence for pharmacogenetic risk stratification of angiotensin-converting enzyme inhibitor (ACEI) treatment is limited. Therefore, in a cohort of ACEI-treated patients with congestive heart failure (CHF), we investigated the predictive value of two pharmacogenetic scores that previously were found to predict ACEI efficacy in patients with ischemic heart disease and hypertension, respectively. Score A combined single nucleotide polymorphisms (SNPs) of the angiotensin II receptor type 1 gene (rs275651 and rs5182) and the bradykinin receptor B1 gene (rs12050217). Score B combined SNPs of the angiotensin-converting enzyme gene (rs4343) and ABO blood group genes (rs495828 and rs8176746). Methods Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses. Results We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486) and all-cause death (P = 0.515 and P = 0.486) were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79–1.34] and HR 1.11 [95% CI 0.88–1.42]), score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59–1.08] and HR 0.91 [95% CI 0.70–1.20]), score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78–1.32] and HR 0.98 [95% CI 0.77–1.24]), and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75–1.41] and HR 1.05 [95% CI 0.79–1.40]), respectively. Conclusions We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI

  10. Development of a Risk Stratification Model for Delayed Inpatient Recovery of Physical Activities in Patients Undergoing Total Hip Replacement.

    PubMed

    Elings, Jordi; van der Sluis, Geert; Goldbohm, R Alexandra; Galindo Garre, Francisca; de Gast, Arthur; Hoogeboom, Thomas; van Meeteren, Nico L U

    2016-03-01

    Study Design Prospective cohort design using data derived from usual care. Background It is important that patients are able to function independently as soon as possible after total hip replacement. However, the speed of regaining activities differs significantly. Objectives To develop a risk stratification model (RSM) to predict delayed inpatient recovery of physical activities in people who underwent total hip replacement surgery. Methods This study was performed in 2 routine orthopaedic settings: Diakonessenhuis Hospital (setting A) and Nij Smellinghe Hospital (setting B). Preoperative screening was performed for all consecutive patients. In-hospital recovery of activities was assessed with the Modified Iowa Level of Assistance Scale. Delayed inpatient recovery of activities was defined as greater than 5 days. The RSM, developed using logistic regression analysis and bootstrapping, was based on data from setting A (n = 154). External validation was performed on the data set from setting B (n = 271). Results Twenty-one percent of the patients in setting A had a delayed recovery of activities during their hospital stay. Multivariable logistic regression modeling yielded a preliminary RSM that included the following factors: male sex (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.2, 2.6), 70 or more years of age (OR = 1.2; 95% CI: 0.4, 3.4), body mass index of 25 kg/m(2) or greater (OR = 2.2; 95% CI: 0.7, 7.4), an American Society of Anesthesiologists score of 3 (OR = 1.2; 95% CI: 0.3, 4.4), a Charnley score of B or C (OR = 6.1; 95% CI: 2.2, 17.4), and a timed up-and-go score of 12.5 seconds or greater (OR = 3.1; 95% CI: 1.1, 9.0). The area under the receiver operating characteristic (ROC) curve was 0.82 (95% CI: 0.74, 0.90) and the Hosmer-Lemeshow test score was 3.57 (P>.05). External validation yielded an area under the ROC curve of 0.71 (95% CI: 0.61, 0.81). Conclusion We demonstrated that the risk for delayed recovery of activities during the hospital

  11. Risk stratification in unstable angina and non-Q wave myocardial infarction using soluble cell adhesion molecules

    PubMed Central

    Mulvihill, N; Foley, J; Murphy, R; Curtin, R; Crean, P; Walsh, M

    2001-01-01

    are predictive of an increased risk of major adverse cardiovascular events six months after presentation with unstable angina and non-Q wave myocardial infarction. These findings suggest that the intensity of the vascular inflammatory process at the time of presentation is a determinant of clinical outcome in unstable coronary artery disease. 


Keywords: cell adhesion molecules; risk stratification; unstable angina PMID:11359739

  12. Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides

    PubMed Central

    Zeidan, AM; Sekeres, MA; Garcia-Manero, G; Steensma, DP; Zell, K; Barnard, J; Ali, NA; Zimmerman, C; Roboz, G; DeZern, A; Nazha, A; Jabbour, E; Kantarjian, H; Gore, SD; Maciejewski, JP; List, A; Komrokji, R

    2016-01-01

    Established prognostic tools in patients with myelodysplastic syndromes (MDS) were largely derived from untreated patient cohorts. Although azanucleosides are standard therapies for higher-risk (HR)-MDS, the relative prognostic performance of existing prognostic tools among patients with HR-MDS receiving azanucleoside therapy is unknown. In the MDS Clinical Research Consortium database, we compared the prognostic utility of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Prognostic Scoring System (MDAPSS), World Health Organization-based Prognostic Scoring System (WPSS) and the French Prognostic Scoring System (FPSS) among 632 patients who presented with HR-MDS and were treated with azanucleosides as the first-line therapy. Median follow-up from diagnosis was 15.7 months. No prognostic tool predicted the probability of achieving an objective response. Nonetheless, all five tools were associated with overall survival (OS, P = 0.025 for the IPSS, P = 0.011 for WPSS and P < 0.001 for the other three tools). The corrected Akaike Information Criteria, which were used to compare OS with the different prognostic scoring systems as covariates (lower is better) were 4138 (MDAPSS), 4156 (FPSS), 4196 (IPSS-R), 4186 (WPSS) and 4196 (IPSS). Patients in the highest-risk groups of the prognostic tools had a median OS from diagnosis of 11 – 16 months and should be considered for up-front transplantation or experimental approaches. PMID:26464171

  13. Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives

    PubMed Central

    Huebner, Thomas; Goernig, Matthias; Schuepbach, Michael; Sanz, Ernst; Pilgram, Roland; Seeck, Andrea; Voss, Andreas

    2010-01-01

    Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. Objectives: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD) and myocardial ischemia; secondarily, to explore the future perspectives of these methods. Methods: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. Results: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM); methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions. Telemedicine and ambient

  14. Clinical impact and risk stratification of balloon angioplasty for femoropopliteal disease in nitinol stenting era: Retrospective multicenter study using propensity score matching analysis

    PubMed Central

    Tsuchiya, Taketsugu; Takamura, Takaaki; Soga, Yoshimitsu; Iida, Osamu; Hirano, Keisuke; Suzuki, Kenji; Yamaoka, Terutoshi; Miyashita, Yusuke; Kitayama, Michihiko; Kajinami, Koji

    2016-01-01

    Objective: Nitinol stenting could bring the better outcome in endovascular therapy for femoropopliteal disease. However, it might be expected that recent marked advances in both device technology and operator technique had led to improved efficacy of balloon angioplasty even in this segment. The aims of this study were to evaluate the clinical impact of balloon angioplasty for femoropopliteal disease and make risk stratification clear by propensity score matching analysis. Methods: Based on the multicenter retrospective data, 2758 patients (balloon angioplasty: 729 patients and nitinol stenting: 2029 patients), those who underwent endovascular therapy for femoropopliteal disease, were analyzed. Results: The propensity score matching procedure extracted a total of 572 cases per group, and the primary patency rate of balloon angioplasty and nitinol stenting groups after matching was significantly the same (77.2% vs 82.7% at 1 year; 62.2% vs 64.3% at 3 years; 47.8% vs 54.3% at 5 years). In multivariate Cox hazard regression analysis, significant predictors for primary patency were diabetes mellitus, regular dialysis, cilostazol use, chronic total occlusion, and intra-vascular ultra-sonography use. The strategy of balloon angioplasty was not evaluated as a significant predictor for the primary patency. After risk stratification using five items (diabetes mellitus, regular dialysis, no use of intra-vascular ultra-sonography, chronic total occlusion, and no use of cilostazol: the DDICC score), the estimated primary patency rates of each group (low, DDICC score 0–2; moderate, DDICC score 3; high risk, DDICC score 4–5) were 88.6%, 78.3%, and 63.5% at 1 year; 75.2%, 60.7%, and 39.8% at 3 years; and 66.0%, 47.1%, and 26.3% at 5 years (p < 0.0001). The primary patency rate of balloon angioplasty and nitinol stenting groups was significantly the same in each risk stratification. Conclusion: This study suggests that balloon angioplasty does not have

  15. Outcomes of DES in Diabetic and Nondiabetic Patients with Complex Coronary Artery Disease after Risk Stratification by the SYNTAX Score

    PubMed Central

    Loutfi, Mohamed; Sadaka, Mohamed A.; Sobhy, Mohamed

    2016-01-01

    Diabetes mellitus (DM) increases the risk of adverse outcomes after coronary revascularization. Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). AIM The aim of this study was to assess the outcomes of drug-eluting stent (DES) insertion in DM and non-DM patients with complex coronary artery disease (CAD) after risk stratification by the percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score. METHODS AND RESULTS We performed multivessel percutaneous coronary intervention (PCI) for 601 lesions in 243 DM patients and 1,029 lesions in 401 non-DM patients. All included patients had MVD and one or more lesions of type B2/C. The two-year outcomes and event rates were estimated in the DM and non-DM patients using Kaplan–Meier analyses. The baseline SYNTAX score was ≤22 in 84.8% vs. 84%, P = 0.804, and 23–32 in 15.2% vs. 16%, P = 0.804, of the DM and non-DM patients, respectively. The number of diseased segments treated (2.57 ± 0.75 vs. 2.47 ± 0.72; P = 0.066) and stents implanted per patient (2.41 ± 0.63 vs. 2.32 ± 0.54; P = 0.134) were similar in both groups. After a mean follow-up of 642 ± 175 days, there were no differences in the major adverse cardiac and cerebrovascular events (MACCE; 26.7% vs. 20.9%; P = 0.091), composite end point of all-cause death/myocardial infarction (MI)/stroke (12.3% vs. 9%; P = 0.172), individual MACCE components of death (3.7% vs. 3.2%; P = 0.754), MI (6.6% vs. 4%; P = 0.142), and absence of stroke in the DM and non-DM patients. An increased need for repeat revascularization was observed in DM patients (18.5% vs. 10.2%; P = 0.003). In the multivariate analysis, DM was an independent predictor of repeat revascularization (hazard ratio: 1.818; 95% confidence interval: 1.162–2.843; P = 0.009). CONCLUSIONS DES implantation provides favorable early and mid-term results in both DM and non-DM patients undergoing PCI for

  16. Tree-structured Risk Stratification of In-hospital Mortality Following Percutaneous Coronary Intervention for Acute Myocardial Infarction: A Report From the New York State Percutaneous Coronary Intervention Database

    PubMed Central

    Negassa, Abdissa; Monrad, E. Scott; Bang, Ji Yon; Srinivas, V.S.

    2008-01-01

    BACKGROUND: Previous risk scores have shown excellent performance. However, the need for real-time risk score computation makes their implementation in an emergent situation challenging. A more simplified approach can provide practitioners with a practical bedside risk stratification tool. METHODS: We developed an easy-to-use tree-structured risk stratification model for patients undergoing early Percutaneous Coronary Intervention (PCI) for Acute Myocardial Infraction (AMI). The model was developed on the New York State PCI database for 1999-2000 (consisting of 5385 procedures) and was validated using the subsequent 2001-2002 database (consisting of 7414 procedures). RESULTS: Tree-structured modeling identified three key presenting features: cardiogenic shock, congestive heart failure and age. In the validation dataset, this risk stratification model identified patient groups with in-hospital mortality ranging from 0.5% to 20.6%, more than a twenty-fold increased risk. The performance of this model was similar to the Mayo Clinic Risk Score with a discriminative capacity of 82% (95% CI: 79%, 84%) versus 80% (95% CI: 77%, 82%), respectively. CONCLUSION: Patients undergoing PCI for AMI can be readily stratified into risk categories using the tree-structured model. This provides practicing cardiologists with an internally validated and easy-to-use scheme for in-hospital mortality risk stratification. PMID:17643583

  17. BAYESIAN BICLUSTERING FOR PATIENT STRATIFICATION.

    PubMed

    Khakabimamaghani, Sahand; Ester, Martin

    2016-01-01

    The move from Empirical Medicine towards Personalized Medicine has attracted attention to Stratified Medicine (SM). Some methods are provided in the literature for patient stratification, which is the central task of SM, however, there are still significant open issues. First, it is still unclear if integrating different datatypes will help in detecting disease subtypes more accurately, and, if not, which datatype(s) are most useful for this task. Second, it is not clear how we can compare different methods of patient stratification. Third, as most of the proposed stratification methods are deterministic, there is a need for investigating the potential benefits of applying probabilistic methods. To address these issues, we introduce a novel integrative Bayesian biclustering method, called B2PS, for patient stratification and propose methods for evaluating the results. Our experimental results demonstrate the superiority of B2PS over a popular state-of-the-art method and the benefits of Bayesian approaches. Our results agree with the intuition that transcriptomic data forms a better basis for patient stratification than genomic data. PMID:26776199

  18. Early Dynamic Risk Stratification with Baseline Troponin Levels and 90-minute ST Segment Resolution to Predict 30 Day Cardiovascular Mortality in STEMI: Analysis from CLARITY TIMI-28

    PubMed Central

    Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Jiang, Songtao; Bode, Christoph; Rifai, Nader; Gerszten, Robert E.; Gibson, C. Michael; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.

    2010-01-01

    Background Troponin is the preferred biomarker for risk stratification in non-ST-elevation ACS. The incremental prognostic utility of the initial magnitude of troponin elevation and its value in conjunction with ST segment resolution (STRes) in STEMI is less well-defined. Methods Troponin T (TnT) was measured in 1250 patients at presentation undergoing fibrinolysis for STEMI in CLARITY-TIMI 28. STRes was measured at 90 minutes. Multivariable logistic regression was used to examine the independent association between TnT levels, STRes, and 30-day cardiovascular (CV) mortality. Results Patients were classified into undetectable TnT at baseline (n=594), detectable but below the median of 0.12 ng/ml (n=330), and above the median (n=326). Rates of 30-day CV death were 1.5%, 4.5%, and 9.5% respectively (P<0.0001). Compared with those with undetectable levels and adjusting for baseline factors, the odds ratios for 30-day CV death were 4.56 (1.72-12.08, P=0.002) and 5.81 (2.29-14.73, P=0.0002) for those below and above the median, respectively. When combined with STRes, there was a significant gradient of risk, and in a multivariable model both baseline TnT (P=0.004) and STRes (P=0.003) were significant predictors of 30-day CV death. The addition of TnT and STRes to clinical risk factors significantly improved the C-statistic (0.86 to 0.90, P=0.02) and the integrated discriminative improvement 7.1% (P=0.0009). Conclusions Baseline TnT and 90-minute STRes are independent predictors of 30-day CV death in patients with STEMI. Use of these two simple, readily available tools can aid clinicians in early risk stratification. PMID:20569707

  19. Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score

    PubMed Central

    Tapper, Elliot B.; Hunink, M. G. Myriam; Afdhal, Nezam H.; Lai, Michelle; Sengupta, Neil

    2016-01-01

    Background The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists. Methods We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis. Results Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification. Conclusion Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice. PMID:26905872

  20. A New Bayesian Network-Based Risk Stratification Model for Prediction of Short-term and Long-term LVAD Mortality

    PubMed Central

    Loghmanpour, Natasha A.; Kanwar, Manreet K.; Druzdzel, Marek J.; Benza, Raymond L.; Murali, Srinivas; Antaki, James F.

    2015-01-01

    Existing risk assessment tools for patient selection for left ventricular assist devices (LVADs) such as the Destination Therapy Risk Score (DTRS) and HeartMate II Risk Score (HMRS) have limited predictive ability. This study aims to overcome the limitations of traditional statistical methods by performing the first application of Bayesian analysis to the comprehensive INTERMACS dataset and comparing it to HMRS. We retrospectively analyzed 8,050 continuous flow (CF) LVAD patients and 226 pre-implant variables. We then derived Bayesian models for mortality at each of five time endpoints post-implant (30 day, 90 day, 6 month, 1 year, and 2 year), achieving accuracies of 95, 90, 90, 83, and 78%, Kappa values of 0.43, 0.37, 0.37, 0.45, and 0.43, and area under the ROC of 91, 82, 82, 80 and 81% respectively. This was in comparison to the HMRS with an ROC of 57 and 60% at 90-days and 1-year, respectively. Pre-implant interventions such as dialysis, ECMO, and ventilators were major contributing risk markers. Bayesian models have the ability to reliably represent the complex causal relationships of multiple variables on clinical outcomes. Their potential to develop a reliable risk stratification tool for use in clinical decision making on LVAD patients encourages further investigation. PMID:25710772

  1. How accurately does the public perceive differences in transport risks? An exploratory analysis of scales representing perceived risk.

    PubMed

    Elvik, Rune; Bjørnskau, Torkel

    2005-11-01

    This paper probes the extent to which the public accurately perceives differences in transport risks. The paper is based on a survey of a random sample of the Norwegian population, conducted in September 2003. In the survey, respondents were asked: "How safe do you think it is to travel by means of (bus, train, etc.)?" Answers were given as: very safe, safe, a little unsafe, and very unsafe. A cursory examination of the answers suggested that the Norwegian public was quite well informed about differences in the risk of accident between different modes of transport, as well as between groups formed according to age and gender for each mode of transport. This paper probes the relationship between statistical estimates of risk and summary representations of perceived risk more systematically. It is found that the differences in fatality rate between different modes of transport are quite well perceived by the Norwegian public, irrespective of the way in which perceived risk is represented numerically. The relationship between statistical estimates of risk and numerical representations of perceived risk for each mode of transport is more sensitive to the choice of a numerical representation of perceived risk. A scale in which the answer "very safe" is assigned the value of 0.01 and the answer "very unsafe" is assigned the value of 10 is found to perform quite well. When the perception of risk is represented numerically according to this scale, a positive correlation between statistically estimated risk and perceived risk is found in seven of the eight comparisons that were made to determine how well variation in accident rates according to age and gender for car occupants, car drivers, cyclists and pedestrians are perceived. PMID:16054102

  2. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI).

    PubMed

    Mills, Joseph L; Conte, Michael S; Armstrong, David G; Pomposelli, Frank B; Schanzer, Andres; Sidawy, Anton N; Andros, George

    2014-01-01

    Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population. PMID:24126108

  3. Integrated e-Health approach based on vascular ultrasound and pulse wave analysis for asymptomatic atherosclerosis detection and cardiovascular risk stratification in the community.

    PubMed

    Santana, Daniel Bia; Zócalo, Yanina A; Armentano, Ricardo L

    2012-03-01

    New strategies are urgently needed to identify subjects at increased risk of atherosclerotic cardiovascular disease (ACVD) development or complications. A National Public University Center (CUiiDARTE) was created in Uruguay, based on six main pillars: 1) integration of experts in different disciplines and creation of multidisciplinary teams, 2) incidence in public and professional education programs to give training in the use of new technologies and to shift the focus from ACVD treatment to disease prevention, 3) implementation of free vascular studies in the community (distributed rather than centralized healthcare), 4) innovation and application of e-Health and noninvasive technology and approaches, 5) design and development of a biomedical approach to determine the target population and patient workflow, and 6) improvement in individual risk estimation and differentiation between aging and ACVD-related arterial changes using population-based epidemiological and statistical patient-specific models. This work describes main features of CUiiDARTE project implementation, the scientific and technological steps and innovations done for individual risk stratification, and sub-clinical ACVD diagnosis. PMID:22271835

  4. Body Mass Index as a Predictor of Sudden Cardiac Death and Usefulness of the Electrocardiogram for Risk Stratification.

    PubMed

    Eranti, Antti; Aro, Aapo L; Kerola, Tuomas; Tikkanen, Jani T; Rissanen, Harri A; Anttonen, Olli; Junttila, M Juhani; Knekt, Paul; Huikuri, Heikki V

    2016-02-01

    Evidence of the role of body mass index (BMI) as a risk factor for sudden cardiac death (SCD) is conflicting, and how electrocardiographic (ECG) SCD risk markers perform in subjects with different BMIs is not known. In this study, a general population cohort consisting of 10,543 middle-aged subjects (mean age 44 years, 52.7% men) was divided into groups of lean (BMI <20, n = 374), normal weight (BMI 20.0 to 24.9, n = 4,334), overweight (BMI 25.0 to 29.9, n = 4,390), and obese (BMI >30, n = 1,445) subjects. Cox proportional hazards models adjusted for confounders were used to assess the risk for SCD associated with BMI and the risk for SCD associated with ECG abnormalities in subjects with different BMIs. The overweight and obese subjects were at increased risk for SCD (hazard ratios [95% CIs] were 1.33 [1.13 to 1.56], p = 0.001 and 1.79 [1.44 to 2.23], p <0.001 for overweight and obese subjects, respectively). The risk of non-SCD had a similar relation with BMI as SCD. Hazard ratios associated with ECG abnormalities were 3.03, 1.75, 1.74, and 1.34 in groups of lean, normal weight, overweight, and obese subjects, respectively, but no statistical significance was reached in the obese. ECG abnormalities improved integrated discrimination indexes and continuous net reclassification indexes statistically significantly only in the normal weight group. In conclusion, the overweight and obese are at increased risk for SCD but also for non-SCD, and ECG abnormalities are associated with increased risk of SCD also in normal weight subjects presenting with less traditional cardiovascular risk factors. PMID:26723105

  5. Malaria ecotypes and stratification.

    PubMed

    Schapira, Allan; Boutsika, Konstantina

    2012-01-01

    To deal with the variability of malaria, control programmes need to stratify their malaria problem into a number of smaller units. Such stratification may be based on the epidemiology of malaria or on its determinants such as ecology. An ecotype classification was developed by the World Health Organization (WHO) around 1990, and it is time to assess its usefulness for current malaria control as well as for malaria modelling on the basis of published research. Journal and grey literature was searched for articles on malaria or Anopheles combined with ecology or stratification. It was found that all malaria in the world today could be assigned to one or more of the following ecotypes: savanna, plains and valleys; forest and forest fringe; foothill; mountain fringe and northern and southern fringes; desert fringe; coastal and urban. However, some areas are in transitional or mixed zones; furthermore, the implications of any ecotype depend on the biogeographical region, sometimes subregion, and finally, the knowledge on physiography needs to be supplemented by local information on natural, anthropic and health system processes including malaria control. Ecotyping can therefore not be seen as a shortcut to determine control interventions, but rather as a framework to supplement available epidemiological and entomological data so as to assess malaria situations at the local level, think through the particular risks and opportunities and reinforce intersectoral action. With these caveats, it does however emerge that several ecotypic distinctions are well defined and have relatively constant implications for control within certain biogeographic regions. Forest environments in the Indo-malay and the Neotropics are, with a few exceptions, associated with much higher malaria risk than in adjacent areas; the vectors are difficult to control, and the anthropic factors also often converge to impose constraints. Urban malaria in Africa is associated with lower risk than savanna

  6. Combined model of the EBMT score modified model and the HCT-CI improves the stratification of high-risk patients undergoing unmanipulated haploidentical blood and marrow transplantation.

    PubMed

    Chang, Ying-Jun; Wang, Hong-Tao; Xu, Lan-Ping; Wang, Yu; Liu, Kai-Yan; Zhang, Xiao-Hui; Liu, Dai-Hong; Chen, Huan; Chen, Yu-Hong; Wang, Feng-Rong; Han, Wei-; Sun, Yu-Qian; Yan, Chen-Hua; Tang, Fei-Fei; Mo, Xiao-Dong; Huang, Xiao-Jun

    2016-09-01

    Both European Group for blood and marrow transplantation risk score (EBMT score modified model) and hematopoietic cell transplantation comorbidity index (HCT-CI) are suitable for evaluating patients undergoing unmanipulated haploidentical blood and marrow transplantation (HBMT), while the predictive capacity of the combined model following haploidentical transplantation is still unknown. In this study, we calculated and validated 322 consecutive unmanipulated HBMT patients. Patients in groups with HCT-CI scores of 0 or 1-2 exhibited similar overall survival (OS), non-relapse mortality (NRM), and relapse rates, independent of their EBMT score modified model. In the group in which patients' HCT-CI scores were ≥3, patients with high EBMT score modified model showed lower OS (p = 0.003) and higher NRM (p = 0.001) than did patients with low EBMT score. In conclusion, this combined model can be used to predict outcomes and may improve the stratification of high-risk patients following unmanipulated HBMT. PMID:26857549

  7. Recent advances in the management of chronic stable angina I: Approach to the patient, diagnosis, pathophysiology, risk stratification, and gender disparities

    PubMed Central

    Kones, Richard

    2010-01-01

    The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the

  8. A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

    SciTech Connect

    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common

  9. Reflex and Tonic Autonomic Markers for Risk Stratification in Patients With Type 2 Diabetes Surviving Acute Myocardial Infarction

    PubMed Central

    Barthel, Petra; Bauer, Axel; Müller, Alexander; Junk, Nadine; Huster, Katharina M.; Ulm, Kurt; Malik, Marek; Schmidt, Georg

    2011-01-01

    OBJECTIVE Diabetic postinfarction patients are at increased mortality risk compared with nondiabetic postinfarction patients. In a substantial number of these patients, diabetic cardiac neuropathy already preexists at the time of the infarction. In the current study we investigated if markers of autonomic dysfunction can further discriminate diabetic postinfarction patients into low- and high-risk groups. RESEARCH DESIGN AND METHODS We prospectively enrolled 481 patients with type 2 diabetes who survived acute myocardial infarction (MI), were aged ≤80 years, and presented in sinus rhythm. Primary end point was total mortality at 5 years of follow-up. Severe autonomic failure (SAF) was defined as coincidence of abnormal autonomic reflex function (assessed by means of heart rate turbulence) and of abnormal autonomic tonic activity (assessed by means of deceleration capacity of heart rate). Multivariable risk analyses considered SAF and standard risk predictors including history of previous MI, arrhythmia on Holter monitoring, insulin treatment, and impaired left ventricular ejection fraction (LVEF) ≤30%. RESULTS During follow-up, 83 of the 481 patients (17.3%) died. Of these, 24 deaths were sudden cardiac deaths and 21 nonsudden cardiac deaths. SAF identified a high-risk group of 58 patients with a 5-year mortality rate of 64.0% at a sensitivity level of 38.0%. Multivariately, SAF was the strongest predictor of mortality (hazard ratio 4.9 [95% CI 2.4–9.9]), followed by age ≥65 years (3.4 [1.9–5.8]), and LVEF ≤30% (2.6 [1.5–4.4]). CONCLUSIONS Combined abnormalities of autonomic reflex function and autonomic tonic activity identifies diabetic postinfarction patients with very poor prognoses. PMID:21680727

  10. Lake Layers: Stratification.

    ERIC Educational Resources Information Center

    Brothers, Chris; And Others

    This teacher guide and student workbook set contains two learning activities, designed for fifth through ninth grade students, that concentrate on lake stratification and water quality. In the activities students model the seasonal temperature changes that occur in temperate lakes and observe the resulting stratification of lake waters. Students…

  11. Stratification-score matching improves correction for confounding by population stratification in case-control association studies.

    PubMed

    Epstein, Michael P; Duncan, Richard; Broadaway, K Alaine; He, Min; Allen, Andrew S; Satten, Glen A

    2012-04-01

    Proper control of confounding due to population stratification is crucial for valid analysis of case-control association studies. Fine matching of cases and controls based on genetic ancestry is an increasingly popular strategy to correct for such confounding, both in genome-wide association studies (GWASs) as well as studies that employ next-generation sequencing, where matching can be used when selecting a subset of participants from a GWAS for rare-variant analysis. Existing matching methods match on measures of genetic ancestry that combine multiple components of ancestry into a scalar quantity. However, we show that including nonconfounding ancestry components in a matching criterion can lead to inaccurate matches, and hence to an improper control of confounding. To resolve this issue, we propose a novel method that assigns cases and controls to matched strata based on the stratification score (Epstein et al. [2007] Am J Hum Genet 80:921-930), which is the probability of disease given genomic variables. Matching on the stratification score leads to more accurate matches because case participants are matched to control participants who have a similar risk of disease given ancestry information. We illustrate our matching method using the African-American arm of the GAIN GWAS of schizophrenia. In this study, we observe that confounding due to stratification can be resolved by our matching approach but not by other existing matching procedures. We also use simulated data to show our novel matching approach can provide a more appropriate correction for population stratification than existing matching approaches. PMID:22714934

  12. Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer.

    PubMed

    Fakhry, Carole; Qualliotine, Jesse R; Zhang, Zhe; Agrawal, Nishant; Gaykalova, Daria A; Bishop, Justin A; Subramaniam, Rathan M; Koch, Wayne M; Chung, Christine H; Eisele, David W; Califano, Joseph; Viscidi, Raphael P

    2016-02-01

    Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 early antibody titers E6, E7, E1, and E2 decrease after treatment of HPV16-positive OPC. Trends in pretreatment, early (≤6 months after treatment), and late posttreatment (>6 months after treatment) HPV16 antibody titers were examined. There were 43, 34, and 52 subjects with serum samples available for pretreatment, early, and late posttreatment intervals. Mean pretreatment antibody levels were higher than posttreatment antibody levels. Average antibody levels decreased significantly over time for E6 (Ptrend = 0.001) and E7 (Ptrend < 0.001). Six disease recurrences were observed during the follow-up period (median, 4.4 years). In univariate analysis, a log-unit increase in pretreatment E6 titer was significantly associated with increased risk of disease recurrence (HR, 5.42; 95% CI, 1.1-25.7; P = 0.03). Therefore, levels of antibodies to HPV16 early oncoproteins decline after therapy. Higher E6 titers at diagnosis are associated with significant increases in the risk of recurrence. These data support the prospective evaluation of HPV16 antibodies as markers of surveillance and for risk stratification at diagnosis. PMID:26701665

  13. Unilateral Prostate Cancer Cannot be Accurately Predicted in Low-Risk Patients

    SciTech Connect

    Isbarn, Hendrik; Karakiewicz, Pierre I.; Vogel, Susanne

    2010-07-01

    Purpose: Hemiablative therapy (HAT) is increasing in popularity for treatment of patients with low-risk prostate cancer (PCa). The validity of this therapeutic modality, which exclusively treats PCa within a single prostate lobe, rests on accurate staging. We tested the accuracy of unilaterally unremarkable biopsy findings in cases of low-risk PCa patients who are potential candidates for HAT. Methods and Materials: The study population consisted of 243 men with clinical stage {<=}T2a, a prostate-specific antigen (PSA) concentration of <10 ng/ml, a biopsy-proven Gleason sum of {<=}6, and a maximum of 2 ipsilateral positive biopsy results out of 10 or more cores. All men underwent a radical prostatectomy, and pathology stage was used as the gold standard. Univariable and multivariable logistic regression models were tested for significant predictors of unilateral, organ-confined PCa. These predictors consisted of PSA, %fPSA (defined as the quotient of free [uncomplexed] PSA divided by the total PSA), clinical stage (T2a vs. T1c), gland volume, and number of positive biopsy cores (2 vs. 1). Results: Despite unilateral stage at biopsy, bilateral or even non-organ-confined PCa was reported in 64% of all patients. In multivariable analyses, no variable could clearly and independently predict the presence of unilateral PCa. This was reflected in an overall accuracy of 58% (95% confidence interval, 50.6-65.8%). Conclusions: Two-thirds of patients with unilateral low-risk PCa, confirmed by clinical stage and biopsy findings, have bilateral or non-organ-confined PCa at radical prostatectomy. This alarming finding questions the safety and validity of HAT.

  14. Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis

    PubMed Central

    Asayama, Kei; Thijs, Lutgarde; Brguljan-Hitij, Jana; Niiranen, Teemu J.; Hozawa, Atsushi; Boggia, José; Aparicio, Lucas S.; Hara, Azusa; Johansson, Jouni K.; Ohkubo, Takayoshi; Tzourio, Christophe; Stergiou, George S.; Sandoya, Edgardo; Tsuji, Ichiro; Jula, Antti M.; Imai, Yutaka; Staessen, Jan A.

    2014-01-01

    Background The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP). Methods and Findings This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100. Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries. Conclusions HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased

  15. EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management.

    PubMed

    Castillo, Jorge J; Beltran, Brady E; Miranda, Roberto N; Young, Ken H; Chavez, Julio C; Sotomayor, Eduardo M

    2016-05-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV-positive DLBCL can be seen in younger, immunocompetent patients. The diagnosis of EBV-positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The International Prognostic Index (IPI), and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Patients with EBV-positive DLBCL should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. It has been suggested, however, that EBV-positive patients have a worse prognosis than EBV-negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV-positive DLBCL. Am. J. Hematol. 91:530-537, 2016. © 2016 Wiley Periodicals, Inc. PMID:27093913

  16. Stratification of risk to the surgical team in removal of small arms ammunition implanted in the craniofacial region: case report.

    PubMed

    Forbes, Jonathan A; Laughlin, Ian; Newberry, Shane; Ryhn, Michael; Pasley, Jason; Newberry, Travis

    2016-09-01

    In cases of penetrating injury with implantation of small arms ammunition, it can often be difficult to tell the difference between simple ballistics and ballistics associated with unexploded ordnances (UXOs). In the operative environment, where highly flammable substances are often close to the surgical site, detonation of UXOs could have catastrophic consequences for both the patient and surgical team. There is a paucity of information in the literature regarding how to evaluate whether an implanted munition contains explosive material. This report describes a patient who presented during Operation Enduring Freedom with an implanted munition suspicious for a UXO and the subsequent workup organized by Explosive Ordnance Disposal (EOD) Company prior to surgical removal. Clinical risk factors for UXOs include assassination attempts and/or wartime settings. Specific radiological features suggestive of a UXO include projectile size greater than 7.62-mm caliber, alterations in density of the tip, as well as radiological evidence of a hollowed-out core. If an implanted UXO is suspected, risks to the surgical and anesthesia teams can be minimized by notifying the nearest military installation with EOD capabilities and following clinical practice guidelines set forth by the Joint Theater Trauma System. PMID:26832604

  17. Comparison of Cardiac and Non-Cardiac Biomarkers for Risk Stratification in Elderly Patients with Non-Massive Pulmonary Embolism

    PubMed Central

    Méan, Marie; Limacher, Andreas; Lescuyer, Pierre; Gerstel, Eric; Bounameaux, Henri; Aujesky, Drahomir; Righini, Marc

    2016-01-01

    Biomarkers unrelated to myocardial necrosis, such as cystatin C, copeptin, and mid-regional pro-adrenomedullin (MR-proADM), showed promise for cardiovascular risk prediction. Knowing whether they are comparable to cardiac biomarkers such as high-sensitive cardiac-troponin T (hs-cTnT) or N-terminal pro-Brain natriuretic peptide (NT-proBNP) in elderly patients with acute non-massive pulmonary embolism (NMPE) remains elusive. This study aims at comparing the prognostic accuracy of cardiac and non-cardiac biomarkers in patients with NMPE aged ≥65 years over time. In the context of the SWITCO65+ cohort, we evaluated 227 elderly patients with an available blood sample taken within one day from diagnosis. The primary study endpoint was defined as PE-related mortality and the secondary endpoint as PE-related complications. The biomarkers’ predictive ability at 1, 3, 12 and 24 months was determined using C-statistics and Cox regression. For both study endpoints, C-statistics (95% confidence interval) were stable over time for all biomarkers, with the highest value for hs-cTnT, ranging between 0.84 (0.68–1.00) and 0.80 (0.70–0.90) for the primary endpoint, and between 0.74 (0.63–0.86) and 0.65 (0.57–0.73) for the secondary endpoint. For both study endpoints, cardiac biomarkers were found to be independently associated with risk, NT-proBNP displaying a negative predictive value of 100%. Among non-cardiac biomarkers, only copeptin and MR-proADM were independent predictors of PE-related mortality but they were not independent predictors of PE-related complications, and displayed lower negative predictive values. In elderly NMPE patients, cardiac biomarkers appear to be valuable prognostic to identify very low-risk individuals. Trial Registration: ClinicalTrials.gov NCT00973596 PMID:27219621

  18. Morphomic analysis as an aid for preoperative risk stratification in patients undergoing major head and neck cancer surgery

    PubMed Central

    Rinkinen, Jacob; Agarwal, Shailesh; Beauregard, Jeff; Aliu, Oluseyi; Benedict, Matthew; Buchman, Steven R.; Wang, Stewart C.; Levi, Benjamin

    2016-01-01

    Background Patients undergoing major head and neck cancer surgery (MHNCS) may develop significant postoperative complications. To minimize the risk of complications, clinicians often assess multiple measures of preoperative health in terms of medical comorbidities. One emerging method to decrease surgical complications is preoperative assessment of patient frailty measured by specific tissue characteristics. We hypothesize that morphomic characteristics of the temporalis region serve as predictive markers for the development of complications after MHNCS. Methods We performed a retrospective review of 69 patients with available computed tomography (CT) imaging who underwent MHNCS from 2006–2012. To measure temporalis region characteristics, we used morphomic analysis of available preoperative CT scans to map out the region. All available CT scans had been performed as part of the patient’s routine work-up and were not ordered for morphomic analysis. We describe the correlation among temporalis fat pad volume (TFPV), mean zygomatic arch thickness, and incidence of postoperative complications. Results We noted significant difference in the zygomatic bone thickness and TFPV between patients who had medical complications, surgical complications, or total major complications and those who did not. Furthermore, by use of binary logistic regression, our data suggest decreased TFPV and zygomatic arch thickness are stronger predictors of developing postoperative complications than previously studies preoperative characteristics. Conclusions We describe morphomic analysis of the temporalis region in patients undergoing MHNCS to identify patients at risk for complications. Regional anatomic morphology may serve as a marker to objectively determine a patient’s overall health. Use of the temporalis region is appropriate in patients undergoing MHNCS because of the availability of preoperative scans as part of routine work up for head and/or neck cancer. PMID:25456114

  19. Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population

    PubMed Central

    Srikanthan, Krithika; Feyh, Andrew; Visweshwar, Haresh; Shapiro, Joseph I.; Sodhi, Komal

    2016-01-01

    Introduction: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia. Methods: A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1). Results: According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster. Conclusion: Based on the evidence presented within the literature, the

  20. Cardiac magnetic resonance and computed tomography angiography for clinical imaging of stable coronary artery disease. Diagnostic classification and risk stratification

    PubMed Central

    Korosoglou, Grigorios; Giusca, Sorin; Gitsioudis, Gitsios; Erbel, Christian; Katus, Hugo A.

    2014-01-01

    Despite advances in the pharmacologic and interventional treatment of coronary artery disease (CAD), atherosclerosis remains the leading cause of death in Western societies. X-ray coronary angiography has been the modality of choice for diagnosing the presence and extent of CAD. However, this technique is invasive and provides limited information on the composition of atherosclerotic plaque. Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have emerged as promising non-invasive techniques for the clinical imaging of CAD. Hereby, CCTA allows for visualization of coronary calcification, lumen narrowing and atherosclerotic plaque composition. In this regard, data from the CONFIRM Registry recently demonstrated that both atherosclerotic plaque burden and lumen narrowing exhibit incremental value for the prediction of future cardiac events. However, due to technical limitations with CCTA, resulting in false positive or negative results in the presence of severe calcification or motion artifacts, this technique cannot entirely replace invasive angiography at the present time. CMR on the other hand, provides accurate assessment of the myocardial function due to its high spatial and temporal resolution and intrinsic blood-to-tissue contrast. Hereby, regional wall motion and perfusion abnormalities, during dobutamine or vasodilator stress, precede the development of ST-segment depression and anginal symptoms enabling the detection of functionally significant CAD. While CT generally offers better spatial resolution, the versatility of CMR can provide information on myocardial function, perfusion, and viability, all without ionizing radiation for the patients. Technical developments with these 2 non-invasive imaging tools and their current implementation in the clinical imaging of CAD will be presented and discussed herein. PMID:25147526

  1. Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography

    SciTech Connect

    Brown, K.A.; Rimmer, J.; Haisch, C. )

    1989-11-01

    The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events.

  2. Improved Clinical Risk Stratification in Patients with Long QT Syndrome? Novel Insights from Multi-Channel ECGs

    PubMed Central

    Samol, Alexander; Gönes, Mehmet; Zumhagen, Sven; Bruns, Hans-Jürgen; Paul, Matthias; Vahlhaus, Christian; Waltenberger, Johannes; Schulze-Bahr, Eric; Eckardt, Lars; Mönnig, Gerold

    2016-01-01

    Background We investigated whether multichannel ECG-recordings are useful to risk-stratify patients with congenital long-QT syndrome (LQTS) for risk of sudden cardiac death under optimized medical treatment. Methods In 34 LQTS-patients (11 male; age 31±13 years, QTc 478±51ms; LQT1 n = 8, LQT2 n = 15) we performed a standard 12-channel ECG and a 120-channel body surface potential mapping. The occurrence of clinical events (CE; syncope, torsade de pointes (TdP), sudden cardiac arrest (SCA)) was documented and correlated with different ECG-parameters in all lead positions. Results Seven patients developed TdP, four survived SCA and 12 experienced syncope. 12/34 had at least one CE. CE was associated with a longer QTc-interval (519±43ms vs. 458±42ms; p = 0.001), a lower T-wave integral (TWI) on the left upper chest (-1.2±74.4mV*ms vs. 63.0±29.7mV*ms; p = 0.001), a lower range of T-wave amplitude (TWA) in the region of chest lead V8 (0.10±0.08mV vs. 0.18±0.07mV; p = 0.008) and a longer T-peak-T-end time (TpTe) in lead V1 (98±23ms vs. 78±26ms; p = 0.04). Receiver-operating-characteristic (ROC) analyses revealed a sensitivity of 96% and a specificity of 75% (area under curve (AUC) 0.89±0.06, p = 0.001) at a cut-off value of 26.8mV*ms for prediction of CE by TWI, a sensitivity of 86% and a specificity of 83% at a cut-off value of 0.11mV (AUC 0.83±0.09, p = 0.002) for prediction of CE by TWA and a sensitivity of 83% and a specificity of 73% at a cut-off value of 87ms (AUC 0.80±0.07, p = 0.005) for prediction of CE by TpTe. Conclusions Occurrence of CE in LQTS-patients seems to be associated with a prolonged, low-amplitude T-wave. PMID:27379800

  3. Risk stratification of T-cell Acute Lymphoblastic Leukemia patients based on gene expression, mutations and copy number variation.

    PubMed

    Mirji, Gauri; Bhat, Jaydeep; Kode, Jyoti; Banavali, Shripad; Sengar, Manju; Khadke, Prashant; Sait, Osama; Chiplunkar, Shubhada

    2016-06-01

    Gene expression, copy number variations (CNV), mutations and survival were studied to delineate TCRγδ+T-cell acute lymphoblastic leukemia (T-ALL) as a distinct subgroup from TCRαβ+T-ALL. Gene Ontology analysis showed that differential regulation of genes involved in pathways for leukemogenesis, apoptosis, cytokine-cytokine receptor interaction and antigen processing/presentation may offer a survival benefit to TCRγδ+T-ALL patients. Genes involved in disease biology and having equal expression in both the subgroups, were further analysed for mutations and CNV using droplet digital PCR. TCRγδ+T-ALL patients exhibited differential level of mutations for NOTCH1 and IKZF3; however BRAF mutations were detected at equal levels in both the subgroups. Although TCRγδ+T-ALL patients with these mutations demonstrated improved disease-free survival (DFS) as compared TCRαβ+T-ALL patients, it was not statistically significant. Patients with homozygous deletion of CDKN2A/CDKN2B showed poor DFS in each subgroup. TCRγδ+T-ALL patients with wild type/heterozygous deletion of CDKN2A/CDKN2B possess significantly better DFS over TCRαβ+T-ALL patients (p=0.017 and 0.045, respectively). Thus, the present study has for the first time demonstrated TCRγδ clonality and CDKN2A/CDKN2B CNV together as potential prognostic markers in management of T-ALL. Further understanding the functional significance of differentially regulated genes in T-ALL patients would aid in designing risk based treatment strategies in subset specific manner. PMID:27070758

  4. Risk stratification based on change in plasma Epstein-Barr virus DNA load after treatment in nasopharyngeal carcinoma

    PubMed Central

    Mao, Yan-Ping; Guo, Rui; Tang, Ling-Long; Peng, Hao; Sun, Ying; Liu, Qing; Chen, Lei; Ma, Jun

    2016-01-01

    Background: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV). The current study investigated change in the plasma EBV DNA load in the first 3 months after treatment and its clinical significance in NPC. Methods: A total of 273 patients with non-metastatic, histologically-proven NPC treated with radiotherapy or chemoradiotherapy were retrospectively reviewed. Results: EBV DNA was detectable in 19/273 (7.0%) patients at the end of therapy (end-DNA). Three months later, 16/273 (5.9%) patients had detectable EBV DNA (3-month-DNA). To investigate risk stratified by the pattern of change in post-treatment EBV-DNA, we divided patients into four subgroups: Group 1, undetectable end-DNA and 3-month-DNA (n = 244); Group 2, detectable end-DNA and undetectable 3-month-DNA (n = 13); Group 3, undetectable end-DNA and detectable 3-month-DNA (n = 7); and Group 4, detectable end-DNA and 3-month-DNA (n = 2). Patients with delayed remission of EBV DNA after treatment (Group 2) had significantly poorer 3-year DFS (48.6% vs. 89.7%, P < 0.001), DMFS (48.6% vs. 94.6%, P < 0.001) and OS (91.7% vs. 97.5%, P < 0.001) than those with persistently undetectable EBV DNA post-treatment (Group 1). Five of the seven patients with re-emergent EBV DNA (Group 3) and both patients with persistent EBV DNA post-treatment (Group 4) developed disease failure. Conclusion: Plasma EBV DNA load continues to change during the first 3 months after treatment. The pattern of change in EBV DNA load post-treatment could help identify patients with different prognoses. PMID:26840023

  5. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

    PubMed Central

    Ross-Adams, H.; Lamb, A.D.; Dunning, M.J.; Halim, S.; Lindberg, J.; Massie, C.M.; Egevad, L.A.; Russell, R.; Ramos-Montoya, A.; Vowler, S.L.; Sharma, N.L.; Kay, J.; Whitaker, H.; Clark, J.; Hurst, R.; Gnanapragasam, V.J.; Shah, N.C.; Warren, A.Y.; Cooper, C.S.; Lynch, A.G.; Stark, R.; Mills, I.G.; Grönberg, H.; Neal, D.E.

    2015-01-01

    Background Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene

  6. Nonlinear analysis of the heartbeats in public patient ECGs using an automated PD2i algorithm for risk stratification of arrhythmic death

    PubMed Central

    Skinner, James E; Anchin, Jerry M; Weiss, Daniel N

    2008-01-01

    Heart rate variability (HRV) reflects both cardiac autonomic function and risk of arrhythmic death (AD). Reduced indices of HRV based on linear stochastic models are independent risk factors for AD in post-myocardial infarct cohorts. Indices based on nonlinear deterministic models have a significantly higher sensitivity and specificity for predicting AD in retrospective data. A need exists for nonlinear analytic software easily used by a medical technician. In the current study, an automated nonlinear algorithm, the time-dependent point correlation dimension (PD2i), was evaluated. The electrocardiogram (ECG) data were provided through an National Institutes of Health-sponsored internet archive (PhysioBank) and consisted of all 22 malignant arrhythmia ECG files (VF/VT) and 22 randomly selected arrhythmia files as the controls. The results were blindly calculated by automated software (Vicor 2.0, Vicor Technologies, Inc., Boca Raton, FL) and showed all analyzable VF/VT files had PD2i < 1.4 and all analyzable controls had PD2i > 1.4. Five VF/VT and six controls were excluded because surrogate testing showed the RR-intervals to contain noise, possibly resulting from the low digitization rate of the ECGs. The sensitivity was 100%, specificity 85%, relative risk > 100; p < 0.01, power > 90%. Thus, automated heartbeat analysis by the time-dependent nonlinear PD2i-algorithm can accurately stratify risk of AD in public data made available for competitive testing of algorithms. PMID:18728829

  7. Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved left ventricular function (ISAR-Risk)

    PubMed Central

    Bauer, Axel; Barthel, Petra; Schneider, Raphael; Ulm, Kurt; Müller, Alexander; Joeinig, Anke; Stich, Raphael; Kiviniemi, Antti; Hnatkova, Katerina; Huikuri, Heikki; Schömig, Albert; Malik, Marek; Schmidt, Georg

    2009-01-01

    Aims To investigate the combination of heart rate turbulence (HRT) and deceleration capacity (DC) as risk predictors in post-infarction patients with left ventricular ejection fraction (LVEF) > 30%. Methods and results We enrolled 2343 consecutive survivors of acute myocardial infarction (MI) (<76 years) in sinus rhythm. HRT and DC were obtained from 24 h Holter recordings. Patients with both abnormal HRT (slope ≤ 2.5 ms/RR and onset ≥ 0%) and abnormal DC (≤4.5 ms) were considered suffering from severe autonomic failure (SAF) and prospectively classified as high risk. Primary and secondary endpoints were all-cause, cardiac, and sudden cardiac mortality within the first 5 years of follow-up. During follow-up, 181 patients died; 39 deaths occurred in 120 patients with LVEF ≤ 30%, and 142 in 2223 patients with LVEF>30% (cumulative 5-year mortality rates of 37.9% and 7.8%, respectively). Among patients with LVEF > 30%, SAF identified another high-risk group of 117 patients with 37 deaths (cumulative 5-year mortality rates of 38.6% and 6.1%, respectively). Merging both high-risk groups (i.e. LVEF ≤ 30% and/or SAF) doubled the sensitivity of mortality prediction compared with LVEF ≤ 30% alone (21.1% vs. 42.1%, P < 0.001) while preserving 5-year mortality rate (38.2%). Conclusion In post-MI patients with LVEF>30%, SAF identifies a high-risk group equivalent in size and mortality risk to patients with LVEF ≤ 30%. PMID:19109245

  8. Migration and stratification

    PubMed Central

    Jasso, Guillermina

    2011-01-01

    Migration and stratification are increasingly intertwined. One day soon it will be impossible to understand one without the other. Both focus on life chances. Stratification is about differential life chances - who gets what and why - and migration is about improving life chances - getting more of the good things of life. To examine the interconnections of migration and stratification, we address a mix of old and new questions, carrying out analyses newly enabled by a unique new data set on recent legal immigrants to the United States (the New Immigrant Survey). We look at immigrant processing and lost documents, depression due to the visa process, presentation of self, the race-ethnic composition of an immigrant cohort (made possible by the data for the first time since 1961), black immigration from Africa and the Americas, skin-color diversity among couples formed by U.S. citizen sponsors and immigrant spouses, and English fluency among children age 8–12 and their immigrant parents. We find, inter alia, that children of previously illegal parents are especially more likely to be fluent in English, that native-born U.S. citizen women tend to marry darker, that immigrant applicants who go through the visa process while already in the United States are more likely to have their documents lost and to suffer visa depression, and that immigration, by introducing accomplished black immigrants from Africa (notably via the visa lottery), threatens to overturn racial and skin color associations with skill. Our analyses show the mutual embeddedness of migration and stratification in the unfolding of the immigrants' and their children's life chances and the impacts on the stratification structure of the United States. PMID:26321771

  9. Towards more accurate life cycle risk management through integration of DDP and PRA

    NASA Technical Reports Server (NTRS)

    Cornford, Steven L.; Paulos, Todd; Meshkat, Leila; Feather, Martin

    2003-01-01

    The focus of this paper is on the integration of PRA and DDP. The intent is twofold: to extend risk-based decision though more of the lifecycle, and to lead to improved risk modeling (hence better informed decision making) wherever it is applied, most especially in the early phases as designs begin to mature.

  10. Simplified risk stratification criteria for identification of patients with MRSA bacteremia at low risk of infective endocarditis: implications for avoiding routine transesophageal echocardiography in MRSA bacteremia.

    PubMed

    Buitron de la Vega, P; Tandon, P; Qureshi, W; Nasr, Y; Jayaprakash, R; Arshad, S; Moreno, D; Jacobsen, G; Ananthasubramaniam, K; Ramesh, M; Zervos, M

    2016-02-01

    The aim of this study was to identify patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with low risk of infective endocarditis (IE) who might not require routine trans-esophageal echocardiography (TEE). We retrospectively evaluated 398 patients presenting with MRSA bacteremia for the presence of the following clinical criteria: intravenous drug abuse (IVDA), long-term catheter, prolonged bacteremia, intra-cardiac device, prosthetic valve, hemodialysis dependency, vertebral/nonvertebral osteomyelitis, cardio-structural abnormality. IE was diagnosed using the modified Duke criteria. Of 398 patients with MRSA bacteremia, 26.4 % of cases were community-acquired, 56.3 % were health-care-associated, and 17.3 % were hospital-acquired. Of the group, 44 patients had definite IE, 119 had possible IE, and 235 had a rejected diagnosis. Out of 398 patients, 231 were evaluated with transthoracic echocardiography (TTE) or TEE. All 44 patients with definite IE fulfilled at least one criterion (sensitivity 100 %). Finally, a receiver operator characteristic (ROC) curve was obtained to evaluate the total risk score of our proposed criteria as a predictor of the presence of IE, and this was compared to the ROC curve of a previously proposed criteria. The area under the ROC curve for our criteria was 0.710, while the area under the ROC curve for the criteria previously proposed was 0.537 (p < 0.001). The p-value for comparing those 2 areas was less than 0.001, indicating statistical significance. Patients with MRSA bacteremia without any of our proposed clinical criteria have very low risk of developing IE and may not require routine TEE. PMID:26676855

  11. SBRT for the Primary Treatment of Localized Prostate Cancer: The Effect of Gleason Score, Dose and Heterogeneity of Intermediate Risk on Outcome Utilizing 2.2014 NCCN Risk Stratification Guidelines

    PubMed Central

    Bernetich, Matthew; Oliai, Caspian; Lanciano, Rachelle; Hanlon, Alexandra; Lamond, John; Arrigo, Stephen; Yang, Jun; Good, Michael; Feng, Jing; Brown, Royce; Garber, Bruce; Mooreville, Michael; Brady, Luther W.

    2014-01-01

    Purpose: To report an update of our previous experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer, risk stratified by the updated National Comprehensive Cancer Network (NCCN) version 2.2014, reporting efficacy and toxicity in a community hospital setting. Methods: From 2007 to 2012, 142 localized prostate cancer patients were treated with SBRT using CyberKnife. NCCN guidelines Version 2.2014 risk groups analyzed included very low (20%), low (23%), intermediate (35%), and high (22%) risk. To further explore group heterogeneity and to comply with new guidelines, we separated our prior intermediate risk group into favorable intermediate and unfavorable intermediate groups depending on how many intermediate risk factors were present (one vs. > one). The unfavorable intermediate group was further analyzed in combination with the high risk group as per NCCN guidelines Version 2.2014. Various dose levels were used over the years of treatment, and have been categorized into low dose (35 Gy, n = 5 or 36.25 Gy, n = 107) and high dose (37.5 Gy, n = 30). All treatments were delivered in five fractions. Toxicity was assessed using radiation therapy oncology group criteria. Results: Five-year actuarial freedom from biochemical failure (FFBF) was 100, 91.7, 95.2, 90.0, and 86.7% for very low, low, intermediate and high risk patients, respectively. A significant difference in 5 year FFBF was noted for patients with Gleason score (GS) ≥8 vs. 7 vs. 5/6 (p = 0.03) and low vs. high dose (p = 0.05). T-stage, pretreatment PSA, age, risk stratification group, and use of ADT did not affect 5-year FFBF. Multivariate analysis revealed GS and dose to be the most predictive factors for 5-year FFBF. Conclusion: Our experience with SBRT for the primary treatment of localized prostate cancer demonstrates favorable efficacy and toxicity comparable to the results reported for IMRT in literature. GS remains the

  12. Role of risk stratification by SPECT, PET, and hybrid imaging in guiding management of stable patients with ischaemic heart disease: expert panel of the EANM cardiovascular committee and EACVI.

    PubMed

    Acampa, Wanda; Gaemperli, Oliver; Gimelli, Alessia; Knaapen, Paul; Schindler, Thomas H; Verberne, Hein J; Zellweger, Michael J

    2015-12-01

    Risk stratification has become increasingly important in the management of patients with suspected or known ischaemic heart disease (IHD). Recent guidelines recommend that these patients have their care driven by risk assessment. The purpose of this position statement is to summarize current evidence on the value of cardiac single-photon emission computed tomography, positron emission tomography, and hybrid imaging in risk stratifying asymptomatic or symptomatic patients with suspected IHD, patients with stable disease, patients after coronary revascularization, heart failure patients, and specific patient population. In addition, this position statement evaluates the impact of imaging results on clinical decision-making and thereby its role in patient management. The document represents the opinion of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee and of the European Association of Cardiovascular Imaging (EACVI) and intends to stimulate future research in this field. PMID:25902767

  13. Accurately Predicting Future Reading Difficulty for Bilingual Latino Children at Risk for Language Impairment

    ERIC Educational Resources Information Center

    Petersen, Douglas B.; Gillam, Ronald B.

    2013-01-01

    Sixty-three bilingual Latino children who were at risk for language impairment were administered reading-related measures in English and Spanish (letter identification, phonological awareness, rapid automatized naming, and sentence repetition) and descriptive measures including English language proficiency (ELP), language ability (LA),…

  14. TIMP2•IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients

    PubMed Central

    Gunnerson, Kyle J.; Shaw, Andrew D.; Chawla, Lakhmir S.; Bihorac, Azra; Al-Khafaji, Ali; Kashani, Kianoush; Lissauer, Matthew; Shi, Jing; Walker, Michael G.; Kellum, John A.

    2016-01-01

    BACKGROUND Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2•IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI. STUDY DESIGN We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2–3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement. RESULTS A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]•[IGFBP7] alone was 0.84 (95% confidence interval, 0.76–0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery). CONCLUSION For postoperative surgical intensive care unit patients, a single urinary TIMP2•IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance. LEVEL OF EVIDENCE Prognostic study, level I. PMID:26816218

  15. Development and Validation of a Risk Stratification Score for Ventral Incisional Hernia after Abdominal Surgery: Hernia Expectation Rates iN Intra-Abdominal Surgery (The HERNIA Project)

    PubMed Central

    Goodenough, Christopher J; Ko, Tien C; Kao, Lillian S; Nguyen, Mylan T; Holihan, Julie L; Alawadi, Zeinab; Nguyen, Duyen H; Gonzalez, Juan Ramon; Arita, Nestor T; Roth, J Scott; Liang, Mike K

    2015-01-01

    Background Ventral incisional hernias (VIH) develop in up to 20% of patients following abdominal surgery. No widely applicable pre-operative risk-assessment tool exists. We aim to develop and validate a risk-assessment tool to predict VIH following abdominal surgery. Study Design A prospective study of all patients undergoing abdominal surgery was conducted at a single institution from 2008-2010. Variables were defined in accordance with the National Surgical Quality Improvement Project. VIH was determined through clinical and radiographic evaluation. A multivariate Cox proportional hazard model was built from a development cohort (2008-2009) to identify predictors of VIH. The HERNIAscore was created by converting the hazards ratios (HR) to points. The predictive accuracy was assessed on the validation cohort (2010) using a receiver operator characteristic curve and calculating the area under the curve (AUC). Results Of 625 patients followed for a median of 41(0.3-64 months), 93(13.9%) developed a VIH. The training cohort (n=428, VIH=70,16.4%) identified four independent predictors: laparotomy (HR 4.77, 95%CI 2.61-8.70) or hand-assisted laparoscopy (HR=4.00, 95% CI 2.08-7.70), COPD (HR=2.35; 95%CI 1.44-3.83), and BMI≥25 (HR=1.74; 95% CI 1.04-2.91). Factors that were not predictive included age, gender, ASA score, albumin, immunosuppression, prior surgery, and suture material/technique. The predictive score had an AUC=0.77(95%CI0.68-0.86) using the validation cohort (n=197, VIH=23,11.6%). Using the HERNIAscore--HERNIAscore=4*Laparotomy+3*HAL+1*COPD+1* BMI≥25--three classes stratified the risk of VIH: Class I (0-3 points):5.2%, Class II (4-5 points):19.6%, and Class III (6 points):55.0%. Conclusions The HERNIAscore accurately identifies patients at increased risk for VIH. While external validation is needed, this provides a starting point to counsel patients and guide clinical decisions. Increasing the use of laparoscopy, weight-loss programs, community smoking

  16. A rapid, economical, and accurate method to determining the physical risk of storm marine inundations using sedimentary evidence

    NASA Astrophysics Data System (ADS)

    Nott, Jonathan F.

    2015-04-01

    The majority of physical risk assessments from storm surge inundations are derived from synthetic time series generated from short climate records, which can often result in inaccuracies and are time-consuming and expensive to develop. A new method is presented here for the wet tropics region of northeast Australia. It uses lidar-generated topographic cross sections of beach ridge plains, which have been demonstrated to be deposited by marine inundations generated by tropical cyclones. Extreme value theory statistics are applied to data derived from the cross sections to generate return period plots for a given location. The results suggest that previous methods to estimate return periods using synthetic data sets have underestimated the magnitude/frequency relationship by at least an order of magnitude. The new method promises to be a more rapid, economical, and accurate assessment of the physical risk of these events.

  17. Risk stratification algorithm for management of patients with dual modular taper total hip arthroplasty: consensus statement of the American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons and the Hip Society.

    PubMed

    Kwon, Young-Min; Fehring, Thomas K; Lombardi, Adolph V; Barnes, C Lowry; Cabanela, Miguel E; Jacobs, Joshua J

    2014-11-01

    Although 'dual taper' modular stems with interchangeable modular necks have the potential to optimize hip biomechanical parameters, there is increasing concern regarding the occurrence of adverse local tissue reactions from mechanically assisted crevice corrosion at the neck-stem taper junction. A systematic treatment approach (risk stratification algorithm) based on the currently available data is recommended to optimize patient management. While specialized tests such as metal ion analysis and MARS MRI are useful modalities in evaluating for adverse tissue reactions, over-reliance on any single investigative tool in the clinical decision-making process should be avoided. There should be a low threshold to perform a systematic evaluation of patients with dual taper stem total hip arthroplasty as early recognition and diagnosis will facilitate the initiation of appropriate treatment. PMID:25189673

  18. Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia.

    PubMed

    Buccisano, Francesco; Maurillo, Luca; Spagnoli, Alessandra; Del Principe, Maria Ilaria; Fraboni, Daniela; Panetta, Paola; Ottone, Tiziana; Consalvo, Maria Irno; Lavorgna, Serena; Bulian, Pietro; Ammatuna, Emanuele; Angelini, Daniela F; Diamantini, Adamo; Campagna, Selenia; Ottaviani, Licia; Sarlo, Chiara; Gattei, Valter; Del Poeta, Giovanni; Arcese, William; Amadori, Sergio; Lo Coco, Francesco; Venditti, Adriano

    2010-09-30

    A total of 143 adult acute myeloid leukemia (AML) patients with available karyotype (K) and FLT3 gene mutational status were assessed for minimal residual disease (MRD) by flow cytometry. Twenty-two (16%) patients had favorable, 115 (80%) intermediate, and 6 (4%) poor risk K; 19 of 129 (15%) carried FLT3-ITD mutation. Considering postconsolidation MRD status, patients with good/intermediate-risk K who were MRD(-) had 4-year relapse-free survival (RFS) of 70% and 63%, and overall survival (OS) of 84% and 67%, respectively. Patients with good- and intermediate-risk K who were MRD(+) had 4-year RFS of 15% and 17%, and OS of 38% and 23%, respectively (P < .001 for all comparisons). FLT3 wild-type patients achieving an MRD(-) status, had a better outcome than those who remained MRD(+) (4-year RFS, 54% vs 17% P < .001; OS, 60% vs 23%, P = .002). Such an approach redefined cytogenetic/genetic categories in 2 groups: (1) low-risk, including good/intermediate K-MRD(-) with 4-year RFS and OS of 58% and 73%, respectively; and (2) high risk, including poor-risk K, FLT3-ITD mutated cases, good/intermediate K-MRD(+) categories, with RFS and OS of 22% and 17%, respectively (P < .001 for all comparisons). In AML, the integrated evaluation of baseline prognosticators and MRD improves risk-assessment and optimizes postremission therapy. PMID:20548095

  19. Stratification requirements for seed dormancy alleviation in a wetland weed.

    PubMed

    Boddy, Louis G; Bradford, Kent J; Fischer, Albert J

    2013-01-01

    Echinochloaoryzicola(syn.E. phyllopogon) is an exotic weed of California rice paddies that has evolved resistance to multiple herbicides. Elimination of seedlingsthroughcertain weed control methods can limit the spread of this weed, but is contingent on accurate predictions of germination and emergence timing, which are influenced by seed dormancy levels.In summer annuals, dormancy can often be relieved through stratification, a period of prolonged exposure to cold and moist conditions.We used population-based threshold models to quantify the effects of stratification on seed germination of four E. Oryzicola populations at a range of water potential (Ψ) and oxygen levels. We also determined how stratification temperatures, moisture levels and durations contributed to dormancy release. Stratification released dormancy by decreasing base Ψ and hydrotimerequired for germination and by eliminating any germination sensitivity to oxygen. Stratification also increased average germination rates (GR), which were used as a proxy for relative dormancy levels. Alternating temperatures nearly doubled GR in all populations, indicating that seeds could be partially dormant despite achieving high final germination percentages. Stratification at Ψ = 0 MPa increased GR compared to stratification at lower water potentials, demonstrating that Ψ contributed to regulating dormancy release. Maximum GR occurred after 2-4 weeks of stratification at 0 MPa; GR were often more rapid for herbicide-resistant than for herbicide-susceptible seeds, implying greater dormancy in the latter. Manipulation of field conditions to promote dormancy alleviation of E. oryzicola seeds might improve the rate and uniformity of germination for seed bank depletion through seedling weed control. Our results suggest field soil saturation in winter would contribute towards E. oryzicola dormancy release and decrease the time to seedling emergence. PMID:24039714

  20. Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification

    PubMed Central

    Jedrzkiewicz, Sean; Goodman, Shaun G; Yan, Raymond T; Welsh, Robert C; Kornder, Jan; DeYoung, J Paul; Wong, Graham C; Rose, Barry; Grondin, François R; Gallo, Richard; Huang, Wei; Gore, Joel M; Yan, Andrew T

    2009-01-01

    BACKGROUND: Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada. OBJECTIVE: To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS. METHODS: Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment. RESULTS: While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization. CONCLUSION: Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada. PMID:19898699

  1. Novel and Convenient Method to Evaluate the Character of Solitary Pulmonary Nodule-Comparison of Three Mathematical Prediction Models and Further Stratification of Risk Factors

    PubMed Central

    Xiao, Fei; Liu, Deruo; Guo, Yongqing; Shi, Bin; Song, Zhiyi; Tian, Yanchu; Liang, Chaoyang

    2013-01-01

    Objective To study risk factors that affect the evaluation of malignancy in patients with solitary pulmonary nodules (SPN) and verify different predictive models for malignant probability of SPN. Methods Retrospectively analyzed 107 cases of SPN with definite post-operative histological diagnosis whom underwent surgical procedures in China-Japan Friendship Hospital from November of 2010 to February of 2013. Age, gender, smoking history, malignancy history of patients, imaging features of the nodule including maximum diameter, position, spiculation, lobulation, calcification and serum level of CEA and Cyfra21-1 were assessed as potential risk factors. Univariate analysis model was used to establish statistical correlation between risk factors and post-operative histological diagnosis. Receiver operating characteristic (ROC) curves were drawn using different predictive models for malignant probability of SPN to get areas under the curves (AUC values), sensitivity, specificity, positive predictive values, negative predictive values for each model, respectively. The predictive effectiveness of each model was statistically assessed subsequently. Results In 107 patients, 78 cases were malignant (72.9%), 29 cases were benign (27.1%). Statistical significant difference was found between benign and malignant group in age, maximum diameter, serum level of Cyfra21-1, spiculation, lobulation and calcification of the nodules. The AUC values were 0.786±0.053 (Mayo model), 0.682±0.060 (VA model) and 0.810±0.051 (Peking University People’s Hospital model), respectively. Conclusions Serum level of Cyfra21-1, patient’s age, maximum diameter of the nodule, spiculation, lobulation and calcification of the nodule are independent risk factors associated with the malignant probability of SPN. Peking University People’s Hospital model is of high accuracy and clinical value for patients with SPN. Adding serum index (e.g. Cyfra21-1) into the prediction models as a new risk factor

  2. Risk of Malignant Neoplasms of Kidney and Bladder in a Cohort Study of the Diabetic Population in Taiwan With Age, Sex, and Geographic Area Stratifications

    PubMed Central

    Chen, Hua-Fen; Chen, Shwe-Winn; Chang, Ya-Hui; Li, Chung-Yi

    2015-01-01

    Abstract Diabetes has been reported to increase the risk of malignant neoplasms of kidney and bladder, but the studies’ results are still inconclusive. Age, sex, and geographical area-specific incidence and relative risks of above neoplasms are also scarce in the literature. We prospectively investigated the age, sex, geographical area-specific incidence and relative risks of kidney and bladder neoplasms in diabetic population of Taiwan. Diabetic patients (n = 615,532) and age- and sex-matched controls (n = 614,871) were linked to inpatient claims (2000–2008) to identify the admissions for malignant neoplasm of kidney (International Classification of Diagnosis, 9th version, Clinical Modification: 189) and bladder (International Classification of Diagnosis, 9th version, Clinical Modification: 188). The person-year approach with Poisson assumption was used to evaluate the incidence density. We also estimated the age, sex, and geographical area-specific relative risks of above malignancy in relation to diabetes with Cox proportional hazard regression model. The overall incidence density of malignant neoplasm of kidney for diabetic men and women were 3.87 and 4.28 per 10,000 patient-years, respectively; the corresponding figures for malignant neoplasm of bladder were 5.73 and 3.25 per 10,000 patient-years. Compared with the controls, diabetic men were at significantly increased hazards of kidney (covariate adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI] 1.18–1.46) and bladder aHR: 1.13, 95% CI 1.04–1.23). Diabetic women, on the contrary, only experienced significantly elevated hazard of kidney neoplasm (aHR: 1.14, 95% CI 1.04–1.26). Diabetic men aged >65 years showed the most significantly increased hazard of developing neoplasm of kidney (aHR: 1.40) and bladder (aHR: 1.13). The most significantly increased hazard of kidney neoplasm was noted for women diabetic patients aged >65 years. There was also a significant interactive effect of

  3. Management of Newly Diagnosed Symptomatic Multiple Myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines

    PubMed Central

    Kumar, Shaji K.; Mikhael, Joseph R.; Buadi, Francis K.; Dingli, David; Dispenzieri, Angela; Fonseca, Rafael; Gertz, Morie A.; Greipp, Philip R.; Hayman, Suzanne R.; Kyle, Robert A.; Lacy, Martha Q.; Lust, John A.; Reeder, Craig B.; Roy, Vivek; Russell, Stephen J.; Short, Kristen E. Detweiler; Stewart, A. Keith; Witzig, Thomas E.; Zeldenrust, Steven R.; Dalton, Robert J.; Rajkumar, S. Vincent; Bergsagel, P. Leif

    2009-01-01

    Multiple myeloma is a malignant plasma cell neoplasm that affects more than 20,000 people each year and is the second most common hematologic malignancy. It is part of a spectrum of monoclonal plasma cell disorders, many of which do not require active therapy. During the past decade, considerable progress has been made in our understanding of the disease process and factors that influence outcome, along with development of new drugs that are highly effective in controlling the disease and prolonging survival without compromising quality of life. Identification of well-defined and reproducible prognostic factors and introduction of new therapies with unique modes of action and impact on disease outcome have for the first time opened up the opportunity to develop risk-adapted strategies for managing this disease. Although these risk-adapted strategies have not been prospectively validated, enough evidence can be gathered from existing randomized trials, subgroup analyses, and retrospective studies to develop a working framework. This set of recommendations represents such an effort—the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence. PMID:19955246

  4. Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

    PubMed Central

    Melgaard, Line; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y. H.; Larsen, Torben Bjerregaard

    2016-01-01

    Background Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI). Methods Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease. Results 39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes. Conclusions Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD. PMID:27015524

  5. Innovative tools for assessing risks for severe adverse events in areas of overlapping Loa loa and other filarial distributions: the application of micro-stratification mapping

    PubMed Central

    2014-01-01

    Background The wide distribution of Loa loa infection (loiasis) throughout the Democratic Republic of Congo (DRC) is a major obstacle to the plans to eliminate onchocerciasis and lymphatic filariasis (LF) because the standard drug regime is dependent on ivermectin, which cannot be used in co-endemic areas due to the risk of severe adverse events (SAEs). A better understanding of the micro-epidemiology, overlapping low and high risk areas, and how they relate to SAEs is critical to ensure safe and effective treatment. Findings Based on published data from the Bas Congo Province in DRC, this study used geographical information systems (GIS) to re-map and analyse onchocerciasis and loiasis prevalence (<20%, 20 to 40%, >40%) at 144 sites in relation to health district areas reporting SAEs. The new maps highlighted the contrasting patterns of the high prevalence sites, and significant geographical overlap between low onchocerciasis and high loiasis sites. Statistical analyses found that sites with medium to high loiasis prevalence were 10 to 16 times more likely to be in a SAE area than those with low prevalence of loiasis. Sites where both onchocerciasis and loiasis prevalence was >20% were also associated with SAE areas. Conclusions Collaborative efforts between the national onchocerciasis and LF programmes are critical as plans to scale interventions are moving forward and thus, alternative strategies needed in loiasis co-endemic areas which may include the new L. loa test and treat strategy using the Cellscope, or interventions such as integrated vector management, or anti Wolbachia therapy using doxycycline. PMID:24992829

  6. Automated detection of dual p16/Ki67 nuclear immunoreactivity in liquid-based Pap tests for improved cervical cancer risk stratification

    PubMed Central

    Gertych, Arkadiusz; Joseph, Anika O.; Walts, Ann E.; Bose, Shikha

    2012-01-01

    The Papanicolau (Pap) test is a routine cytological procedure for early detection of dysplastic lesions in cervical epithelium. A reliable screening method is crucial for triage of women at risk; however manual screening and interpretation are associated with relatively low sensitivity and substantial interobserver diagnostic variability. P16 and Ki67 biomarkers have been recently proposed as adjunctive tools in the diagnosis of high-risk human papillomavirus (hrHPV) associated dysplasias to supplement the morphological characteristics of cells by additional colorimetric features. In this study, an automated technique for the evaluation of dual p16/Ki67 immunoreactivity in cervical cell nuclei is introduced. Smears stained with p16 and Ki67 antibodies were digitized, and analyzed by algorithms we developed. Gradient-based radial symmetry operator and adaptive processing of symmetry image were employed to obtain the nuclear mask. This step was followed by the extraction of features including pixel data and immunoreactivity signature from each nucleus. The features were analyzed by two support vector machine classifiers to assign a nucleus into one of four types of immunoreactivity: p16 positive (p16+/Ki67-), Ki67 positive (p16-/Ki67+), dual p16/Ki67 positive (p16+/Ki67+) and negative (p16-/Ki67-) respectively. Results obtained by our method correlated well with readings by two cytopathologists (n=18068 cells); p16+/Ki67+ nuclei were classified with respective precisions of 77.1% and 82.6%. Specificity in identification of p16-/Ki67- nuclei was better than 99.5%, and the sensitivity in detection of all immunopositive nuclei was 86.3% and 89.4% respectively. We found that the quantitative characterization of immunoreactivity provided by the additional highlighting of classified nuclei can positively impact the efficacy and screening outcome of the Pap test. PMID:22215277

  7. SU-E-J-208: Fast and Accurate Auto-Segmentation of Abdominal Organs at Risk for Online Adaptive Radiotherapy

    SciTech Connect

    Gupta, V; Wang, Y; Romero, A; Heijmen, B; Hoogeman, M; Myronenko, A; Jordan, P

    2014-06-01

    Purpose: Various studies have demonstrated that online adaptive radiotherapy by real-time re-optimization of the treatment plan can improve organs-at-risk (OARs) sparing in the abdominal region. Its clinical implementation, however, requires fast and accurate auto-segmentation of OARs in CT scans acquired just before each treatment fraction. Autosegmentation is particularly challenging in the abdominal region due to the frequently observed large deformations. We present a clinical validation of a new auto-segmentation method that uses fully automated non-rigid registration for propagating abdominal OAR contours from planning to daily treatment CT scans. Methods: OARs were manually contoured by an expert panel to obtain ground truth contours for repeat CT scans (3 per patient) of 10 patients. For the non-rigid alignment, we used a new non-rigid registration method that estimates the deformation field by optimizing local normalized correlation coefficient with smoothness regularization. This field was used to propagate planning contours to repeat CTs. To quantify the performance of the auto-segmentation, we compared the propagated and ground truth contours using two widely used metrics- Dice coefficient (Dc) and Hausdorff distance (Hd). The proposed method was benchmarked against translation and rigid alignment based auto-segmentation. Results: For all organs, the auto-segmentation performed better than the baseline (translation) with an average processing time of 15 s per fraction CT. The overall improvements ranged from 2% (heart) to 32% (pancreas) in Dc, and 27% (heart) to 62% (spinal cord) in Hd. For liver, kidneys, gall bladder, stomach, spinal cord and heart, Dc above 0.85 was achieved. Duodenum and pancreas were the most challenging organs with both showing relatively larger spreads and medians of 0.79 and 2.1 mm for Dc and Hd, respectively. Conclusion: Based on the achieved accuracy and computational time we conclude that the investigated auto

  8. Social Stratification in Higher Education

    ERIC Educational Resources Information Center

    Grodsky, Eric; Jackson, Erika

    2009-01-01

    Background/Context: Over the past half century, scholars in a variety of fields have contributed to our understanding of the relationship between higher education and social stratification. We review this literature, highlighting complementarities and inconsistencies. Purpose/Objective/Research Question/Focus of Study: We situate our review of the…

  9. Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines

    PubMed Central

    Ansell, Stephen M.; Kyle, Robert A.; Reeder, Craig B.; Fonseca, Rafael; Mikhael, Joseph R.; Morice, William G.; Bergsagel, P. Leif; Buadi, Francis K.; Colgan, Joseph P.; Dingli, David; Dispenzieri, Angela; Greipp, Philip R.; Habermann, Thomas M.; Hayman, Suzanne R.; Inwards, David J.; Johnston, Patrick B.; Kumar, Shaji K.; Lacy, Martha Q.; Lust, John A.; Markovic, Svetomir N.; Micallef, Ivana N. M.; Nowakowski, Grzegorz S.; Porrata, Luis F.; Roy, Vivek; Russell, Stephen J.; Short, Kristen E. Detweiler; Stewart, A. Keith; Thompson, Carrie A.; Witzig, Thomas E.; Zeldenrust, Steven R.; Dalton, Robert J.; Rajkumar, S. Vincent; Gertz, Morie A.

    2010-01-01

    Waldenström macroglobulinemia is a B-cell malignancy with lymphoplasmacytic infiltration in the bone marrow or lymphatic tissue and a monoclonal immunoglobulin M protein (IgM) in the serum. It is incurable with current therapy, and the decision to treat patients as well as the choice of treatment can be complex. Using a risk-adapted approach, we provide recommendations on timing and choice of therapy. Patients with smoldering or asymptomatic Waldenström macroglobulinemia and preserved hematologic function should be observed without therapy. Symptomatic patients with modest hematologic compromise, IgM-related neuropathy that requires therapy, or hemolytic anemia unresponsive to corticosteroids should receive standard doses of rituximab alone without maintenance therapy. Patients who have severe constitutional symptoms, profound hematologic compromise, symptomatic bulky disease, or hyperviscosity should be treated with the DRC (dexamethasone, rituximab, cyclophosphamide) regimen. Any patient with symptoms of hyperviscosity should first be treated with plasmapheresis. For patients who experience relapse after a response to initial therapy of more than 2 years' duration, the original therapy should be repeated. For patients who had an inadequate response to initial therapy or a response of less than 2 years' duration, an alternative agent or combination should be used. Autologous stem cell transplant should be considered in all eligible patients with relapsed disease. PMID:20702770

  10. Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project

    PubMed Central

    Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S

    2015-01-01

    Introduction Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. Methods and analysis The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three ‘all-comer’ studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. Ethics and dissemination The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and

  11. Pre-admission NT-proBNP improves diagnostic yield and risk stratification – the NT-proBNP for EValuation of dyspnoeic patients in the Emergency Room and hospital (BNP4EVER) study

    PubMed Central

    Januzzi, James L; Medvedovski, Margarita; Sharist, Moshe; Shochat, Michael; Ashkar, Jalal; Peschansky, Pavel; Haim, Shmuel Bar; Blondheim, David S; Glikson, Michael; Shotan, Avraham

    2012-01-01

    Background: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) level is useful to diagnose or exclude acutely decompensated heart failure (ADHF) in dyspnoeic patients presenting to the emergency department (ED). Aim: To evaluate the impact of ED NT-proBNP testing on admission, length of stay (LOS), discharge diagnosis and long-term outcome. Methods: Dyspnoeic patients were randomized in the ED to NT-proBNP testing. Admission and discharge diagnoses, and outcomes were examined. Results: During 17 months, 470 patients were enrolled and followed for 2.0±1.3 years. ADHF likelihood, determined at study conclusion by validated criteria, established ADHF diagnosis as unlikely in 86 (17%), possible in 120 (24%), and likely in 293 (59%) patients. The respective admission rates in these subgroups were 80, 91, and 96%, regardless of blinding, and 61.9% of blinded vs. 74.5% of unblinded ADHF-likely patients were correctly diagnosed at discharge (p=0.029), with similar LOS. 2-year mortality within subgroups was unaffected by test, but was lower in ADHF-likely patients with NT-proBNP levels below median (5000 pg/ml) compared with those above median (p=0.002). Incidence of recurrent cardiac events tracked NT-proBNP levels. Conclusion: ED NT-proBNP testing did not affect admission, LOS, 2-year survival, or recurrent cardiac events among study patients but improved diagnosis at discharge, and allowed risk stratification even within the ADHF-likely group. (ClinicalTrials.gov#NCT00271128) PMID:24062895

  12. Cancer Stratification by Molecular Imaging

    PubMed Central

    Weber, Justus; Haberkorn, Uwe; Mier, Walter

    2015-01-01

    The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2). Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter), as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers. PMID:25749472

  13. Principal stratification in causal inference.

    PubMed

    Frangakis, Constantine E; Rubin, Donald B

    2002-03-01

    Many scientific problems require that treatment comparisons be adjusted for posttreatment variables, but the estimands underlying standard methods are not causal effects. To address this deficiency, we propose a general framework for comparing treatments adjusting for posttreatment variables that yields principal effects based on principal stratification. Principal stratification with respect to a posttreatment variable is a cross-classification of subjects defined by the joint potential values of that posttreatment variable tinder each of the treatments being compared. Principal effects are causal effects within a principal stratum. The key property of principal strata is that they are not affected by treatment assignment and therefore can be used just as any pretreatment covariate. such as age category. As a result, the central property of our principal effects is that they are always causal effects and do not suffer from the complications of standard posttreatment-adjusted estimands. We discuss briefly that such principal causal effects are the link between three recent applications with adjustment for posttreatment variables: (i) treatment noncompliance, (ii) missing outcomes (dropout) following treatment noncompliance. and (iii) censoring by death. We then attack the problem of surrogate or biomarker endpoints, where we show, using principal causal effects, that all current definitions of surrogacy, even when perfectly true, do not generally have the desired interpretation as causal effects of treatment on outcome. We go on to forrmulate estimands based on principal stratification and principal causal effects and show their superiority. PMID:11890317

  14. Lipoprotein-Associated Phospholipase A2 and High-Sensitivity C-Reactive Protein Improve the Stratification of Ischemic Stroke Risk in the Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Nambi, Vijay; Hoogeveen, Ron C.; Chambless, Lloyd; Hu, Yijuan; Bang, Heejung; Coresh, Josef; Ni, Hanyu; Boerwinkle, Eric; Mosley, Thomas; Sharrett, Richey; Folsom, Aaron R.; Ballantyne, Christie M.

    2009-01-01

    Background and Purpose Inflammation plays a critical role in the development of vascular disease, and increased levels of the inflammatory biomarkers, lipoprotein-associated phospholipase A2 (Lp-PLA2), and high-sensitivity C-reactive protein (hs-CRP) have been shown to be associated with an increased risk for ischemic stroke. Methods In a prospective case– cohort (n=949) study in 12 762 apparently healthy, middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study, we first examined whether Lp-PLA2 and hs-CRP levels improved the area under the receiver operator characteristic curve (AUC) for 5-year ischemic stroke risk. We then examined how Lp-PLA2 and hs-CRP levels altered classification of individuals into low-, intermediate-, or high-risk categories compared with traditional risk factors. Results In a model using traditional risk factors alone, the AUC adjusted for optimism was 0.732, whereas adding hs-CRP improved the AUC to 0.743, and adding Lp-PLA2 significantly improved the AUC to 0.752. Addition of hs-CRP and Lp-PLA2 together in the model improved the AUC to 0.761, and the addition of the interaction between Lp-PLA2 and hs-CRP further significantly improved the AUC to 0.774. With the use of traditional risk factors to assess 5-year risk for ischemic stroke, 86% of participants were categorized as low risk (<2%); 11%, intermediate risk (2% to 5%); and 3%, high risk (>5%). The addition of hs-CRP, Lp-PLA2, and their interaction to the model reclassified 4%, 39%, and 34% of the low-, intermediate- and high-risk categories, respectively. Conclusion Lp-PLA2 and hs-CRP may be useful in individuals classified as intermediate risk for ischemic stroke by traditional risk factors. PMID:19095974

  15. A canopy-related stratification of a Southern pine forest using Landsat digital data

    NASA Technical Reports Server (NTRS)

    Williams, D. L.

    1976-01-01

    An investigation was undertaken to determine if a consistent stratification of a Southern pine forest could be obtained by using Landsat multispectral scanner data to assess crown closure. Winter and summer Landsat scenes of the North Carolina coastal region were analyzed individually and then registered and merged to take advantage of temporal changes in the forest canopy. Three levels of pine crown closure were accurately delineated. The applicability of this stratification as supplemental input to a forest inventory system is also discussed.

  16. A canopy-related stratification of a southern pine forest using LANDSAT digital data

    NASA Technical Reports Server (NTRS)

    Williams, D. L.

    1976-01-01

    An investigation was undertaken to determine if a consistent stratification of a Southern pine forest could be obtained by using LANDSAT multispectral scanner data to assess crown closure. Winter and summer LANDSAT scenes of the North Carolina coastal region were analyzed individually and then registered and merged to take advantage of temporal changes in the forest canopy. Three levels of pine crown closure were accurately delineated. The applicability of this stratification as supplemental input to a forest inventory system is also discussed.

  17. Chemical stratification of the mantle

    NASA Technical Reports Server (NTRS)

    Anderson, D. L.

    1979-01-01

    A possible scenario for the chemical stratification of the earth's mantle is presented. Differentiation of the mantle by either the production of basaltic magmas or partial melting by the upper mantle is proposed to lead to a thick basalt layer, the lower part of which is converted to eclogite as the earth cools. Density estimates indicate that the eclogite formed would not be able to sink to below 670 km. The eclogite layer is thus demonstrated to be trapped as a result of whole-mantle convection and possible irreversible differentiation of the mantle into eclogite and overlying residual peridotite layers.

  18. Predicting the risk of sudden cardiac death.

    PubMed

    Lerma, Claudia; Glass, Leon

    2016-05-01

    Sudden cardiac death (SCD) is the result of a change of cardiac activity from normal (typically sinus) rhythm to a rhythm that does not pump adequate blood to the brain. The most common rhythms leading to SCD are ventricular tachycardia (VT) or ventricular fibrillation (VF). These result from an accelerated ventricular pacemaker or ventricular reentrant waves. Despite significant efforts to develop accurate predictors for the risk of SCD, current methods for risk stratification still need to be improved. In this article we briefly review current approaches to risk stratification. Then we discuss the mathematical basis for dynamical transitions (called bifurcations) that may lead to VT and VF. One mechanism for transition to VT or VF involves a perturbation by a premature ventricular complex (PVC) during sinus rhythm. We describe the main mechanisms of PVCs (reentry, independent pacemakers and abnormal depolarizations). An emerging approach to risk stratification for SCD involves the development of individualized dynamical models of a patient based on measured anatomy and physiology. Careful analysis and modelling of dynamics of ventricular arrhythmia on an individual basis will be essential in order to improve risk stratification for SCD and to lay a foundation for personalized (precision) medicine in cardiology. PMID:26660287

  19. Stable density stratification solar pond

    NASA Technical Reports Server (NTRS)

    Lansing, F. L. (Inventor)

    1985-01-01

    A stable density-stratification solar pond for use in the collection and storage of solar thermal energy including a container having a first section characterized by an internal wall of a substantially cylindrical configuration and a second section having an internal wall of a substantially truncated conical configuration surmounting the first section in coaxial alignment therewith, the second section of said container being characterized by a base of a diameter substantially equal to the diameter of the first section and a truncated apex defining a solar energy acceptance opening is discussed. A body of immiscible liquids is disposed within the container and comprises a lower portion substantially filling the first section of the container and an upper portion substantially filling the second section of the container, said lower portion being an aqueous based liquid of a darker color than the upper portion and of a greater density. A protective cover plate is removably provided for covering the acceptance opening.

  20. Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases

    PubMed Central

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Lin, Xiaoling; Helfand, Brian T; Brendler, Charles B; Conran, Carly; Gong, Jian; Wu, Yishuo; Gao, Xu; Chen, Yaqing; Zheng, S Lilly; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

    2016-01-01

    Genetic risk score (GRS) based on disease risk-associated single nucleotide polymorphisms (SNPs) is an informative tool that can be used to provide inherited information for specific diseases in addition to family history. However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specific GRS for predicting prostate cancer (PCa) among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians (GRS7), and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group (GRS76). The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve (AUC) than GRS76 for discriminating PCa (0.602 vs 0.573) and high-grade PCa (0.603 vs 0.575) but did not reach statistical significance. GRS7 had a better (up to 13% at different cutoffs) positive predictive value (PPV) than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians. PMID:27140652

  1. Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases.

    PubMed

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Lin, Xiaoling; Helfand, Brian T; Brendler, Charles B; Conran, Carly; Gong, Jian; Wu, Yishuo; Gao, Xu; Chen, Yaqing; Zheng, S Lilly; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

    2016-01-01

    Genetic risk score (GRS) based on disease risk-associated single nucleotide polymorphisms (SNPs) is an informative tool that can be used to provide inherited information for specific diseases in addition to family history. However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specific GRS for predicting prostate cancer (PCa) among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians (GRS7), and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group (GRS76). The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve (AUC) than GRS76 for discriminating PCa (0.602 vs 0.573) and high-grade PCa (0.603 vs 0.575) but did not reach statistical significance. GRS7 had a better (up to 13% at different cutoffs) positive predictive value (PPV) than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians. PMID:27140652

  2. Non-coding RNAs Enabling Prognostic Stratification and Prediction of Therapeutic Response in Colorectal Cancer Patients.

    PubMed

    Perakis, Samantha O; Thomas, Joseph E; Pichler, Martin

    2016-01-01

    Colorectal cancer (CRC) is a heterogeneous disease and current treatment options for patients are associated with a wide range of outcomes and tumor responses. Although the traditional TNM staging system continues to serve as a crucial tool for estimating CRC prognosis and for stratification of treatment choices and long-term survival, it remains limited as it relies on macroscopic features and cases of surgical resection, fails to incorporate new molecular data and information, and cannot perfectly predict the variety of outcomes and responses to treatment associated with tumors of the same stage. Although additional histopathologic features have recently been applied in order to better classify individual tumors, the future might incorporate the use of novel molecular and genetic markers in order to maximize therapeutic outcome and to provide accurate prognosis. Such novel biomarkers, in addition to individual patient tumor phenotyping and other validated genetic markers, could facilitate the prediction of risk of progression in CRC patients and help assess overall survival. Recent findings point to the emerging role of non-protein-coding regions of the genome in their contribution to the progression of cancer and tumor formation. Two major subclasses of non-coding RNAs (ncRNAs), microRNAs and long non-coding RNAs, are often dysregulated in CRC and have demonstrated their diagnostic and prognostic potential as biomarkers. These ncRNAs are promising molecular classifiers and could assist in the stratification of patients into appropriate risk groups to guide therapeutic decisions and their expression patterns could help determine prognosis and predict therapeutic options in CRC. PMID:27573901

  3. Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score

    PubMed Central

    Cavalcanti, Paulo Ernando Ferraz; Sá, Michel Pompeu Barros de Oliveira; dos Santos, Cecília Andrade; Esmeraldo, Isaac Melo; Chaves, Mariana Leal; Lins, Ricardo Felipe de Albuquerque; Lima, Ricardo de Carvalho

    2015-01-01

    Objective To determine whether stratification of complexity models in congenital heart surgery (RACHS-1, Aristotle basic score and STS-EACTS mortality score) fit to our center and determine the best method of discriminating hospital mortality. Methods Surgical procedures in congenital heart diseases in patients under 18 years of age were allocated to the categories proposed by the stratification of complexity methods currently available. The outcome hospital mortality was calculated for each category from the three models. Statistical analysis was performed to verify whether the categories presented different mortalities. The discriminatory ability of the models was determined by calculating the area under the ROC curve and a comparison between the curves of the three models was performed. Results 360 patients were allocated according to the three methods. There was a statistically significant difference between the mortality categories: RACHS-1 (1) - 1.3%, (2) - 11.4%, (3)-27.3%, (4) - 50 %, (P<0.001); Aristotle basic score (1) - 1.1%, (2) - 12.2%, (3) - 34%, (4) - 64.7%, (P<0.001); and STS-EACTS mortality score (1) - 5.5 %, (2) - 13.6%, (3) - 18.7%, (4) - 35.8%, (P<0.001). The three models had similar accuracy by calculating the area under the ROC curve: RACHS-1- 0.738; STS-EACTS-0.739; Aristotle- 0.766. Conclusion The three models of stratification of complexity currently available in the literature are useful with different mortalities between the proposed categories with similar discriminatory capacity for hospital mortality. PMID:26107445

  4. Mediation analysis with principal stratification.

    PubMed

    Gallop, Robert; Small, Dylan S; Lin, Julia Y; Elliott, Michael R; Joffe, Marshall; Ten Have, Thomas R

    2009-03-30

    In assessing the mechanism of treatment efficacy in randomized clinical trials, investigators often perform mediation analyses by analyzing if the significant intent-to-treat treatment effect on outcome occurs through or around a third intermediate or mediating variable: indirect and direct effects, respectively. Standard mediation analyses assume sequential ignorability, i.e. conditional on covariates the intermediate or mediating factor is randomly assigned, as is the treatment in a randomized clinical trial. This research focuses on the application of the principal stratification (PS) approach for estimating the direct effect of a randomized treatment but without the standard sequential ignorability assumption. This approach is used to estimate the direct effect of treatment as a difference between expectations of potential outcomes within latent subgroups of participants for whom the intermediate variable behavior would be constant, regardless of the randomized treatment assignment. Using a Bayesian estimation procedure, we also assess the sensitivity of results based on the PS approach to heterogeneity of the variances among these principal strata. We assess this approach with simulations and apply it to two psychiatric examples. Both examples and the simulations indicated robustness of our findings to the homogeneous variance assumption. However, simulations showed that the magnitude of treatment effects derived under the PS approach were sensitive to model mis-specification. PMID:19184975

  5. Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary Calcium Scoring, and C-Reactive Protein, and a Global Treat-All Strategy: A Comparative--Effectiveness Modeling Study

    PubMed Central

    Galper, Benjamin Z.; Wang, Y. Claire; Einstein, Andrew J.

    2015-01-01

    Background Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown. Methods We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe. Results Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over $238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event. Conclusions Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the

  6. Accurate and Robust Genomic Prediction of Celiac Disease Using Statistical Learning

    PubMed Central

    Abraham, Gad; Tye-Din, Jason A.; Bhalala, Oneil G.; Kowalczyk, Adam; Zobel, Justin; Inouye, Michael

    2014-01-01

    Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87–0.89) and in independent replication across cohorts (AUC of 0.86–0.9), despite differences in ethnicity. The models explained 30–35% of disease variance and up to ∼43% of heritability. The GRS's utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases. PMID:24550740

  7. “Any Condomless Anal Intercourse” is No Longer an Accurate Measure of HIV Sexual risk Behavior in Gay and Other Men Who have Sex with Men

    PubMed Central

    Jin, Fengyi; Prestage, Garrett P.; Mao, Limin; Poynten, I. Mary; Templeton, David J.; Grulich, Andrew E.; Zablotska, Iryna

    2015-01-01

    Background: Condomless anal intercourse (CLAI) has long been recognized as the primary mode of sexual transmission of HIV in gay and other men who have sex with men (MSM). A variety of measures of CLAI have been commonly used in behavioral surveillance for HIV risk and to forecast trends in HIV infection. However, gay and other MSM’s sexual practices changed as the understanding of disease and treatment options advance. In the present paper, we argue that summary measures such as “any CLAI” do not accurately measure HIV sexual risk behavior. Methods: Participants were 1,427 HIV-negative men from the Health in Men cohort study run from 2001 to 2007 in Sydney, Australia, with six-monthly interviews. At each interview, detailed quantitative data on the number of episodes of insertive and receptive CLAI in the last 6 months were collected, separated by partner type (regular vs. casual) and partners’ HIV status (negative, positive, and HIV status unknown). Results: A total of 228,064 episodes of CLAI were reported during the study period with a mean of 44 episodes per year per participant (median: 14). The great majority of CLAI episodes were with a regular partner (92.6%), most of them with HIV-negative regular partners (84.8%). Participants were more likely to engage in insertive CLAI with casual than with regular partners (66.7 vs. 55.3% of all acts of CLAI with each partner type, p < 0.001). Men were more likely to report CLAI in the receptive position with HIV-negative and HIV status unknown partners than with HIV-positive partners (p < 0.001 for both regular and casual partners). Conclusion: Gay and other MSM engaging in CLAI demonstrate clear patterns of HIV risk reduction behavior. As HIV prevention enters the era of antiretroviral-based biomedical approach, using all forms of CLAI indiscriminately as a measure of HIV behavioral risk is not helpful in understanding the current drivers of HIV transmission in the community. PMID:25774158

  8. Bathymetry, stratification, and internal seiche structure

    NASA Astrophysics Data System (ADS)

    Fricker, P. D.; Nepf, H. M.

    2000-06-01

    Internal seiches play a significant role in a broad range of physical, chemical, and biological processes in lakes. A detailed assessment of the impact of seiching requires an understanding of seiche structure, which is determined by bathymetry and stratification. In this study, internal seiche solutions are evaluated for arbitrary bathymetry and continuous stratification using a two-dimensional numerical model. Formulated in terms of a stream function, the model produces a finite set of linear internal wave eigenmodes and allows the computation of the complete velocity field (over a grid) associated with each seiche mode. Several idealized configurations of continuous stratification and variable bathymetry are used to explore the effect of nonuniform systems on internal wave structure. In particular, we focus on bed velocity distribution and the resulting potential impact on scalar fluxes, sediment transport, and internal wave damping. Model results are also compared to thermistor chain data collected in the Upper Mystic Lake (UML, Winchester, Massachusetts). Using an idealized description of the UML bathymetry and density profiles which emulate the seasonal variation of stratification in the lake, the evolution of bed velocities during the autumnal breakdown in stratification is assessed, providing insight into the fate of the contaminants entering the lake.

  9. Experimental Analysis of Thermal Stratification in a Heat Storage Tank Using Stratification Pipe

    NASA Astrophysics Data System (ADS)

    Boloņina, A.; Rochas, C.; Blumberga, D.

    2009-01-01

    The heat storage tank is an important element in any heating system where the heat source is not able to provide heat accordingly to consumer demand (for example solar collector systems, solid fuel boilers etc). Better heat storage efficiency can be achieved by providing good thermal stratification in the heat storage tanks. One of the best methods of increasing the degree of thermal stratification is the stratification pipes. In the Environmental monitoring laboratory of the Institute of Energy Systems and Environment (Riga Technical University, an experimental heat storage system has been developed and used for testing and studying stratification devices under different thermodynamic and hydraulic conditions. The experimental study carried out on the efficiency of the stratification pipe produced by German company SOLVIS Solar Systeme GmbH under different flow parameters, has been analyzed. The main aim of the experimental study was to define optimal heating system operation parameters to achieve good performance of the stratification pipe and a high degree of thermal stratification in the heat storage tank.

  10. Can the American College of Surgeons Risk Calculator Predict 30-Day Complications After Knee and Hip Arthroplasty?

    PubMed

    Edelstein, Adam I; Kwasny, Mary J; Suleiman, Linda I; Khakhkhar, Rishi H; Moore, Michael A; Beal, Matthew D; Manning, David W

    2015-09-01

    Accurate risk stratification of patients undergoing total hip (THA) and knee (TKA) arthroplasty is essential in the highly scrutinized world of pay-for-performance, value-driven healthcare. We assessed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator's ability to predict 30-day complications using 1066 publicly-reported Medicare patients undergoing primary THA or TKA. Risk estimates were significantly associated with complications in the categories of any complication (P = .005), cardiac complication (P < .001), pneumonia (P < .001) and discharge to skilled nursing facility (P < .001). However, predictability of complication occurrence was poor for all complications assessed. To facilitate the equitable provision and reimbursement of patient care, further research is needed to develop accurate risk stratification tools in TKA and THA surgery. PMID:26165953

  11. Effect of sample stratification on dairy GWAS results

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Artificial insemination and genetic selection are major factors contributing to population stratification in dairy cattle. In this study, we analyzed the effect of sample stratification and the effect of stratification correction on results of a dairy genome-wide association study (GWAS)....

  12. A Comparative Review of Stratification Texts and Readers

    ERIC Educational Resources Information Center

    Peoples, Clayton D.

    2012-01-01

    Social stratification is a core substantive area within sociology. There are a number of textbooks and readers available on the market that deal with this central topic. In this article, I conduct a comparative review of (a) four stratification textbooks and (b) four stratification readers. (Contains 2 tables.)

  13. Risk stratification and stroke prevention therapy care gaps in Canadian atrial fibrillation patients (from the Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation chart audit).

    PubMed

    Patel, Ashish D; Tan, Mary K; Angaran, Paul; Bell, Alan D; Berall, Murray; Bucci, Claudia; Demchuk, Andrew M; Essebag, Vidal; Goldin, Lianne; Green, Martin S; Gregoire, Jean C; Gross, Peter L; Heilbron, Brett; Lin, Peter J; Ramanathan, Krishnan; Skanes, Allan; Wheeler, Bruce H; Goodman, Shaun G

    2015-03-01

    The objectives of this national chart audit (January to June 2013) of 6,346 patients with atrial fibrillation (AF; ≥18 years without a significant heart valve disorder) from 647 primary care physicians were to (1) describe the frequency of stroke and bleed risk assessments in patients with nonvalvular AF by primary care physicians, including the accuracy of these assessments relative to established predictive indexes; (2) outline contemporary methods of anticoagulation used; and (3) report the time in the therapeutic range among patients prescribed warfarin. An annual stroke risk assessment was not undertaken in 15% and estimated without a formal risk tool in 33%; agreement with CHADS2 score estimation was seen in 87% of patients. Major bleeding risk assessment was not undertaken in 25% and estimated without a formal risk tool in 47%; agreement with HAS-BLED score estimation was observed in 64% with physician overestimation in 26% of patients. Antithrombotic therapy included warfarin (58%), dabigatran (22%), rivaroxaban (14%), and apixaban (<1%). Among warfarin-treated patients, the median international normalized ratio was 2.4 and time in therapeutic range (TTR) was 73%; however, the TTR was <50% in 845 (25%), 50% to 69% in 674 (20%), and ≥70% in 1,827 (55%) patients. In conclusion, we describe a contemporary real-world elderly population with AF at important risk for stroke. There is apparent overestimation of bleeding risk in many patients. Warfarin was the dominant stroke prevention treatment; however, the suggested TTR target was achieved in only 55% of these patients. PMID:25727083

  14. Drainage and Stratification Kinetics of Foam Films

    NASA Astrophysics Data System (ADS)

    Zhang, Yiran; Sharma, Vivek

    2014-03-01

    Baking bread, brewing cappuccino, pouring beer, washing dishes, shaving, shampooing, whipping eggs and blowing bubbles all involve creation of aqueous foam films. Foam lifetime, drainage kinetics and stability are strongly influenced by surfactant type (ionic vs non-ionic), and added proteins, particles or polymers modify typical responses. The rate at which fluid drains out from a foam film, i.e. drainage kinetics, is determined in the last stages primarily by molecular interactions and capillarity. Interestingly, for certain low molecular weight surfactants, colloids and polyelectrolyte-surfactant mixtures, a layered ordering of molecules, micelles or particles inside the foam films leads to a stepwise thinning phenomena called stratification. Though stratification is observed in many confined systems including foam films containing particles or polyelectrolytes, films containing globular proteins seem not to show this behavior. Using a Scheludko-type cell, we experimentally study the drainage and stratification kinetics of horizontal foam films formed by protein-surfactant mixtures, and carefully determine how the presence of proteins influences the hydrodynamics and thermodynamics of foam films.

  15. Temperature Stratification in a Cryogenic Fuel Tank

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew John; Smelyanskiy, Vadim; Boschee, Jacob; Foygel, Michael Gregory

    2013-01-01

    A reduced dynamical model describing temperature stratification effects driven by natural convection in a liquid hydrogen cryogenic fuel tank has been developed. It accounts for cryogenic propellant loading, storage, and unloading in the conditions of normal, increased, and micro- gravity. The model involves multiple horizontal control volumes in both liquid and ullage spaces. Temperature and velocity boundary layers at the tank walls are taken into account by using correlation relations. Heat exchange involving the tank wall is considered by means of the lumped-parameter method. By employing basic conservation laws, the model takes into consideration the major multi-phase mass and energy exchange processes involved, such as condensation-evaporation of the hydrogen, as well as flows of hydrogen liquid and vapor in the presence of pressurizing helium gas. The model involves a liquid hydrogen feed line and a tank ullage vent valve for pressure control. The temperature stratification effects are investigated, including in the presence of vent valve oscillations. A simulation of temperature stratification effects in a generic cryogenic tank has been implemented in Matlab and results are presented for various tank conditions.

  16. Chemical stratification in the silicate earth

    NASA Technical Reports Server (NTRS)

    Herzberg, C. T.

    1983-01-01

    A primary stratigraphic model is presented for the distribution of depleted, enriched, and primordial isotopic mantle components that have been formed by the transport of magmas at the begining of geological history. Depleted midoceanic ridge basalt source regions were established in the uppermost part of the upper mantle, while the primordial mantle was located at the middle and deepest regions of an upper mantle which was processed by anhydrous melting and crystallization. The lower mantle became heterogeneous, with enrichments at the top and depletions elsewhere. It is suggested that the present day isotopic structure of the mantle has inherited elements of this primary stratification.

  17. Simulation of Thermal Stratification in BWR Suppression Pools with One Dimensional Modeling Method

    SciTech Connect

    Haihua Zhao; Ling Zou; Hongbin Zhang

    2014-01-01

    The suppression pool in a boiling water reactor (BWR) plant not only is the major heat sink within the containment system, but also provides the major emergency cooling water for the reactor core. In several accident scenarios, such as a loss-of-coolant accident and extended station blackout, thermal stratification tends to form in the pool after the initial rapid venting stage. Accurately predicting the pool stratification phenomenon is important because it affects the peak containment pressure; the pool temperature distribution also affects the NPSHa (available net positive suction head) and therefore the performance of the Emergency Core Cooling System and Reactor Core Isolation Cooling System pumps that draw cooling water back to the core. Current safety analysis codes use zero dimensional (0-D) lumped parameter models to calculate the energy and mass balance in the pool; therefore, they have large uncertainties in the prediction of scenarios in which stratification and mixing are important. While three-dimensional (3-D) computational fluid dynamics (CFD) methods can be used to analyze realistic 3-D configurations, these methods normally require very fine grid resolution to resolve thin substructures such as jets and wall boundaries, resulting in a long simulation time. For mixing in stably stratified large enclosures, the BMIX++ code (Berkeley mechanistic MIXing code in C++) has been developed to implement a highly efficient analysis method for stratification where the ambient fluid volume is represented by one-dimensional (1-D) transient partial differential equations and substructures (such as free or wall jets) are modeled with 1-D integral models. This allows very large reductions in computational effort compared to multi-dimensional CFD modeling. One heat-up experiment performed at the Finland POOLEX facility, which was designed to study phenomena relevant to Nordic design BWR suppression pool including thermal stratification and mixing, is used for

  18. An efficient modeling method for thermal stratification simulation in a BWR suppression pool

    SciTech Connect

    Haihua Zhao; Ling Zou; Hongbin Zhang; Hua Li; Walter Villanueva; Pavel Kudinov

    2012-09-01

    The suppression pool in a BWR plant not only is the major heat sink within the containment system, but also provides major emergency cooling water for the reactor core. In several accident scenarios, such as LOCA and extended station blackout, thermal stratification tends to form in the pool after the initial rapid venting stage. Accurately predicting the pool stratification phenomenon is important because it affects the peak containment pressure; and the pool temperature distribution also affects the NPSHa (Available Net Positive Suction Head) and therefore the performance of the pump which draws cooling water back to the core. Current safety analysis codes use 0-D lumped parameter methods to calculate the energy and mass balance in the pool and therefore have large uncertainty in prediction of scenarios in which stratification and mixing are important. While 3-D CFD methods can be used to analyze realistic 3D configurations, these methods normally require very fine grid resolution to resolve thin substructures such as jets and wall boundaries, therefore long simulation time. For mixing in stably stratified large enclosures, the BMIX++ code has been developed to implement a highly efficient analysis method for stratification where the ambient fluid volume is represented by 1-D transient partial differential equations and substructures such as free or wall jets are modeled with 1-D integral models. This allows very large reductions in computational effort compared to 3-D CFD modeling. The POOLEX experiments at Finland, which was designed to study phenomena relevant to Nordic design BWR suppression pool including thermal stratification and mixing, are used for validation. GOTHIC lumped parameter models are used to obtain boundary conditions for BMIX++ code and CFD simulations. Comparison between the BMIX++, GOTHIC, and CFD calculations against the POOLEX experimental data is discussed in detail.

  19. Inertial destabilization of highly viscous microfluidic stratifications

    NASA Astrophysics Data System (ADS)

    Hu, Xiaoyi; Cubaud, Thomas

    2016-08-01

    The hydrodynamic stability of stratifications made between miscible fluids having large differences in viscosity is experimentally investigated in square microchannels. Parallel fluid layers with a fast central stream and a slow sheath flow are produced by focusing a low-viscosity fluid into a high-viscosity fluid in a straight microchannel. Three regimes are identified and include diffusive, stable, and unstable flow patterns. In the unstable regime, coupled interfacial waves are seen to significantly disrupt strata when the Reynolds number associated with the low-viscosity stream is above 90. Several functional relationships are developed for the stratification width, propagating celerity, wavelength, amplitude, and frequency of interfacial waves over a range of viscosities and flow rates. We demonstrate, in particular, the wave phase locking for small central streams and show the production of high-viscosity fluid ligaments at the wave crests. In this case, a minute amount of high-viscosity fluid is entrained and blended into the low-viscosity fluid stream, thereby providing an original in-line mixing method for continuously adding a viscosifier to a thin fluid in microchannels.

  20. N-terminal pro B type natriuretic peptide in high cardiovascular-risk patients for noncardiac surgery: What is the current prognostic evidence?

    PubMed Central

    Malhotra, Anita K.; Ramakrishna, Harish

    2016-01-01

    As millions of surgical procedures are performed worldwide on an aging population with multiple comorbidities, accurate and simple perioperative risk stratification is critical. The cardiac biomarker, brain natriuretic peptide (BNP), has generated considerable interest as it is easy to obtain and appears to have powerful predictive and prognostic capabilities. BNP is currently being used to guide medical therapy for heart failure and has been added to several algorithms for perioperative risk stratification. This review examines the current evidence for the use of BNP in the perioperative period in patients who are at high-cardiovascular risk for noncardiac surgery. In addition, we examined the use of BNP in patients with pulmonary embolism and left ventricular assist devices. The available data strongly suggest that the addition of BNP to perioperative risk calculators is beneficial; however, whether this determination of risk will impact outcomes, remains to be seen. PMID:27052075

  1. Influence of upper-ocean stratification on tropical cyclone-induced surface cooling in the Bay of Bengal

    NASA Astrophysics Data System (ADS)

    Neetu, S.; Lengaigne, Matthieu; Vincent, Emmanuel M.; Vialard, JéRôMe; Madec, Gurvan; Samson, Guillaume; Ramesh Kumar, M. R.; Durand, Fabien

    2012-12-01

    Surface cooling induced by tropical cyclones (TCs) is about three times larger during premonsoon than during postmonsoon season in the Bay of Bengal. We investigate processes responsible for this seasonal contrast using an ocean general circulation model. The model is forced by TC winds prescribed from an analytic vortex using observed TC tracks and intensities during 1978-2007. The simulation accurately captures the seasonal cycle of salinity, temperature, and barrier layer in this region, with fresher waters, deeper upper-ocean stratification, and thicker barrier layers during postmonsoon season. It also reproduces the three times larger TC-induced cooling during premonsoon than during postmonsoon season. This difference is essentially related to seasonal changes in oceanic stratification rather than to differences in TC wind energy input. During the postmonsoon season, a deeper thermal stratification combined with a considerable upper-ocean freshening strongly inhibits surface cooling induced by vertical mixing underneath TCs. On average, thermal stratification accounts for ˜60% of this cooling reduction during postmonsoon season, while haline stratification accounts for the remaining 40%. Their respective contributions however strongly vary within the Bay: haline stratification explains a large part of the TC-induced cooling inhibition offshore of northern rim of the Bay (Bangladesh-Myanmar-east coast of India), where salinity seasonal changes are the strongest, while thermal stratification explains all the cooling inhibition in the southwestern Bay. This study hence advocates for an improved representation of upper-ocean salinity and temperature effects in statistical and dynamical TCs forecasts that could lead to significant improvements of TC intensity prediction skill.

  2. Assessment of PaO2/FiO2 for stratification of patients with moderate and severe acute respiratory distress syndrome

    PubMed Central

    Villar, Jesús; Blanco, Jesús; del Campo, Rafael; Andaluz-Ojeda, David; Díaz-Domínguez, Francisco J; Muriel, Arturo; Córcoles, Virgilio; Suárez-Sipmann, Fernando; Tarancón, Concepción; González-Higueras, Elena; López, Julia; Blanch, Lluis; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M

    2015-01-01

    Objectives A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at ARDS onset. Since the proposal did not mandate PaO2/FiO2 calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiO2 would not provide accurate assessment of lung injury severity. Design A prospective, multicentre, observational study. Setting A network of teaching hospitals. Participants 478 patients with eligible criteria for moderate (100300). Primary and secondary outcomes Group severity and hospital mortality. Results At ARDS onset, 173 patients had a PaO2/FiO2≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO2/FiO2 category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO2/FiO2 and non-standardised PaO2/FiO2 at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). Conclusions Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the

  3. Derivation and validation of a simple, accurate and robust prediction rule for risk of mortality in patients with Clostridium difficile infection

    PubMed Central

    2013-01-01

    Background Clostridium difficile infection poses a significant healthcare burden. However, the derivation of a simple, evidence based prediction rule to assist patient management has not yet been described. This study aimed to identify such a prediction rule to stratify hospital inpatients according to risk of all-cause mortality, at initial diagnosis of infection. Method Univariate, multivariate and decision tree procedures were used to deduce a prediction rule from over 186 variables; retrospectively collated from clinical data for 213 patients. The resulting prediction rule was validated on independent data from a cohort of 158 patients described by Bhangu et al. (Colorectal Disease, 12(3):241-246, 2010). Results Serum albumin levels (g/L) (P = 0.001), respiratory rate (resps /min) (P = 0.002), C-reactive protein (mg/L) (P = 0.034) and white cell count (mcL) (P = 0.049) were predictors of all-cause mortality. Threshold levels of serum albumin ≤ 24.5 g/L, C- reactive protein >228 mg/L, respiratory rate >17 resps/min and white cell count >12 × 103 mcL were associated with an increased risk of all-cause mortality. A simple four variable prediction rule was devised based on these threshold levels and when tested on the initial data, yield an area under the curve score of 0.754 (P < 0.001) using receiver operating characteristics. The prediction rule was then evaluated using independent data, and yield an area under the curve score of 0.653 (P = 0.001). Conclusions Four easily measurable clinical variables can be used to assess the risk of mortality of patients with Clostridium difficile infection and remains robust with respect to independent data. PMID:23849267

  4. Use of dose-dependent absorption into target tissues to more accurately predict cancer risk at low oral doses of hexavalent chromium.

    PubMed

    Haney, J

    2015-02-01

    The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses. PMID:25445295

  5. Teaching Stratification: Stimulating Interest and Critical Thinking through Research Projects.

    ERIC Educational Resources Information Center

    Misra, Joya

    1997-01-01

    Proposes that one goal in teaching stratification is to illustrate how powerfully stratification shapes society. Discusses an effort to stimulate critical thinking through student research projects. Lists three goals: involve students in research; show how race, class, and gender impact everyday life; and clarify the importance of these issues to…

  6. Comments: Should Principal Stratification Be Used to Study Mediational Processes?

    ERIC Educational Resources Information Center

    VanderWeele, Tyler J.

    2012-01-01

    Principal stratification provides an approach to study the effect of an exposure on an outcome within strata defined by the effect of the exposure on some third, posttreatment, variable (Frangakis & Rubin, 2002). There has been more recent interest in using principal stratification to study the extent to which the effect of an exposure on an…

  7. Education and Social Stratification Processes in Comparative Perspective.

    ERIC Educational Resources Information Center

    Kerckhoff, Alan C.

    2001-01-01

    Discusses three characteristics of educational systems that have been used to explain social stratification processes: stratification, standardization, and vocational specificity. Describes how these characteristics affect the movement of students through school and into the labor force in France, Germany, Great Britain, and the United States.…

  8. Impact of stratification and climatic perturbations to stratification on baroclinic and barotropic tides

    NASA Astrophysics Data System (ADS)

    Arbic, B. K.; Wetzel, A.; Cerovecki, I.; Hendershott, M.; Karsten, R. H.; Molinari, J.; Mueller, M.

    2012-12-01

    Recently there has been a great deal of interest in ocean mixing, primarily because ocean mixing is thought to control the strength of the oceanic meridional overturning circulation. An important source of ocean mixing is breaking internal waves, and an important energy source for oceanic internal waves is the astronomical tide. The ocean climate process team discussed in this session aims to develop parameterizations of internal-wave driven mixing which are suitable for the altered climates of our anticipated future as well as for the present climate. For this reason it is of interest to ask how climatic changes in the oceanic stratification have altered and will alter the ocean tides. By solving the Sturm-Liouville vertical mode problem with a present-day profile of oceanic temperature and salinity as well as the same profile altered by the observed temperature changes occuring over the last 135 years (Roemmich et al. 2012), we find that the square of the phase speed of the first mode baroclinic mode internal tide has changed by about 5-6% over that time frame. We alter the g' and layer depths of a two-layer numerical model of the global barotropic and baroclinic tides such that the phase speed changes by this amount. We will show the changes taking place in the baroclinic tide as well as in the barotropic tide. The barotropic tide changes because the phase speed of the barotropic tide depends on stratification (Gill 1982); this in turn affects the resonance of barotropic tides. The results of the numerical simulations are compared to a two-layer analytical model of tides in a forced-damped closed basin, which also predicts a sensitivity of both barotropic and baroclinic tides to stratification and to climatic perturbations to the stratification. Finally, the numerical results are compared to tide gauge observations of secular changes in tides occurring over the last century or so.

  9. Development of thermal stratification and destratification scaling concepts. Volume 2: Stratification. [tanks (containers)/tables (data)

    NASA Technical Reports Server (NTRS)

    Lovrich, T. N.; Schwartz, S. H.

    1975-01-01

    Temperature and pressure data obtained from the saturated Freon 113 PCA closed-tank stratification tests are presented. The data presented in tabular form are the test conditions, sensible heat values, and Freon 113 PCA liquid and ullage (vapor) properties. Also included, are graphical representations of the liquid bulk temperature and pressure histories, and dimensionless liquid-ullage delta-temperature profiles. Modified Grashof numbers and Fourier number-history data are also presented graphically.

  10. Mortality and Risk Stratification of HIV Infected Individuals.

    PubMed

    Heltemes, Bradley R

    2015-01-01

    For the first decade and a half after the Human Immunodeficiency Virus (HIV) was first identified, the prognosis for most people infected with HIV was quite poor. Life insurance companies responded accordingly and insurance laboratories developed new means to test for the infection. However, it is now clear that people with HIV infection are living longer and that the majority of deaths occurring among those on treatment are now no longer due to AIDS-defining illnesses. This review examines the results of selected studies which analyzed mortality outcomes in those with HIV infection, the many factors which influence those outcomes, and the limitations in the data and in their applicability to an insurance population. PMID:27584921

  11. An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

    PubMed Central

    Onken, Michael D.; Worley, Lori A.; Tuscan, Meghan D.; Harbour, J. William

    2010-01-01

    Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance, earlier intervention for metastasis, and stratification for entry into clinical trials of adjuvant therapy. Here, we migrate the expression profile from a hybridization-based microarray platform to a robust, clinically practical, PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples, including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples, even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma, and it provides a proof of principle for the development of similar assays for other cancers. PMID:20413675

  12. A Systematic Review of Human Bat Rabies Virus Variant Cases: Evaluating Unprotected Physical Contact with Claws and Teeth in Support of Accurate Risk Assessments.

    PubMed

    Dato, Virginia M; Campagnolo, Enzo R; Long, Jonah; Rupprecht, Charles E

    2016-01-01

    In the United States and Canada, the most recent documented cases of rabies have been attributed to bat rabies viruses (RABV). We undertook this systematic review in an effort to summarize and enhance understanding of the risk of infection for individuals who have been potentially exposed to a suspect or confirmed rabid bat. United States rabies surveillance summaries documented a total of 41 human bat-rabies virus variant verified non-transplant cases between 1990 and 2015. All cases were fatal. Seven (17.1%) of 41 cases reported a bite from a bat. Ten (24.3%) cases had unprotected physical contact (UPC); these included seven cases that had a bat land or crawl on them (contact with claws) and one case that touched a bat's teeth. Seven (17.1%) cases had probable UPC. Insectivorous bat teeth are extremely sharp and highly efficient for predation upon arthropod prey. Bats also have sharp claws on the end of their thumbs and feet. One of the most common bat RABV variants has an ability to replicate in non-neural cells. Questioning individuals about unprotected contact with bat teeth and claws (including a bat landing or crawling on a person) may help identify additional exposures. PMID:27459720

  13. A Systematic Review of Human Bat Rabies Virus Variant Cases: Evaluating Unprotected Physical Contact with Claws and Teeth in Support of Accurate Risk Assessments

    PubMed Central

    Campagnolo, Enzo R.; Long, Jonah; Rupprecht, Charles E.

    2016-01-01

    In the United States and Canada, the most recent documented cases of rabies have been attributed to bat rabies viruses (RABV). We undertook this systematic review in an effort to summarize and enhance understanding of the risk of infection for individuals who have been potentially exposed to a suspect or confirmed rabid bat. United States rabies surveillance summaries documented a total of 41 human bat-rabies virus variant verified non-transplant cases between 1990 and 2015. All cases were fatal. Seven (17.1%) of 41 cases reported a bite from a bat. Ten (24.3%) cases had unprotected physical contact (UPC); these included seven cases that had a bat land or crawl on them (contact with claws) and one case that touched a bat’s teeth. Seven (17.1%) cases had probable UPC. Insectivorous bat teeth are extremely sharp and highly efficient for predation upon arthropod prey. Bats also have sharp claws on the end of their thumbs and feet. One of the most common bat RABV variants has an ability to replicate in non-neural cells. Questioning individuals about unprotected contact with bat teeth and claws (including a bat landing or crawling on a person) may help identify additional exposures. PMID:27459720

  14. Causes and consequences of outer core stratification

    NASA Astrophysics Data System (ADS)

    Helffrich, George; Kaneshima, Satoshi

    2013-10-01

    The Earth’s outer core appears to be compositionally layered. Exotic mechanisms such as an original chemically layered core preserved from the Earth’s accretionary period, or compositionally different core material delivered by a Moon-creating impactor are conceivable, but require a core whose outermost part has been stratified throughout core history, relying on unknowable processes to achieve. Barodiffusion and core-mantle reaction lead to layers significantly thinner than observed. We show that a balance of mass transferred from the inner core to the top of the outer core is possible, and that the stratification could arise as a byproduct of light element accumulation. However, if a subadiabatic thermal gradient at the top of the outer core exists that quells radial flow, it could serve as a witness of light element accumulation by preventing mixing with the convecting part of the core. The temperature difference through a subadiabatic layer could be 80-300 K and carry heat fluxes through the core-mantle boundary of 0.5-23 TW, given uncertainty in core properties.

  15. Stratification effects on nonlinear elastic surface waves

    NASA Astrophysics Data System (ADS)

    Parker, D. F.

    1988-01-01

    On a homogeneous elastic half-space, linear surface waves are nondispersive. In each direction, waves having any profile travel without distortion. Nonlinearity causes intermodulation between the various wavelengths so that the signal distorts. Even when nonlinearity is small, sinusoidal profiles do not remain approximately sinusoidal. The absence of dispersion means that profiles suffer cumulative distortion, until the surface slope and strain become locally unbounded. Although this behaviour is typical of many signals, there are some signals for which intermodulation is constructive. These signals can travel coherently over large distances. For seismological applications, it is important to study the effects due to stratification. Dependence of the material constants on depth modifies the nonlinear evolution equations previously derived for homogeneous media. It has a smaller effect on higher frequencies than on lower frequencies. An approximate theory for short wavelength (high frequency) signals is introduced. Calculations show that when nonlinearity is no more important than dispersion, initially sinusoidal profiles propagate with surface slope remaining finite. When dispersion is small compared to nonlinearity, certain sharp peaked profiles can travel large distances while suffering little distortion.

  16. Clinical risk scores to guide perioperative management.

    PubMed

    Barnett, Sarah; Moonesinghe, Suneetha Ramani

    2011-08-01

    Perioperative morbidity is associated with reduced long term survival. Comorbid disease, cardiovascular illness, and functional capacity can predispose patients to adverse surgical outcomes. Accurate risk stratification would facilitate informed patient consent and identify those individuals who may benefit from specific perioperative interventions. The ideal clinical risk scoring system would be objective, accurate, economical, simple to perform, based entirely on information available preoperatively, and suitable for patients undergoing both elective and emergency surgery. The POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity) scoring systems are the most widely validated perioperative risk predictors currently utilised; however, their inclusion of intra- and postoperative variables precludes validation for preoperative risk prediction. The Charlson Index has the advantage of consisting exclusively of preoperative variables; however, its validity varies in different patient cohorts. Risk models predicting cardiac morbidity have been extensively studied, despite the relatively uncommon occurrence of postoperative cardiac events. Probably the most widely used cardiac risk score is the Lee Revised Cardiac Risk Index, although it has limited validity in some patient populations and for non-cardiac outcomes. Bespoke clinical scoring systems responding to dynamic changes in population characteristics over time, such as those developed by the American College of Surgeons National Surgical Quality Improvement Program, are more precise, but require considerable resources to implement. The combination of objective clinical variables with information from novel techniques such as cardiopulmonary exercise testing and biomarker assays, may improve the predictive precision of clinical risk scores used to guide perioperative management. PMID:21257993

  17. Stratification of Surgical Site Infection by Operative Factors and Comparison of Infection Rates after Hernia Repair

    PubMed Central

    Olsen, Margaret A.; Nickel, Katelin B.; Wallace, Anna E.; Mines, Daniel; Fraser, Victoria J.; Warren, David K.

    2015-01-01

    Objective The National Healthcare Safety Network does not risk adjust surgical site infection (SSI) rates after hernia repair by operative factors. We investigated whether operative factors are associated with risk of SSI after hernia repair. Design Retrospective cohort study. Patients Commercially-insured enrollees aged 6 months–64 years with ICD-9-CM procedure or CPT-4 codes for inguinal/femoral, umbilical, and incisional/ventral hernia repair procedures from 1/1/2004–12/31/2010. Methods SSIs within 90 days after hernia repair were identified by ICD-9-CM diagnosis codes. Chi-square and Fisher’s exact tests were used to compare SSI incidence by operative factors. Results A total of 119,973 hernia repair procedures were included in the analysis. The incidence of SSI differed significantly by anatomic site, with rates of 0.45% (352/77,666) for inguinal/femoral, 1.16% (288/24,917) for umbilical, and 4.11% (715/17,390) for incisional/ventral hernia repair. Within anatomic sites, the incidence of SSI was significantly higher for open versus laparoscopic inguinal/femoral (0.48% [295/61,142] versus 0.34% [57/16,524], p=0.020) and incisional/ventral (4.20% [701/16,699] versus 2.03% [14/691], p=0.005) hernia repairs. The rate of SSI was higher following procedures with bowel obstruction/necrosis than procedures without obstruction/necrosis for open inguinal/femoral (0.89% [48/5,422] versus 0.44% [247/55,720], p<0.001) and umbilical (1.57% [131/8,355] versus 0.95% [157/16,562], p<0.001), but not incisional/ventral hernia repair (4.01% [224/5,585] versus 4.16% [491/11,805], p=0.645). Conclusions The incidence of SSI was highest after open procedures, incisional/ventral repairs, and hernia repairs with bowel obstruction/necrosis. Our findings suggest that stratification of hernia repair SSI rates by some operative factors may be important to facilitate accurate comparison of SSI rates between facilities. PMID:25695175

  18. Ice duration, winter stratification, and mixing behavior of subalpine lakes in western Maine

    NASA Astrophysics Data System (ADS)

    Daly, J.; Adams, S.; Abrams, R.; Engel, B.

    2011-12-01

    The timing and duration of both winter and summer periods of stratification periods is not well known for subalpine ponds in the northeastern United States. The remote nature of many of these lakes precludes detailed manual monitoring during the winter and the visual identification of major ice phenological events. These lakes are associated with ecological niches at or near their local elevation maximum that may be at risk due to climate change; historic ice-out records for larger regional lakes indicates a significant trend toward earlier ice-out in response to climate warming. We are using low-cost data loggers to develop high-resolution records characterizing water temperature variability at multiple depths in fifteen lakes 600 - 1000 m elevation. These lakes are located along a 175 km transect in western Maine; most are along the Appalachian Trail. The loggers are recording sub-hourly water temperature and light at the surface, two meters depth, and the bottom of each lake. The timing and duration of winter stratification and ice cover on these lakes are determined by distinctive temperature patterns recorded by the data loggers. The onset of winter stratification is marked by the expected temperature inversion and a slowly increasing hypolimnetic temperature; ice-on follows and is represented by the transition from daily heating cycles to a steady temperature over several days as the ice freezes in around the near-surface logger and energy loss is accomplished through a phase change rather than a drop in temperature. Once the ice is established, temperatures recorded by the near-surface logger vary daily, and are frequently below freezing in response to changing air temperature. Evaluation of winter 2009-2011 records shows that the duration of winter stratification exceeds ice duration at nearly every site. The timing of the onset of stratification is nearly uniform across the study area within each year of data, suggesting a nearly simultaneous response to

  19. Summer Stratification and Fall Overturn--In a Jar.

    ERIC Educational Resources Information Center

    Foley, Arlene F.

    1984-01-01

    Provided are procedures for a demonstration which illustrates the concept of summer stratification of lakes in the temperate zone as maintained by thermal resistance to mixing. The demonstration requires only food coloring, water, and common laboratory equipment. (JN)

  20. A new stratification of mourning dove call-count routes

    USGS Publications Warehouse

    Blankenship, L.H.; Humphrey, A.B.; MacDonald, D.

    1971-01-01

    The mourning dove (Zenaidura macroura) call-count survey is a nationwide audio-census of breeding mourning doves. Recent analyses of the call-count routes have utilized a stratification based upon physiographic regions of the United States. An analysis of 5 years of call-count data, based upon stratification using potential natural vegetation, has demonstrated that this uew stratification results in strata with greater homogeneity than the physiographic strata, provides lower error variance, and hence generates greatet precision in the analysis without an increase in call-count routes. Error variance was reduced approximately 30 percent for the contiguous United States. This indicates that future analysis based upon the new stratification will result in an increased ability to detect significant year-to-year changes.

  1. Accounting for population stratification in DNA methylation studies.

    PubMed

    Barfield, Richard T; Almli, Lynn M; Kilaru, Varun; Smith, Alicia K; Mercer, Kristina B; Duncan, Richard; Klengel, Torsten; Mehta, Divya; Binder, Elisabeth B; Epstein, Michael P; Ressler, Kerry J; Conneely, Karen N

    2014-04-01

    DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as population stratification will need to be addressed. It is well-documented that failure to adjust for population stratification can lead to false positives in genetic association studies, but population stratification is often unaccounted for in DNA methylation studies. Here, we propose several approaches to correct for population stratification using principal components (PCs) from different subsets of genome-wide methylation data. We first illustrate the potential for confounding due to population stratification by demonstrating widespread associations between DNA methylation and race in 388 individuals (365 African American and 23 Caucasian). We subsequently evaluate the performance of our PC-based approaches and other methods in adjusting for confounding due to population stratification. Our simulations show that (1) all of the methods considered are effective at removing inflation due to population stratification, and (2) maximum power can be obtained with single-nucleotide polymorphism (SNP)-based PCs, followed by methylation-based PCs, which outperform both surrogate variable analysis and genomic control. Among our different approaches to computing methylation-based PCs, we find that PCs based on CpG sites chosen for their potential to proxy nearby SNPs can provide a powerful and computationally efficient approach to adjust for population stratification in DNA methylation studies when genome-wide SNP data are unavailable. PMID:24478250

  2. Modeling tidal circulation and stratification in Skagit River estuary using an unstructured grid ocean model

    NASA Astrophysics Data System (ADS)

    Yang, Zhaoqing; Khangaonkar, Tarang

    Tidal circulation and river plume dynamics in shallow-water estuarine systems with large intertidal zones are complex. Strong asymmetries in tidal currents and stratification often occur in the intertidal zones and subtidal channels over a tidal cycle. The Skagit River is the largest estuary with respect to the discharge of a significant amount of freshwater and sediment into Puget Sound, Washington. It consists of a large intertidal zone with multiple tidal channels near the mouth of the estuary. To simulate the tidal circulation and salinity stratification accurately in the intertidal region, an unstructured grid numerical model with wetting-drying capability and the capability to accurately represent the bathymetry of tidal flats and the geometry of shallow distributary channels is necessary. In this paper, a modeling study for the Skagit River estuary using a three-dimensional unstructured grid, finite-volume coastal ocean model (FVCOM) supported by high-resolution LIDAR data is presented. The hydrodynamic model was validated with observed water surface elevation, velocity, and salinity data over spring and neap tidal cycles under low-river-flow and high-river-flow conditions. Wetting and drying processes in the intertidal zone and strong stratification in the estuary were simulated successfully by the model. Model results indicate that the Skagit River estuary is a highly stratified estuary, but destratification can occur during flood tide. Tides and baroclinic motion are the dominant forcing in the Skagit River estuary, but strong wind events can affect the currents in the intertidal zone significantly. Preliminary analysis also indicated that the salinity intrusion length scale is proportional to the river flow to the -¼ power.

  3. Initial clinical validation of Health Heritage, a patient-facing tool for personal and family history collection and cancer risk assessment.

    PubMed

    Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A

    2016-04-01

    Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97 % (sensitivity 98 % and specificity 88 %). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75 %, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team. PMID:26711915

  4. Identification of the high risk emergency surgical patient: Which risk prediction model should be used?

    PubMed Central

    Stonelake, Stephen; Thomson, Peter; Suggett, Nigel

    2015-01-01

    Introduction National guidance states that all patients having emergency surgery should have a mortality risk assessment calculated on admission so that the ‘high risk’ patient can receive the appropriate seniority and level of care. We aimed to assess if peri-operative risk scoring tools could accurately calculate mortality and morbidity risk. Methods Mortality risk scores for 86 consecutive emergency laparotomies, were calculated using pre-operative (ASA, Lee index) and post-operative (POSSUM, P-POSSUM and CR-POSSUM) risk calculation tools. Morbidity risk scores were calculated using the POSSUM predicted morbidity and compared against actual morbidity according to the Clavien–Dindo classification. Results The actual mortality was 10.5%. The average predicted risk scores for all laparotomies were: ASA 26.5%, Lee Index 2.5%, POSSUM 29.5%, P-POSSUM 18.5%, CR-POSSUM 10.5%. Complications occurred following 67 laparotomies (78%). The majority (51%) of complications were classified as Clavien–Dindo grade 2–3 (non-life-threatening). Patients having a POSSUM morbidity risk of greater than 50% developed significantly more life-threatening complications (CD 4–5) compared with those who predicted less than or equal to 50% morbidity risk (P = 0.01). Discussion Pre-operative risk stratification remains a challenge because the Lee Index under-predicts and ASA over-predicts mortality risk. Post-operative risk scoring using the CR-POSSUM is more accurate and we suggest can be used to identify patients who require intensive care post-operatively. Conclusions In the absence of accurate risk scoring tools that can be used on admission to hospital it is not possible to reliably audit the achievement of national standards of care for the ‘high-risk’ patient. PMID:26468369

  5. Comparison of risk assessment strategies for not-high-risk pulmonary embolism.

    PubMed

    Hobohm, Lukas; Hellenkamp, Kristian; Hasenfuß, Gerd; Münzel, Thomas; Konstantinides, Stavros; Lankeit, Mareike

    2016-04-01

    We compared the prognostic performance of the 2014 European Society of Cardiology (ESC) risk stratification algorithm with the previous 2008 ESC algorithm, the Bova score and the modified FAST score (based on a positive heart-type fatty acid-binding protein (H-FABP) test, syncope and tachycardia, modified using high-sensitivity troponin T instead of H-FABP) in 388 normotensive pulmonary embolism patients included in a single-centre cohort study.Overall, 25 patients (6.4%) had an adverse 30-day outcome. Regardless of the score or algorithm used, the rate of an adverse outcome was highest in the intermediate-high-risk classes, while all patients classified as low-risk had a favourable outcome (no pulmonary embolism-related deaths, 0-1.4% adverse outcome). The area under the curve for predicting an adverse outcome was higher for the 2014 ESC algorithm (0.76, 95% CI 0.68-0.84) compared with the 2008 ESC algorithm (0.65, 95% CI 0.56-0.73) and highest for the modified FAST score (0.82, 95% CI 0.75-0.89). Patients classified as intermediate-high-risk by the 2014 ESC algorithm had a 8.9-fold increased risk for an adverse outcome (3.2-24.2, p<0.001 compared with intermediate-low- and low-risk patients), while the highest OR was observed for a modified FAST score ≥3 points (OR 15.9, 95% CI 5.3-47.6, p<0.001).The 2014 ESC algorithm improves risk stratification of not-high-risk pulmonary embolism compared with the 2008 ESC algorithm. All scores and algorithms accurately identified low-risk patients, while the modified FAST score appears more suitable to identify intermediate-high-risk patients. PMID:26743479

  6. Grading More Accurately

    ERIC Educational Resources Information Center

    Rom, Mark Carl

    2011-01-01

    Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

  7. Comparison of Accuracy of Diabetes Risk Score and Components of the Metabolic Syndrome in Assessing Risk of Incident Type 2 Diabetes in Inter99 Cohort

    PubMed Central

    Shafizadeh, Tracy B.; Moler, Edward J.; Kolberg, Janice A.; Nguyen, Uyen Thao; Hansen, Torben; Jorgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

    2011-01-01

    Background Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM); factors of metabolic syndrome (MetS) and a previously developed diabetes risk score, PreDx® Diabetes Risk Score (DRS). DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood. Methodology/Principal Findings DRS was evaluated in baseline serum samples from 4,128 non-diabetic subjects in the Inter99 cohort (Danes aged 30–60) for whom diabetes outcomes at 5 years were known. Subjects were classified as having MetS based on the presence of at least 3 MetS risk factors in baseline clinical data. The sensitivity and false positive rate for predicting diabetes using MetS was compared to DRS. When the sensitivity was fixed to match MetS, DRS had a significantly lower false positive rate. Similarly, when the false positive rate was fixed to match MetS, DRS had a significantly higher specificity. In further analyses, subjects were classified by presence of 0–2, 3 or 4–5 risk factors with matching proportions of subjects distributed among three DRS groups. Comparison between the two risk stratification schemes, MetS risk factors and DRS, were evaluated using Net Reclassification Improvement (NRI). Comparing risk stratification by DRS to MetS factors in the total population, the NRI was 0.146 (p = 0.008) demonstrating DRS provides significantly improved stratification. Additionally, the relative risk of T2DM differed by 15 fold between the low and high DRS risk groups, but only 8-fold between the low and high risk MetS groups. Conclusions/Significance DRS provides a more accurate assessment of risk for diabetes than MetS. This improved performance may allow clinicians to focus preventive strategies on those most in need of urgent intervention. PMID:21829540

  8. Patient Stratification for Preventive Care in Dentistry

    PubMed Central

    Giannobile, W.V.; Braun, T.M.; Caplis, A.K.; Doucette-Stamm, L.; Duff, G.W.; Kornman, K.S.

    2013-01-01

    Prevention reduces tooth loss, but little evidence supports biannual preventive care for all adults. We used risk-based approaches to test tooth loss association with 1 vs. 2 annual preventive visits in high-risk (HiR) and low-risk (LoR) patients. Insurance claims for 16 years for 5,117 adults were evaluated retrospectively for tooth extraction events. Patients were classified as HiR for progressive periodontitis if they had ≥ 1 of the risk factors (RFs) smoking, diabetes, interleukin-1 genotype; or as LoR if no RFs. LoR event rates were 13.8% and 16.4% for 2 or 1 annual preventive visits (absolute risk reduction, 2.6%; 95%CI, 0.5% to 5.8%; p = .092). HiR event rates were 16.9% and 22.1% for 2 and 1 preventive visits (absolute risk reduction, 5.2%; 95%CI, 1.8% to 8.4%; p = .002). Increasing RFs increased events (p < .001). Oral health care costs were not increased by any single RF, regardless of prevention frequency (p > .41), but multiple RFs increased costs vs. no (p < .001) or 1 RF (p = .001). For LoR individuals, the association between preventive dental visits and tooth loss was not significantly different whether the frequency was once or twice annually. A personalized medicine approach combining gene biomarkers with conventional risk factors to stratify populations may be useful in resource allocation for preventive dentistry (ClinicalTrials.gov, NCT01584479). PMID:23752171

  9. Stratification of colloidal aggregation coupled with sedimentation.

    PubMed

    González, Agustín E

    2006-12-01

    One of the consequences of sedimentation in colloidal aggregation is the stratification of the system in the sense that, after a sufficiently long elapsed time, the large clusters lie preferentially at the bottom zones of the confinement prism, and the structural and dynamical quantities describing the aggregates depend on the depth at which they are measured. A few years ago a computer simulation using particles for colloidal aggregation coupled with sedimentation was proposed by the author [A. E. González, Phys. Rev. Lett. 86, 1243 (2001)]. In that simulation, due to computational limitations, the mentioned quantities were averaged over all clusters in the prism, independently of the depth at which they were located, in order to have good statistics for the evaluation of the cluster fractal dimension and the cluster size distribution function. In this work we present a computer simulation using particles of colloidal aggregation coupled with sedimentation, for which the clusters in the simulation box represent those clusters inside a layer at a fixed depth and of arbitrary thickness in the prism. It would then be possible to compare the results with an eventual validation experiment, in which an aggregating sample is sipped out with a pipette at a fixed depth in the prism and subjected to further studies, or with a light scattering study in which the laser beam is focused at a fixed depth in the system. We confirm the acceleration of the aggregation rate, followed by a slowing down, compared with an aggregating system driven purely by diffusion (DLCA). In the present system, the large clusters when drifting downwards sweep smaller ones, which in turn occlude the holes and cavities of these large clusters, increasing in this way their compacticity. We also confirm that (i) in some cases of sedimentation strengths and layer depths, the mean width (perpendicular to the gravitational field direction) and the mean height of the large settling clusters scale with the

  10. Accurate monotone cubic interpolation

    NASA Technical Reports Server (NTRS)

    Huynh, Hung T.

    1991-01-01

    Monotone piecewise cubic interpolants are simple and effective. They are generally third-order accurate, except near strict local extrema where accuracy degenerates to second-order due to the monotonicity constraint. Algorithms for piecewise cubic interpolants, which preserve monotonicity as well as uniform third and fourth-order accuracy are presented. The gain of accuracy is obtained by relaxing the monotonicity constraint in a geometric framework in which the median function plays a crucial role.

  11. Accurate Finite Difference Algorithms

    NASA Technical Reports Server (NTRS)

    Goodrich, John W.

    1996-01-01

    Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

  12. Accurate inference of local phased ancestry of modern admixed populations.

    PubMed

    Ma, Yamin; Zhao, Jian; Wong, Jian-Syuan; Ma, Li; Li, Wenzhi; Fu, Guoxing; Xu, Wei; Zhang, Kui; Kittles, Rick A; Li, Yun; Song, Qing

    2014-01-01

    Population stratification is a growing concern in genetic-association studies. Averaged ancestry at the genome level (global ancestry) is insufficient for detecting the population substructures and correcting population stratifications in association studies. Local and phase stratification are needed for human genetic studies, but current technologies cannot be applied on the entire genome data due to various technical caveats. Here we developed a novel approach (aMAP, ancestry of Modern Admixed Populations) for inferring local phased ancestry. It took about 3 seconds on a desktop computer to finish a local ancestry analysis for each human genome with 1.4-million SNPs. This method also exhibits the scalability to larger datasets with respect to the number of SNPs, the number of samples, and the size of reference panels. It can detect the lack of the proxy of reference panels. The accuracy was 99.4%. The aMAP software has a capacity for analyzing 6-way admixed individuals. As the biomedical community continues to expand its efforts to increase the representation of diverse populations, and as the number of large whole-genome sequence datasets continues to grow rapidly, there is an increasing demand on rapid and accurate local ancestry analysis in genetics, pharmacogenomics, population genetics, and clinical diagnosis. PMID:25052506

  13. Social Stratification and Cooperative Behavior in Spatial Prisoners' Dilemma Games.

    PubMed

    Lu, Peng; Zheng, Xiaoping

    2015-01-01

    It has been a long-lasting pursuit to promote cooperation, and this study aims to promote cooperation via the combination of social stratification and the spatial prisoners' dilemma game. It is previously assumed that agents share the identical payoff matrix, but the stratification or diversity exists and exerts influences in real societies. Thus, two additional classes, elites and scoundrels, derive from and coexist with the existing class, commons. Three classes have different payoff matrices. We construct a model where agents play the prisoners' dilemma game with neighbors. It indicates that stratification and temptation jointly influence cooperation. Temptation permanently reduces cooperation; elites play a positive role in promoting cooperation while scoundrels undermine it. As the temptation getting larger and larger, elites play a more and more positive and critical role while scoundrels' negative effect becomes weaker and weaker, and it is more obvious when temptation goes beyond its threshold. PMID:26173029

  14. Thermal Stratification by Steam Condensation of RCIC in Suppression Pool

    NASA Astrophysics Data System (ADS)

    Okamoto, Koji; Song, Daehun; Erkan, Nejdet

    2013-11-01

    In Fukushima-Daiichi NPP accident, the RCIC operated more than a couple of days. The steam condensation at the supression pool may cause the thermal-stratification. The phenomena may affects on the capacity of RCIC and also the progression of the event in case of Severe Accident. To investigate the mechanism of formation of thermal stratification and the effects in suppression pool, down-sized SP model was designed and time resolved temperature and pressure data were acquired. During the experiments well-established stationary thermal stratification was detected since the start of steam injection. PIV was carried out to figure out the natural circulation due to the buoyancy and the mixing interface, which decides the pressure suppression capacity of suppression pool (SP). Numerical simulation was carried out with ANSYS CFX 14.0 in single phase and validated with experimental data.

  15. Social Stratification and Cooperative Behavior in Spatial Prisoners' Dilemma Games

    PubMed Central

    Lu, Peng; Zheng, Xiaoping

    2015-01-01

    It has been a long-lasting pursuit to promote cooperation, and this study aims to promote cooperation via the combination of social stratification and the spatial prisoners’ dilemma game. It is previously assumed that agents share the identical payoff matrix, but the stratification or diversity exists and exerts influences in real societies. Thus, two additional classes, elites and scoundrels, derive from and coexist with the existing class, commons. Three classes have different payoff matrices. We construct a model where agents play the prisoners’ dilemma game with neighbors. It indicates that stratification and temptation jointly influence cooperation. Temptation permanently reduces cooperation; elites play a positive role in promoting cooperation while scoundrels undermine it. As the temptation getting larger and larger, elites play a more and more positive and critical role while scoundrels’ negative effect becomes weaker and weaker, and it is more obvious when temptation goes beyond its threshold. PMID:26173029

  16. Density stratification effects in sand-bed rivers

    USGS Publications Warehouse

    Wright, S.; Parker, G.

    2004-01-01

    In this paper the effects of density stratification in sand-bed rivers are studied by the application of a model of vertical velocity and concentration profiles, coupled through the use of a turbulence closure that retains the buoyancy terms. By making the governing equations dimensionless, it is revealed that the slope is the additional dimensionless parameter introduced by inclusion of the buoyancy terms. The primary new finding is that in general density stratification effects tend to be greater in large, low-slope rivers than in their smaller, steeper brethren. Under high flow conditions the total suspended load and size distribution of suspended sediment can be significantly affected by density stratification, and should be accounted for in any general theory of suspended transport. ?? ASCE.

  17. Auto-stratification in drying colloidal dispersions: a diffusive model.

    PubMed

    Trueman, R E; Lago Domingues, E; Emmett, S N; Murray, M W; Routh, A F

    2012-07-01

    The mechanism by which the particles in a drying film come into close packing during solvent evaporation has an important role to play in the final film morphology. During drying the particles can develop non-uniform concentrations across the vertical height of the film, depending on their diffusion rate. By applying the principles of classical diffusion mechanics to a hard sphere system, a theory for this novel method of stratification during drying of a two component film has been derived. The model is dependent on the particle Peclet numbers and when one is above unity and the other below, maximum stratification is observed. PMID:22503626

  18. Simulating 2,368 temperate lakes reveals weak coherence in stratification phenology

    USGS Publications Warehouse

    Read, Jordan S.; Winslow, Luke A.; Hansen, Gretchen J. A.; Van Den Hoek, Jamon; Hanson, Paul C.; Bruce, Louise C; Markfort, Corey D

    2014-01-01

    Changes in water temperatures resulting from climate warming can alter the structure and function of aquatic ecosystems. Lake-specific physical characteristics may play a role in mediating individual lake responses to climate. Past mechanistic studies of lake-climate interactions have simulated generic lake classes at large spatial scales or performed detailed analyses of small numbers of real lakes. Understanding the diversity of lake responses to climate change across landscapes requires a hybrid approach that couples site-specific lake characteristics with broad-scale environmental drivers. This study provides a substantial advancement in lake ecosystem modeling by combining open-source tools with freely available continental-scale data to mechanistically model daily temperatures for 2,368 Wisconsin lakes over three decades (1979-2011). The model accurately predicted observed surface layer temperatures (RMSE: 1.74°C) and the presence/absence of stratification (81.1% agreement). Among-lake coherence was strong for surface temperatures and weak for the timing of stratification, suggesting individual lake characteristics mediate some - but not all - ecologically relevant lake responses to climate.

  19. Accurate measurement of time

    NASA Astrophysics Data System (ADS)

    Itano, Wayne M.; Ramsey, Norman F.

    1993-07-01

    The paper discusses current methods for accurate measurements of time by conventional atomic clocks, with particular attention given to the principles of operation of atomic-beam frequency standards, atomic hydrogen masers, and atomic fountain and to the potential use of strings of trapped mercury ions as a time device more stable than conventional atomic clocks. The areas of application of the ultraprecise and ultrastable time-measuring devices that tax the capacity of modern atomic clocks include radio astronomy and tests of relativity. The paper also discusses practical applications of ultraprecise clocks, such as navigation of space vehicles and pinpointing the exact position of ships and other objects on earth using the GPS.

  20. Accurate quantum chemical calculations

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1989-01-01

    An important goal of quantum chemical calculations is to provide an understanding of chemical bonding and molecular electronic structure. A second goal, the prediction of energy differences to chemical accuracy, has been much harder to attain. First, the computational resources required to achieve such accuracy are very large, and second, it is not straightforward to demonstrate that an apparently accurate result, in terms of agreement with experiment, does not result from a cancellation of errors. Recent advances in electronic structure methodology, coupled with the power of vector supercomputers, have made it possible to solve a number of electronic structure problems exactly using the full configuration interaction (FCI) method within a subspace of the complete Hilbert space. These exact results can be used to benchmark approximate techniques that are applicable to a wider range of chemical and physical problems. The methodology of many-electron quantum chemistry is reviewed. Methods are considered in detail for performing FCI calculations. The application of FCI methods to several three-electron problems in molecular physics are discussed. A number of benchmark applications of FCI wave functions are described. Atomic basis sets and the development of improved methods for handling very large basis sets are discussed: these are then applied to a number of chemical and spectroscopic problems; to transition metals; and to problems involving potential energy surfaces. Although the experiences described give considerable grounds for optimism about the general ability to perform accurate calculations, there are several problems that have proved less tractable, at least with current computer resources, and these and possible solutions are discussed.

  1. USA Stratified Monopoly: A Simulation Game about Social Class Stratification

    ERIC Educational Resources Information Center

    Fisher, Edith M.

    2008-01-01

    Effectively teaching college students about social class stratification is a difficult challenge. Explanations for this difficulty tend to focus on the students who often react with resistance, paralysis, or rage. Sociologists have been using games and simulations as alternative methods for several decades to teach about these sensitive subjects.…

  2. Picturing Sex Education: Notes on the Politics of Visual Stratification

    ERIC Educational Resources Information Center

    Janssen, Diederik F.

    2006-01-01

    This paper addresses the scarcity of research on depictions and layout in sex education materials. It is argued that pictures and layout can inform an analysis of social stratification based on visual access. This process of social organization is located using four theoretical models. However these models do not lend themselves to a close reading…

  3. Academic Stratification and Endemic Conflict: Remedial Education Policy at CUNY.

    ERIC Educational Resources Information Center

    Gumport, Patricia J.; Bastedo, Michael N.

    2001-01-01

    Examines remedial education policy change at City University of New York (CUNY) both in historical context and from the perspective of system design. Interprets the policy to phase out remedial education in CUNY senior colleges as strategy to create "more of a system" by increasing differentiation of missions and stratification among campuses…

  4. Stratification of centrifuged amoeba nuclei investigated by electron microscopy

    NASA Technical Reports Server (NTRS)

    Breyer, E. P.; Daniels, E. W.

    1968-01-01

    Study establishes a relationship between radioresistance and the nucleolar stratification characteristics of various amoeba species. Two species of fresh water amoeba are studied with the electron microscope. The report discusses the nature of nucleolar layers and their possible relationship to the differences in radiosensitivity of the two amoeba species.

  5. Improved fiber optic device for in situ determination of electrolyte stratification in lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Gajdátsy, G.; Benedek, F.; Kokavecz, J.; Szabó, G.; Kornis, J.

    2009-12-01

    A three-channel, highly sensitive, fiber optic device is presented to measure acid concentration in lead-acid batteries during their operation. The refractive index and thereby the concentration of sulfuric acid is measured by a bent, silica glass fiber tip, stripped off its cladding. Sensor heads of the device are small enough to be inserted at different positions in the cell of an ordinary, flooded lead-acid battery. Measuring the concentration of the electrolyte at different depths of the battery cell, acid stratification can be accurately determined. During the test of the instrument, about 0.3 Hz temporal and 0.05 wt % concentration resolutions were achieved while the temperature drift was found to be -0.25 wt %/°C.

  6. Improved fiber optic device for in situ determination of electrolyte stratification in lead-acid batteries.

    PubMed

    Gajdátsy, G; Benedek, F; Kokavecz, J; Szabó, G; Kornis, J

    2009-12-01

    A three-channel, highly sensitive, fiber optic device is presented to measure acid concentration in lead-acid batteries during their operation. The refractive index and thereby the concentration of sulfuric acid is measured by a bent, silica glass fiber tip, stripped off its cladding. Sensor heads of the device are small enough to be inserted at different positions in the cell of an ordinary, flooded lead-acid battery. Measuring the concentration of the electrolyte at different depths of the battery cell, acid stratification can be accurately determined. During the test of the instrument, about 0.3 Hz temporal and 0.05 wt % concentration resolutions were achieved while the temperature drift was found to be -0.25 wt %/degrees C. PMID:20059171

  7. Stratification and therapeutic potential of PML in metastatic breast cancer

    PubMed Central

    Martín-Martín, Natalia; Piva, Marco; Urosevic, Jelena; Aldaz, Paula; Sutherland, James D.; Fernández-Ruiz, Sonia; Arreal, Leire; Torrano, Verónica; Cortazar, Ana R.; Planet, Evarist; Guiu, Marc; Radosevic-Robin, Nina; Garcia, Stephane; Macías, Iratxe; Salvador, Fernando; Domenici, Giacomo; Rueda, Oscar M.; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Zúñiga-García, Patricia; Caro-Maldonado, Alfredo; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Varela-Rey, Marta; Martínez-Chantar, Maria Luz; Anguita, Juan; Ibrahim, Yasir H.; Scaltriti, Maurizio; Lawrie, Charles H.; Aransay, Ana M.; Iovanna, Juan L.; Baselga, Jose; Caldas, Carlos; Barrio, Rosa; Serra, Violeta; dM Vivanco, Maria; Matheu, Ander; Gomis, Roger R.; Carracedo, Arkaitz

    2016-01-01

    Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification. PMID:27553708

  8. Low gravity thermal stratification of liquid helium on SHOOT

    NASA Astrophysics Data System (ADS)

    Shirron, P. J.; Dipirro, M. J.

    Estimates of the extent and impact of thermal stratification are presented as well as predictions of the behavior of the HeI/HeII boundary. Although thermal stratification of cryogens can be problematic and lead to their inefficient use in low gravity, for SHOOT the occurrence is beneficial both during ground hold and in orbit and presents no hazards. On the ground the parasitic heat load is both reduced and more efficiently removed. In orbit the pumpdown proceeds at a much more rapid rate, allowing orbital operations to begin earlier. The thermal conductivity of the aluminum tank and the normal liquid plus cooling at the liquid/vapor interface as the vapor bubble grows are sufficient to prevent undesirably high vapor pressures in the tank.

  9. Fatigue of LMFBR piping due to flow stratification

    SciTech Connect

    Woodward, W.S.

    1983-01-01

    Flow stratification due to reverse flow was simulated in a 1/5-scale water model of a LMFBR primary pipe loop. The stratified flow was observed to have a dynamic interface region which oscillated in a wave pattern. The behavior of the interface was characterized in terms of location, local temperature fluctuation and duration for various reverse flow conditions. A structural assessment was performed to determine the effects of stratified flow on the fatigue life of the pipe. Both the static and dynamic aspects of flow stratification were examined. The dynamic interface produces thermal striping on the inside of the pipe wall which is shown to have the most deleterious effect on the pipe wall and produce significant fatigue damage relative to a static interface.

  10. Stratification and therapeutic potential of PML in metastatic breast cancer.

    PubMed

    Martín-Martín, Natalia; Piva, Marco; Urosevic, Jelena; Aldaz, Paula; Sutherland, James D; Fernández-Ruiz, Sonia; Arreal, Leire; Torrano, Verónica; Cortazar, Ana R; Planet, Evarist; Guiu, Marc; Radosevic-Robin, Nina; Garcia, Stephane; Macías, Iratxe; Salvador, Fernando; Domenici, Giacomo; Rueda, Oscar M; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Zúñiga-García, Patricia; Caro-Maldonado, Alfredo; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Varela-Rey, Marta; Martínez-Chantar, Maria Luz; Anguita, Juan; Ibrahim, Yasir H; Scaltriti, Maurizio; Lawrie, Charles H; Aransay, Ana M; Iovanna, Juan L; Baselga, Jose; Caldas, Carlos; Barrio, Rosa; Serra, Violeta; Vivanco, Maria dM; Matheu, Ander; Gomis, Roger R; Carracedo, Arkaitz

    2016-01-01

    Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification. PMID:27553708

  11. Dynamic Stratification in Drying Films of Colloidal Mixtures.

    PubMed

    Fortini, Andrea; Martín-Fabiani, Ignacio; De La Haye, Jennifer Lesage; Dugas, Pierre-Yves; Lansalot, Muriel; D'Agosto, Franck; Bourgeat-Lami, Elodie; Keddie, Joseph L; Sear, Richard P

    2016-03-18

    In simulations and experiments, we study the drying of films containing mixtures of large and small colloidal particles in water. During drying, the mixture stratifies into a layer of the larger particles at the bottom with a layer of the smaller particles on top. We developed a model to show that a gradient in osmotic pressure, which develops dynamically during drying, is responsible for the segregation mechanism behind stratification. PMID:27035324

  12. Dynamic Stratification in Drying Films of Colloidal Mixtures

    NASA Astrophysics Data System (ADS)

    Fortini, Andrea; Martín-Fabiani, Ignacio; De La Haye, Jennifer Lesage; Dugas, Pierre-Yves; Lansalot, Muriel; D'Agosto, Franck; Bourgeat-Lami, Elodie; Keddie, Joseph L.; Sear, Richard P.

    2016-03-01

    In simulations and experiments, we study the drying of films containing mixtures of large and small colloidal particles in water. During drying, the mixture stratifies into a layer of the larger particles at the bottom with a layer of the smaller particles on top. We developed a model to show that a gradient in osmotic pressure, which develops dynamically during drying, is responsible for the segregation mechanism behind stratification.

  13. Potential Impacts of Offshore Wind Farms on North Sea Stratification.

    PubMed

    Carpenter, Jeffrey R; Merckelbach, Lucas; Callies, Ulrich; Clark, Suzanna; Gaslikova, Lidia; Baschek, Burkard

    2016-01-01

    Advances in offshore wind farm (OWF) technology have recently led to their construction in coastal waters that are deep enough to be seasonally stratified. As tidal currents move past the OWF foundation structures they generate a turbulent wake that will contribute to a mixing of the stratified water column. In this study we show that the mixing generated in this way may have a significant impact on the large-scale stratification of the German Bight region of the North Sea. This region is chosen as the focus of this study since the planning of OWFs is particularly widespread. Using a combination of idealised modelling and in situ measurements, we provide order-of-magnitude estimates of two important time scales that are key to understanding the impacts of OWFs: (i) a mixing time scale, describing how long a complete mixing of the stratification takes, and (ii) an advective time scale, quantifying for how long a water parcel is expected to undergo enhanced wind farm mixing. The results are especially sensitive to both the drag coefficient and type of foundation structure, as well as the evolution of the pycnocline under enhanced mixing conditions-both of which are not well known. With these limitations in mind, the results show that OWFs could impact the large-scale stratification, but only when they occupy extensive shelf regions. They are expected to have very little impact on large-scale stratification at the current capacity in the North Sea, but the impact could be significant in future large-scale development scenarios. PMID:27513754

  14. Potential Impacts of Offshore Wind Farms on North Sea Stratification

    PubMed Central

    Carpenter, Jeffrey R.; Merckelbach, Lucas; Callies, Ulrich; Clark, Suzanna; Gaslikova, Lidia; Baschek, Burkard

    2016-01-01

    Advances in offshore wind farm (OWF) technology have recently led to their construction in coastal waters that are deep enough to be seasonally stratified. As tidal currents move past the OWF foundation structures they generate a turbulent wake that will contribute to a mixing of the stratified water column. In this study we show that the mixing generated in this way may have a significant impact on the large-scale stratification of the German Bight region of the North Sea. This region is chosen as the focus of this study since the planning of OWFs is particularly widespread. Using a combination of idealised modelling and in situ measurements, we provide order-of-magnitude estimates of two important time scales that are key to understanding the impacts of OWFs: (i) a mixing time scale, describing how long a complete mixing of the stratification takes, and (ii) an advective time scale, quantifying for how long a water parcel is expected to undergo enhanced wind farm mixing. The results are especially sensitive to both the drag coefficient and type of foundation structure, as well as the evolution of the pycnocline under enhanced mixing conditions—both of which are not well known. With these limitations in mind, the results show that OWFs could impact the large-scale stratification, but only when they occupy extensive shelf regions. They are expected to have very little impact on large-scale stratification at the current capacity in the North Sea, but the impact could be significant in future large-scale development scenarios. PMID:27513754

  15. "Stratifiability index" - A quantitative assessment of acid stratification in flooded lead acid batteries

    NASA Astrophysics Data System (ADS)

    Schulte, Dominik; Sauer, Dirk Uwe; Ebner, Ellen; Börger, Alexander; Gose, Sven; Wenzl, Heinz

    2014-12-01

    A methodology is presented to quantify acid stratification in flooded lead acid batteries and compare different types of batteries regardless of their design features and size by means of the proposed "stratifiability index". This index describes to what degree acid stratification develops in flooded lead acid batteries. Different test procedures are proposed which induce severe acid stratification within 48 h and lead to significantly different degrees of acid stratification. The test procedures are intended to assist in the development and selection of batteries which are less prone to develop severe acid stratification.

  16. Urban noise functional stratification for estimating average annual sound level.

    PubMed

    Rey Gozalo, Guillermo; Barrigón Morillas, Juan Miguel; Prieto Gajardo, Carlos

    2015-06-01

    Road traffic noise causes many health problems and the deterioration of the quality of urban life; thus, adequate spatial noise and temporal assessment methods are required. Different methods have been proposed for the spatial evaluation of noise in cities, including the categorization method. Until now, this method has only been applied for the study of spatial variability with measurements taken over a week. In this work, continuous measurements of 1 year carried out in 21 different locations in Madrid (Spain), which has more than three million inhabitants, were analyzed. The annual average sound levels and the temporal variability were studied in the proposed categories. The results show that the three proposed categories highlight the spatial noise stratification of the studied city in each period of the day (day, evening, and night) and in the overall indicators (L(And), L(Aden), and L(A24)). Also, significant differences between the diurnal and nocturnal sound levels show functional stratification in these categories. Therefore, this functional stratification offers advantages from both spatial and temporal perspectives by reducing the sampling points and the measurement time. PMID:26093410

  17. Effect of Stratification on Surface Properties of Corneal Epithelial Cells

    PubMed Central

    Yáñez-Soto, Bernardo; Leonard, Brian C.; Raghunathan, Vijay Krishna; Abbott, Nicholas L.; Murphy, Christopher J.

    2015-01-01

    Purpose The purpose of this study was to determine the influence of mucin expression in an immortalized human corneal epithelial cell line (hTCEpi) on the surface properties of cells, such as wettability, contact angle, and surface heterogeneity. Methods hTCEpi cells were cultured to confluence in serum-free medium. The medium was then replaced by stratification medium to induce mucin biosynthesis. The mucin expression profile was analyzed using quantitative PCR and Western blotting. Contact angles were measured using a two-immiscible liquid method, and contact angle hysteresis was evaluated by tilting the apparatus and recording advancing and receding contact angles. The spatial distribution of mucins was evaluated with fluorescently labeled lectin. Results hTCEpi cells expressed the three main ocular mucins (MUC1, MUC4, and MUC16) with a maximum between days 1 and 3 of the stratification process. Upon stratification, cells caused a very significant increase in contact angle hysteresis, suggesting the development of spatially discrete and heterogeneously distributed surface features, defined by topography and/or chemical functionality. Although atomic force microscopy measurements showed no formation of appreciable topographic features on the surface of the cells, we observed a significant increase in surface chemical heterogeneity. Conclusions The surface chemical heterogeneity of the corneal epithelium may influence the dynamic behavior of tear film by “pinning” the contact line between the cellular surface and aqueous tear film. Engineering the surface properties of corneal epithelium could potentially lead to novel treatments in dry eye disease. PMID:26747762

  18. On the role of sea ice for Southern Ocean stratification

    NASA Astrophysics Data System (ADS)

    Haumann, F. Alexander; Münnich, Matthias; Gruber, Nicolas

    2013-04-01

    The formation, subsequent lateral transport, and melt of sea ice represents a key process for the determination of upper ocean stratification in the Southern Ocean. Sea ice is transported northward in large parts of the Southern Ocean by strong near-surface winds and melts along the ice edge south of the polar front, an important upwelling region. Here, it adds freshwater to the surface ocean, lowers the sea-water density, and possibly reduces upwelling by increasing the stratification. Consequently, this redistribution of freshwater in time and space affects the vertical overturning circulation which is an important determinant of the ocean-atmosphere CO2 exchange and, thus, of the global climate. We investigate the Southern Ocean sea-ice ocean system using satellite observations together with simulations with a newly developed regional ocean sea-ice model on the basis of ROMS. As it is not possible yet to derive sea-ice volume transport from remote sensing data due to a lack of ice thickness data, we quantify the freshwater flux exerted by the sea ice from the model and compare it to the observed sea-ice area transport. This shows that the transport is large in the Weddell and Ross Seas where sea ice extends to its lowest latitudes. We assess the importance of sea-ice freshwater transport on the stratification and circulation by comparing this flux to the net atmospheric freshwater flux from reanalysis data and by perturbing our model simulations.

  19. Periodic stratification at the head of estuarine salt tip

    NASA Astrophysics Data System (ADS)

    Kim, Yong H.; Sanford, Lawrence; Hwang, Jin H.

    2014-05-01

    Conventionally, tidal straining has been known to induce more stratified condition during ebb in estuarine settings, i.e., strain-induced periodic stratification (SIPS). As opposed to the traditional tidal straining concept, observation data from the upperreach of Chesapeake Bay demonstrate that the water column is more stratified during flood than ebb, which results in condensed suspended sediment concentration near the bed during flood. In order to assess the stability of stratified flow, a composite Froude number is estimated for the outputs from an idealized 2-dimensional vertical numerical simulation. The results show theconsistency with the conventional tidal straining in case of relatively stronger density-induced bottom flow (e.g., Normal Periodic Stratification,NPS). However, the opposite case, i.e., stratified flow during flood, is observed when freshwater flow is relatively stronger in the upper layer (i.e., Inverse Periodic Stratification, IPS). Finally, this study shows that a composite Froude number analysis can be a proper indicator representing thetidal variability in the mixing pattern at the head of estuarine salt tips.

  20. Effects of enhanced stratification on equatorward dynamo wave propagation

    SciTech Connect

    Käpylä, Petri J.; Mantere, Maarit J.; Cole, Elizabeth; Warnecke, Jörn; Brandenburg, Axel

    2013-11-20

    We present results from simulations of rotating magnetized turbulent convection in spherical wedge geometry representing parts of the latitudinal and longitudinal extents of a star. Here we consider a set of runs for which the density stratification is varied, keeping the Reynolds and Coriolis numbers at similar values. In the case of weak stratification, we find quasi-steady dynamo solutions for moderate rotation and oscillatory ones with poleward migration of activity belts for more rapid rotation. For stronger stratification, the growth rate tends to become smaller. Furthermore, a transition from quasi-steady to oscillatory dynamos is found as the Coriolis number is increased, but now there is an equatorward migrating branch near the equator. The breakpoint where this happens corresponds to a rotation rate that is about three to seven times the solar value. The phase relation of the magnetic field is such that the toroidal field lags behind the radial field by about π/2, which can be explained by an oscillatory α{sup 2} dynamo caused by the sign change of the α-effect about the equator. We test the domain size dependence of our results for a rapidly rotating run with equatorward migration by varying the longitudinal extent of our wedge. The energy of the axisymmetric mean magnetic field decreases as the domain size increases and we find that an m = 1 mode is excited for a full 2π azimuthal extent, reminiscent of the field configurations deduced from observations of rapidly rotating late-type stars.

  1. On electron bunching and stratification of glow discharges

    SciTech Connect

    Golubovskii, Yuri B.; Kolobov, Vladimir I.; Nekuchaev, Vladimir O.

    2013-10-15

    Plasma stratification and excitation of ionization waves is one of the fundamental problems in gas discharge physics. Significant progress in this field is associated with the name of Lev Tsendin. He advocated the need for the kinetic approach to this problem contrary to the traditional hydrodynamic approach, introduced the idea of electron bunching in spatially periodic electric fields, and developed a theory of kinetic resonances for analysis of moving striations in rare gases. The present paper shows how Tsendin's ideas have been further developed and applied for understanding the nature of the well-known S-, P-, and R-striations observed in glow discharges of inert gases at low pressures and currents. We review numerical solutions of a Fokker-Planck kinetic equation in spatially periodic electric fields under the effects of elastic and inelastic collisions of electrons with atoms. We illustrate the formation of kinetic resonances at specific field periods for different shapes of injected Electron Distribution Functions (EDF). Computer simulations illustrate how self-organization of the EDFs occurs under nonlocal conditions and how Gaussian-like peaks moving along resonance trajectories are formed in a certain range of discharge conditions. The calculated EDFs agree well with the experimentally measured EDFs for the S, P, and R striations in noble gases. We discuss how kinetic resonances affect dispersion characteristics of moving striations and mention some non-linear effects associated with glow discharge stratification. We propose further studies of stratification phenomena combining physical kinetics and non-linear physics.

  2. Global warming prolongs the thermal stratification of dimictic lake Mondsee.

    NASA Astrophysics Data System (ADS)

    Blatterer, Hubert; Luger, Martin

    2013-04-01

    The pre-alpine Lake Mondsee is situated at the northern margin of the European Alps (47° 49´N, 13° 24´E) in the Salzkammergut lake district of Upper Austria at a sea level of 481 m. The lake has a surface area of 14,21 km² and a maximum water depth of 68 m (volume is 500 Mio m³ and theoretical water retention time is 1,8 years). Sediment samples confirm oligotrophic conditions as historical reference status of the lake. From 1970 to 1985 the lake suffered from severe eutrophication leading to cyanobacterial blooms (Planctothrix rubescens). Reduction of nutrient load in the course of improved sewage treatment resulted in re-oligotrophication from 1985 to about 2000. Currently, lake Mondsee is assessed mesotrophic and the biological quality elements "phytoplankton" and "macrophytes" classify the lake in the "moderate ecological status". According to the Water Framework Directive, a key initiative throughout the EU, the aim is to improve water quality and reach the "good ecological status". Temperature data of the Lake have been measured since the 30ies of the last century in varying intervals. In the present study (1991 - 2009) water temperature measured at the deepest point of the lake shows an increase in average surface temperature (0 - 5 m) of about 2 °C over the last two decades. The increase is less pronounced in deeper water layers and almost not visible below 15 m depth. Due to global change and rising temperatures stratification is starting earlier in the season and is prolonged from formerly end of November to the middle or even end of December. Thus, between 1999 and 2011 in several years the stratification period was extended for 5 weeks. During stratification oxygen depletion occurs in the depth of lakes and prolonged stratification results in increased areas of oxygen depletion. The oxygen concentration controls the phosphorus release of lake sediments. Therefore prolonged stratification results in increased internal phosphorus load of the lake

  3. Risk.

    PubMed

    Cole, Stephen R; Hudgens, Michael G; Brookhart, M Alan; Westreich, Daniel

    2015-02-15

    The epidemiologist primarily studies transitions between states of health and disease. The purpose of the present article is to define a foundational parameter for such studies, namely risk. We begin simply and build to the setting in which there is more than 1 event type (i.e., competing risks or competing events), as well as more than 1 treatment or exposure level of interest. In the presence of competing events, the risks are a set of counterfactual cumulative incidence functions for each treatment. These risks can be depicted visually and summarized numerically. We use an example from the study of human immunodeficiency virus to illustrate concepts. PMID:25660080

  4. Fundamental Interactions in Gasoline Compression Ignition Engines with Fuel Stratification

    NASA Astrophysics Data System (ADS)

    Wolk, Benjamin Matthew

    Transportation accounted for 28% of the total U.S. energy demand in 2011, with 93% of U.S. transportation energy coming from petroleum. The large impact of the transportation sector on global climate change necessitates more-efficient, cleaner-burning internal combustion engine operating strategies. One such strategy that has received substantial research attention in the last decade is Homogeneous Charge Compression Ignition (HCCI). Although the efficiency and emissions benefits of HCCI are well established, practical limits on the operating range of HCCI engines have inhibited their application in consumer vehicles. One such limit is at high load, where the pressure rise rate in the combustion chamber becomes excessively large. Fuel stratification is a potential strategy for reducing the maximum pressure rise rate in HCCI engines. The aim is to introduce reactivity gradients through fuel stratification to promote sequential auto-ignition rather than a bulk-ignition, as in the homogeneous case. A gasoline-fueled compression ignition engine with fuel stratification is termed a Gasoline Compression Ignition (GCI) engine. Although a reasonable amount of experimental research has been performed for fuel stratification in GCI engines, a clear understanding of how the fundamental in-cylinder processes of fuel spray evaporation, mixing, and heat release contribute to the observed phenomena is lacking. Of particular interest is gasoline's pressure sensitive low-temperature chemistry and how it impacts the sequential auto-ignition of the stratified charge. In order to computationally study GCI with fuel stratification using three-dimensional computational fluid dynamics (CFD) and chemical kinetics, two reduced mechanisms have been developed. The reduced mechanisms were developed from a large, detailed mechanism with about 1400 species for a 4-component gasoline surrogate. The two versions of the reduced mechanism developed in this work are: (1) a 96-species version and (2

  5. Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

    NASA Astrophysics Data System (ADS)

    Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

    2016-04-01

    Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

  6. Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia.

    PubMed

    Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G; Radich, Jerald P; Brümmendorf, Tim H; Schuppert, Andreas

    2016-01-01

    Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34(+) similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients' disease history within chronic phase (CP) and significantly separates "early" from "late" CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis. PMID:27048866

  7. Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

    PubMed Central

    Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

    2016-01-01

    Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis. PMID:27048866

  8. Stratification Pattern of Static and Scale-Invariant Dynamic Measures of Heartbeat Fluctuations Across Sleep Stages in Young and Elderly

    PubMed Central

    Schmitt, Daniel T.; Stein, Phyllis K.; Ivanov, Plamen Ch.

    2010-01-01

    Cardiac dynamics exhibit complex variability characterized by scale-invariant and nonlinear temporal organization related to the mechanism of neuroautonomic control, which changes with physiologic states and pathologic conditions. Changes in sleep regulation during sleep stages are also related to fluctuations in autonomic nervous activity. However, the interaction between sleep regulation and cardiac autonomic control remains not well understood. Even less is known how this interaction changes with age, as aspects of both cardiac dynamics and sleep regulation differ in healthy elderly compared to young subjects. We hypothesize that because of the neuroautonomic responsiveness in young subjects, fractal and nonlinear features of cardiac dynamics exhibit a pronounced stratification pattern across sleep stages, while in elderly these features will remain unchanged due to age-related loss of cardiac variability and decline of neuroautonomic responsiveness. We analyze the variability and the temporal fractal organization of heartbeat fluctuations across sleep stages in both young and elderly. We find that independent linear and nonlinear measures of cardiac control consistently exhibit the same ordering in their values across sleep stages, forming a robust stratification pattern. Despite changes in sleep architecture and reduced heart rate variability in elderly subjects, this stratification surprisingly does not break down with advanced age. Moreover, the difference between sleep stages for some linear, fractal, and nonlinear measures exceeds the difference between young and elderly, suggesting that the effect of sleep regulation on cardiac dynamics is significantly stronger than the effect of healthy aging. Quantifying changes in this stratification pattern may provide insights into how alterations in sleep regulation contribute to increased cardiac risk. PMID:19203874

  9. Development and validation of a clinical score for prognosis stratification in patients requiring antiretroviral therapy in sub-Saharan Africa: a prospective open cohort study

    PubMed Central

    Gerardo, Rivero; Dayana, Pérez

    2011-01-01

    Background Mortality rates among patients initiating antiretroviral therapy (ART) in sub-Saharan Africa continue high. Also HIV treatment services from the region are affronting the challenges of been attending more patients than never. In this scenario, there are no integrated scoring systems capable of an adequate risk identification/ prognostic stratification among patients requiring ART; in order of optimize actual programmes outcomes. Several independent risk factors at baseline are associated with a poor prognosis after ART initiation. These include: male sex, low body mass index, anemia, low CD4 count and stage-4 WHO disease. The aim of this research was evaluate prospectively a new scoring system composed by these factors. Methods An open cohort study was conducted in 1769 patients from May 2008 to December 2010 at two HIV clinics of Zimbabwe. A new clinical model (MASIB score) was applied at ART initiation and patients were followed for 4 months. After that, validation characteristics of the score were examined. Results Patients selected in this cohort exhibited similar baseline characteristics that the patients selected in previous cohorts from the region. Overall performance for mortality prediction of MASIB score was accurate, as reflected by the Brier score test result 0.084 (95%CI: 0.080–0.088). Calibration was adequate taking in consideration a p>0.05 in the Hosmer Lemeshow test and discrimination was also good (Area Under Curve: 0.915, 95%CI: 0,901– 0,928). Conclusion The new model developed exhibited adequate validation characteristics supporting the clinical use. Further evaluations of this model in others scenarios from the sub-Saharan region are needed. PMID:22187587

  10. Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer.

    PubMed

    Green, Andrew R; Soria, D; Powe, D G; Nolan, C C; Aleskandarany, M; Szász, M A; Tőkés, A M; Ball, G R; Garibaldi, J M; Rakha, E A; Kulka, J; Ellis, I O

    2016-05-01

    The Nottingham prognostic index plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification for breast cancer superior to the traditional NPI. This study aimed to determine prognostic capability of the NPI+ in predicting risk of development of distant disease. A well-characterised series of 1073 primary early-stage BC cases treated in Nottingham and 251 cases from Budapest were immunohistochemically assessed for cytokeratin (Ck)5/6, Ck18, EGFR, oestrogen receptor (ER), progesterone receptor, HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class and prognostic scores were assigned using individual algorithms for each biological class incorporating clinicopathologic parameters and investigated in terms of prediction of distant metastases-free survival (MFS). The NPI+ identified distinct prognostic groups (PG) within each molecular class which were predictive of MFS providing improved patient outcome stratification superior to the traditional NPI. NPI+ PGs, between series, were comparable in predicting patient outcome between series in luminal A, basal p53 altered and HER2+/ER+ (p > 0.01) tumours. The low-risk groups were similarly validated in luminal B, luminal N, basal p53 normal tumours (p > 0.01). Due to small patient numbers the remaining PGs could not be validated. NPI+ was additionally able to predict a higher risk of metastases at certain distant sites. This study may indicate the NPI+ as a useful tool in predicting the risk of metastases. The NPI+ provides accurate risk stratification allowing improved individualised clinical decision making for breast cancer. PMID:27116185

  11. Stratification and Tdal Mixing in the Cretaceous Western Interior Seaway

    NASA Astrophysics Data System (ADS)

    Allison, P. A.; Hill, J.; Jordan, N.; Avdis, A.; Markwick, P. J.; Lunt, D. J.

    2013-12-01

    Most of the organic carbon preserved in the marine sedimentary lithosphere was deposited in shallow epicontinental seas. Understanding the processes which affected productivity and preservation of this organic matter impacts upon our understanding of the ancient carbon cycle, paleobiodiversity and hydrocarbon resource formation. The epicontinental seas of the geological past were vast, typically shallow and lack suitably scaled modern analogues. A key question is the extent to which these water-bodies were stratified or mixed and how this has affected productivity and preservation. Modern coastal seas such as the North Sea become seasonally stratified in summer but are mixed at the coasts through the interaction of the tidal wave with the seabed. The stratified deeper water is separated from the mixed coastal shallows by a front. Modern fronts are associated with elevated productivity in the frontal region with potential for preservation in stratified areas. Herein we use a range of modelling tools to evaluate the development of seasonal stratification, tidal mixing and tidal fronts in the Cretaceous Western Interior Seaway (WIS) of North America. The paleogeographies (supplied by Getech) used for this work are underpinned by extensive geological databases and based on an in-house plate model. Paleobathymetric reconstructions utilize geological observations (seismic, lithofacies, fossils) for the shelf and a combination of geological data and age-depth relationships for areas underpinned by oceanic crust. A low resolution coupled atmosphere-ocean general circulation model (HADCM3) was used to evaluate the development of seasonal stratification. Fluidity-ICOM, an unstructured FE model was used to quantify the development of tidal mixing and tidal fronts and GOTM, a 1D vertical ocean model was used to evaluate the impact of a suite of parameters (salinity, temperature, depth and atmospheric forcing) on water-body mixing. HADCM3 results show that the seaway was

  12. Laboratory Experiments on Core Merging and Stratification After Giant Impacts

    NASA Astrophysics Data System (ADS)

    Landeau, M.; Olson, P.; Deguen, R.; Hirsh, B.

    2015-12-01

    The fluid dynamics of core merging after giant impacts in the late stages of accretion provides constraints on metal-silicate equilibration, core stratification, and early magnetic field generation. The energy released during giant impacts, such as those thought to have formed Earth's Moon and the crustal dichotomy on Mars, likely resulted in melting of the impactor and much or all of the protoplanet's mantle. Under these conditions, the liquid core of the impactor migrates through a fully-liquid magma ocean, and merges with the protoplanet's core. Unlike the laminar flow in numerical simulations, liquid impact experiments can produce turbulence, as expected during core formation. We present experiments on liquid blobs of variable density released into another liquid consisting of two immiscible layers, representing the magma ocean and protocore, respectively. The released liquid is denser than the upper layer, immiscible in the upper layer, and miscible in the lower layer. With a shallow upper layer, the relevant regime for giant impacts, a turbulent cloud of released and upper liquids penetrates into the lower layer, collapses and spreads along the interface between the upper and lower layers. This behavior contrasts with the laminar core merging observed in impact simulations or the classical iron rain scenario, and suggests that metal-silicate chemical equilibration extends inside the protocore. Experimental scalings for low-density releases predict that compositional stratification of the core is likely in the aftermath of planet formation, and the stratified layer detected by seismology at the top of Earth's core is compatible with a moon-forming impact. By implication, the early core dynamo had to overcome compositional stratification to initiate.

  13. Evidence for ground-water stratification near Yucca Mountain, Nevada

    USGS Publications Warehouse

    Futa, K.; Marshall, B.D.; Peterman, Z.E.

    2006-01-01

    Major- and trace-element concentrations and strontium isotope ratios (strontium-87/strontium-86) in samples of ground water potentially can be useful in delineating flow paths in the complex ground-water system in the vicinity of Yucca Mountain, Nevada. Water samples were collected from boreholes to characterize the lateral and vertical variability in the composition of water in the saturated zone. Discrete sampling of water-producing intervals in the saturated zone includes isolating borehole sections with packers and extracting pore water from core obtained by sonic drilling. Chemical and isotopic stratification was identified in the saturated zone beneath southern Fortymile Wash.

  14. Stratification parameters and dispersion of internal solitary waves

    NASA Astrophysics Data System (ADS)

    Perevalova, E. G.; Makarenko, N. I.

    2016-06-01

    A theoretical model of internal solitary waves of large amplitude in a weakly stratified fluid is considered. It is assumed that the background density profile depends linearly or exponentially on the fluid depth. It is demonstrated that inverse problem on determining fine-scale structure of the density profile by a known curve of amplitude dispersion is reduced to solving a linear Fredholm integral equation of the first kind having special form of the kernel. The one-to-one correspondence between the density coefficient and the dispersion function is established in the case of analytical stratification.

  15. Risk prediction models for hepatocellular carcinoma in different populations

    PubMed Central

    Ma, Xiao; Yang, Yang; Tu, Hong; Gao, Jing; Tan, Yu-Ting; Zheng, Jia-Li; Bray, Freddie; Xiang, Yong-Bing

    2016-01-01

    Hepatocellular carcinoma (HCC) is a malignant disease with limited therapeutic options due to its aggressive progression. It places heavy burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well. PMID:27199512

  16. Risk prediction models for hepatocellular carcinoma in different populations.

    PubMed

    Ma, Xiao; Yang, Yang; Tu, Hong; Gao, Jing; Tan, Yu-Ting; Zheng, Jia-Li; Bray, Freddie; Xiang, Yong-Bing

    2016-04-01

    Hepatocellular carcinoma (HCC) is a malignant disease with limited therapeutic options due to its aggressive progression. It places heavy burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well. PMID:27199512

  17. Numerical Study of Wake Vortex Behavior in Turbulent Domains with Ambient Stratification

    NASA Technical Reports Server (NTRS)

    Switzer, George F.; Proctor, Fred H.

    2000-01-01

    A three-dimensional large eddy simulation model is used to investigate the sensitivity of ambient stratification with turbulence on the behavior of aircraft wake vortices. Modeled ambient turbulence levels range from very weak to moderate, and stratification levels range from strongly stable to unstable. The results of profound significance from this study are: 1) very little sensitivity between vortex linking time and the level of stratification, 2) the mean vortex separation remained nearly constant regardless of stratification and turbulence (at least prior to linking), 3) the wake vortices did not rise regardless of the level of stratification, and 4) for very strong stratification, the vortex stopped descending and quickly dissipated even before vortex linking could occur. These results are supported by experimental data and are contrary to conclusions from other numerical studies that assume laminar flow and/or relatively-low Reynolds numbers.

  18. An Improved Model of Cryogenic Propellant Stratification in a Rotating, Reduced Gravity Environment

    NASA Technical Reports Server (NTRS)

    Oliveira, Justin; Kirk, Daniel R.; Schallhorn, Paul A.; Piquero, Jorge L.; Campbell, Mike; Chase, Sukhdeep

    2007-01-01

    This paper builds on a series of analytical literature models used to predict thermal stratification within rocket propellant tanks. The primary contribution to the literature is to add the effect of tank rotation and to demonstrate the influence of rotation on stratification times and temperatures. This work also looks levels of thermal stratification for generic propellant tanks (cylindrical shapes) over a parametric range of upper-stage coast times, heating levels, rotation rates, and gravity levels.

  19. Accuracy of heritability estimations in presence of hidden population stratification.

    PubMed

    Dandine-Roulland, Claire; Bellenguez, Céline; Debette, Stéphanie; Amouyel, Philippe; Génin, Emmanuelle; Perdry, Hervé

    2016-01-01

    The heritability of a trait is the proportion of its variance explained by genetic factors; it has historically been estimated using familial data. However, new methods have appeared for estimating heritabilities using genomewide data from unrelated individuals. A drawback of this strategy is that population stratification can bias the estimates. Indeed, an environmental factor associated with the phenotype may differ among population subgroups. This factor being associated both with the phenotype and the genetic variation in the population would be a confounder. A common solution consists in adjusting on the first Principal Components (PCs) of the genomic data. We study this procedure on simulated data and on 6000 individuals from the Three-City Study. We analyse the geographical coordinates of the birth cities, which are not genetically determined, but the heritability of which should be overestimated due to population stratification. We also analyse various anthropometric traits. The procedure fails to correct the bias in geographical coordinates heritability estimates. The heritability estimates of the anthropometric traits are affected by the inclusion of the first PC, but not by the following PCs, contrarily to geographical coordinates. We recommend to be cautious with heritability estimates obtained from a large population. PMID:27220488

  20. Space Shuttle Upgrade Liquid Oxygen Tank Thermal Stratification

    NASA Technical Reports Server (NTRS)

    Tunc, Gokturk; Wagner, Howard; Bayazitoglu, Yildiz

    2001-01-01

    In 1997, NASA initiated a study of a liquid oxygen and ethanol orbital maneuvering and reaction control system for space shuttle upgrades as well as other reusable launch vehicle applications. The pressure-fed system uses sub-cooled liquid oxygen at 2413.2 KPa (350 psia) stored passively using insulation. Thermal stratification builds up while the space shuttle is docked at the international space station. The venting from the space shuttle's liquid oxygen tank is not desired during this 96-hr time period. Once the shuttle undocks from the space station there could be a pressure collapse in the liquid oxygen tank caused by fluid mixing due to the thruster fU"ings . The thermal stratification and resulting pressure rise in the tank were examined by a computational fluid dynamic model. Since the heat transfer from the pressurant gas to the liquid will result in a decrease in tank pressure the final pressure after the 96 hours will be significantly less when the tank is pressurized with ambient temperature helium. Therefore, using helium at ambient temperature to pressurize the tank is preferred to pressurizing the tank with helium at the liquid oxygen temperature. The higher helium temperature will also result in less mass of helium to pressurize the tank.

  1. Stratification of gallstone fragments: the key to more effective fragmentation.

    PubMed

    Alderfer, J T; Laufer, I; Wisniewski, F; Malet, P F

    1992-04-01

    During previous experiments with in vitro fragmentation in a simulated gallbladder, we noticed that stone fragments tended to stratify with the dust and smaller fragments settled to the dependent portion, while the larger fragments settled on top. We reviewed the oral cholecystogram (OCG) of 10 patients examined 6 months following gallstone lithotripsy. In all cases with adequate visualization of stone fragments, the stratification phenomenon was observed. We hypothesized that adjusting the shock wave focus to target on these large fragments would improve the efficiency of fragmentation. To test this hypothesis, we fragmented three matched pairs of gallstones in vitro. For each pair, the stones were removed from the same gallbladder and the stone weights of the two stones were within 10%. The smaller member of each pair was fragmented using the "old method" with the focus on the fragment line. The larger stone was fragmented with the "new method" with the focus in the acoustic shadow deep to the echogenic line caused by the dust and small fragments in the dependent portion. The distribution of fragments was analyzed by passing the fragments through a series of filters. With the new method of targeting, the proportion of fragments less than 1.5 mm was doubled while the fragments greater than 5 mm were eliminated. The new method of targeting, taking into account the stratification of stone fragments, produces more effective fragmentation and should lead to more rapid clearance of fragments from the gallbladder. PMID:10149180

  2. Accuracy of heritability estimations in presence of hidden population stratification

    PubMed Central

    Dandine-Roulland, Claire; Bellenguez, Céline; Debette, Stéphanie; Amouyel, Philippe; Génin, Emmanuelle; Perdry, Hervé

    2016-01-01

    The heritability of a trait is the proportion of its variance explained by genetic factors; it has historically been estimated using familial data. However, new methods have appeared for estimating heritabilities using genomewide data from unrelated individuals. A drawback of this strategy is that population stratification can bias the estimates. Indeed, an environmental factor associated with the phenotype may differ among population subgroups. This factor being associated both with the phenotype and the genetic variation in the population would be a confounder. A common solution consists in adjusting on the first Principal Components (PCs) of the genomic data. We study this procedure on simulated data and on 6000 individuals from the Three-City Study. We analyse the geographical coordinates of the birth cities, which are not genetically determined, but the heritability of which should be overestimated due to population stratification. We also analyse various anthropometric traits. The procedure fails to correct the bias in geographical coordinates heritability estimates. The heritability estimates of the anthropometric traits are affected by the inclusion of the first PC, but not by the following PCs, contrarily to geographical coordinates. We recommend to be cautious with heritability estimates obtained from a large population. PMID:27220488

  3. Increasing the Knowledge of Stratification in Shallow Coastal Environments

    NASA Astrophysics Data System (ADS)

    Ojo, T.; Bonner, J.; Hodges, B.; Maidment, D.; Montagna, P.; Minsker, B.

    2006-12-01

    A testbed has been established using Corpus Christi Bay as an environmental field facility to study the phenomenon of hypoxia that has been observed to develop at certain periods during the year. Stratification affects vertical turbulent mixing of heat, momentum and mass (or constituents) within the water column, in turn influencing the transport of material. The mixing threshold is dependent on the value of the Richardson Number, Ri with inhibition due to stratification occurring at low values (< 0.25) and complete vertical mixing occurring at high values (> 0.25) of Ri. Corpus Christi Bay with average depth of ~3 m is the largest among a system of five bays has been known to stratify due to inflows of hypersaline water (up to 50 psu) from adjoining bays, the Laguna Madre and Oso Bay. Laguna Madre is separated from the Gulf of Mexico by a barrier island and becomes hypersaline because of the imbalance between inflow of freshwater and bay evaporation. Hypersalinity also occurs in Oso Bay due to anthropogenic forcing from a power plant that draws 400 MGD of cooling water from the upper Laguna Madre, discharging waste water into Oso Bay. Several wastewater treatment plants also discharge directly into Oso Bay or its tributary streams. The objective of this study is to develop a methodology for prescribing a set of parameters required for modeling and characterization of hypoxia in this shallow wind-driven bay. The extent to which Ri is dependent on external forcing at the surface boundary was measured using our fully instrumented sensor platforms. Each sensor platform includes sensors for synchronic near-surface meteorological (wind velocity, barometric pressure, air temperature) and water column oceanographic (current, water temperature, conductivity, particle size distribution, particulate concentration, dissolved oxygen, nutrient) variables. These were measured using fixed and mobile vertical profiling sensor platforms. A 2D hydrodynamic model was initially

  4. NNLOPS accurate associated HW production

    NASA Astrophysics Data System (ADS)

    Astill, William; Bizon, Wojciech; Re, Emanuele; Zanderighi, Giulia

    2016-06-01

    We present a next-to-next-to-leading order accurate description of associated HW production consistently matched to a parton shower. The method is based on reweighting events obtained with the HW plus one jet NLO accurate calculation implemented in POWHEG, extended with the MiNLO procedure, to reproduce NNLO accurate Born distributions. Since the Born kinematics is more complex than the cases treated before, we use a parametrization of the Collins-Soper angles to reduce the number of variables required for the reweighting. We present phenomenological results at 13 TeV, with cuts suggested by the Higgs Cross section Working Group.

  5. How to accurately bypass damage

    PubMed Central

    Broyde, Suse; Patel, Dinshaw J.

    2016-01-01

    Ultraviolet radiation can cause cancer through DNA damage — specifically, by linking adjacent thymine bases. Crystal structures show how the enzyme DNA polymerase η accurately bypasses such lesions, offering protection. PMID:20577203

  6. Accurate Evaluation of Quantum Integrals

    NASA Technical Reports Server (NTRS)

    Galant, David C.; Goorvitch, D.

    1994-01-01

    Combining an appropriate finite difference method with Richardson's extrapolation results in a simple, highly accurate numerical method for solving a Schr\\"{o}dinger's equation. Important results are that error estimates are provided, and that one can extrapolate expectation values rather than the wavefunctions to obtain highly accurate expectation values. We discuss the eigenvalues, the error growth in repeated Richardson's extrapolation, and show that the expectation values calculated on a crude mesh can be extrapolated to obtain expectation values of high accuracy.

  7. Identifiability, stratification and minimum variance estimation of causal effects.

    PubMed

    Tong, Xingwei; Zheng, Zhongguo; Geng, Zhi

    2005-10-15

    The weakest sufficient condition for the identifiability of causal effects is the weakly ignorable treatment assignment, which implies that potential responses are independent of treatment assignment in each fine subpopulation stratified by a covariate. In this paper, we expand the independence that holds in fine subpopulations to the case that the independence may also hold in several coarse subpopulations, each of which consists of several fine subpopulations and may have overlaps with other coarse subpopulations. We first show that the identifiability of causal effects occurs if and only if the coarse subpopulations partition the whole population. We then propose a principle, called minimum variance principle, which says that the estimator possessing the minimum variance is preferred, in dealing with the stratification and the estimation of the causal effects. The simulation results with the detail programming and a practical example demonstrate that it is a feasible and reasonable way to achieve our goals. PMID:16149123

  8. Stratification in Al and Cu foils exploded in vacuum

    SciTech Connect

    Baksht, R. B.; Rousskikh, A. G.; Zhigalin, A. S.; Artyomov, A. P.; Oreshkin, V. I.

    2015-10-15

    An experiment with exploding foils was carried out at a current density of 0.7 × 10{sup 8} A/cm{sup 2} through the foil with a current density rise rate of about 10{sup 15} A/cm{sup 2} s. To record the strata arising during the foil explosions, a two-frame radiographic system was used that allowed tracing the dynamics of strata formation within one shot. The original striation wavelength was 20–26 μm. It was observed that as the energy deposition to a foil stopped, the striation wavelength increased at a rate of ∼(5–9) × 10{sup 3} cm/s. It is supposed that the most probable reason for the stratification is the thermal instability that develops due to an increase in the resistivity of the metal with temperature.

  9. Stratification-Based Outlier Detection over the Deep Web

    PubMed Central

    Xian, Xuefeng; Zhao, Pengpeng; Sheng, Victor S.; Fang, Ligang; Gu, Caidong; Yang, Yuanfeng; Cui, Zhiming

    2016-01-01

    For many applications, finding rare instances or outliers can be more interesting than finding common patterns. Existing work in outlier detection never considers the context of deep web. In this paper, we argue that, for many scenarios, it is more meaningful to detect outliers over deep web. In the context of deep web, users must submit queries through a query interface to retrieve corresponding data. Therefore, traditional data mining methods cannot be directly applied. The primary contribution of this paper is to develop a new data mining method for outlier detection over deep web. In our approach, the query space of a deep web data source is stratified based on a pilot sample. Neighborhood sampling and uncertainty sampling are developed in this paper with the goal of improving recall and precision based on stratification. Finally, a careful performance evaluation of our algorithm confirms that our approach can effectively detect outliers in deep web. PMID:27313603

  10. Career on the Move: Geography, Stratification, and Scientific Impact

    PubMed Central

    Deville, Pierre; Wang, Dashun; Sinatra, Roberta; Song, Chaoming; Blondel, Vincent D.; Barabási, Albert-László

    2014-01-01

    Changing institutions is an integral part of an academic life. Yet little is known about the mobility patterns of scientists at an institutional level and how these career choices affect scientific outcomes. Here, we examine over 420,000 papers, to track the affiliation information of individual scientists, allowing us to reconstruct their career trajectories over decades. We find that career movements are not only temporally and spatially localized, but also characterized by a high degree of stratification in institutional ranking. When cross-group movement occurs, we find that while going from elite to lower-rank institutions on average associates with modest decrease in scientific performance, transitioning into elite institutions does not result in subsequent performance gain. These results offer empirical evidence on institutional level career choices and movements and have potential implications for science policy. PMID:24759743

  11. Physiological stratification in electricity-producing biofilms of Geobacter sulfurreducens.

    PubMed

    Schrott, Germán David; Ordoñez, María Victoria; Robuschi, Luciana; Busalmen, Juan Pablo

    2014-02-01

    The elucidation of mechanisms and limitations in electrode respiration by electroactive biofilms is significant for the development of rapidly emerging clean energy production and wastewater treatment technologies. In Geobacter sulfurreducens biofilms, the controlling steps in current production are thought to be the metabolic activity of cells, but still remain to be determined. By quantifying the DNA, RNA, and protein content during the long-term growth of biofilms on polarized graphite electrodes, we show in this work that current production becomes independent of DNA accumulation immediately after a maximal current is achieved. Indeed, the mean respiratory rate of biofilms rapidly decreases after this point, which indicates the progressive accumulation of cells that do not contribute to current production or contribute to a negligible extent. These results support the occurrence of physiological stratification within biofilms as a consequence of respiratory limitations imposed by limited biofilm conductivity. PMID:24307451

  12. School Stratification in New and Established Latino Destinations

    PubMed Central

    Dondero, Molly; Muller, Chandra

    2012-01-01

    The growth and geographic diversification of the school-age Latino population suggest that schools in areas that previously had very few Latinos now serve many of these students. This study uses the 1999-2000 Schools and Staffing Survey and the Education Longitudinal Study of 2002 to compare public high schools in new and established Latino destinations. We examine school composition, school quality indicators, instructional resources and access to advanced math courses. We find that schools in new destinations display more favorable educational contexts according to a number of measures, but offer fewer linguistic support services than schools in established destinations. We also find evidence of a within-school Latino-white gap in advanced math course taking in new destinations, suggesting greater educational stratification within schools in those areas. PMID:24503908

  13. Thermodynamics of inequalities: From precariousness to economic stratification

    NASA Astrophysics Data System (ADS)

    Smerlak, Matteo

    2016-01-01

    Growing economic inequalities are observed in several countries throughout the world. Following Pareto, the power-law structure of these inequalities has been the subject of much theoretical and empirical work. But their nonequilibrium dynamics, e.g. after a policy change, remains incompletely understood. Here we introduce a thermodynamical theory of inequalities based on the analogy between economic stratification and statistical entropy. Within this framework we identify the combination of upward mobility with precariousness as a fundamental driver of inequality. We formalize this statement by a "second-law" inequality displaying upward mobility and precariousness as thermodynamic conjugate variables. We estimate the time scale for the "relaxation" of the wealth distribution after a sudden change of the after-tax return on capital. Our method can be generalized to gain insight into the dynamics of inequalities in any Markovian model of socioeconomic interactions.

  14. Experimental verification of scaling parameters for thermal stratification

    NASA Astrophysics Data System (ADS)

    Ji, H.-C.; Schwartz, S. H.; Lovrich, T. N.; Hochstein, J. I.; Holmes, L. A.

    1992-09-01

    A study to determine important dimensionless parameters associated with thermal stratification of a heated container of liquid, and the pressure history of its vapor, was performed. Analysis of the governing equations identified the modified Grashoff number, the modified Fourier number, and the interface number as the dominant dimensionless parameters associated with this process. A test program designed to verify the validity of these scaling parameters was executed. The quality of scaling was checked by comparing the dimensionless pressures and temperatures for scaled pairs of tests. Results indicate that the bulk liquid temperature, the surface temperature of the liquid, and the tank pressure can be scaled with the three dimensionless parameters. Some deviations were found in the detailed temperature profiles between the scaled pairs of tests.

  15. Consensus and stratification in the affective meaning of human sociality

    PubMed Central

    Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

    2014-01-01

    We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification. PMID:24843121

  16. Stratification in Al and Cu foils exploded in vacuum

    NASA Astrophysics Data System (ADS)

    Baksht, R. B.; Rousskikh, A. G.; Zhigalin, A. S.; Oreshkin, V. I.; Artyomov, A. P.

    2015-10-01

    An experiment with exploding foils was carried out at a current density of 0.7 × 108 A/cm2 through the foil with a current density rise rate of about 1015 A/cm2 s. To record the strata arising during the foil explosions, a two-frame radiographic system was used that allowed tracing the dynamics of strata formation within one shot. The original striation wavelength was 20-26 μm. It was observed that as the energy deposition to a foil stopped, the striation wavelength increased at a rate of ˜(5-9) × 103 cm/s. It is supposed that the most probable reason for the stratification is the thermal instability that develops due to an increase in the resistivity of the metal with temperature.

  17. Stratification and enumeration of Boolean functions by canalizing depth

    NASA Astrophysics Data System (ADS)

    He, Qijun; Macauley, Matthew

    2016-01-01

    Boolean network models have gained popularity in computational systems biology over the last dozen years. Many of these networks use canalizing Boolean functions, which has led to increased interest in the study of these functions. The canalizing depth of a function describes how many canalizing variables can be recursively "picked off", until a non-canalizing function remains. In this paper, we show how every Boolean function has a unique algebraic form involving extended monomial layers and a well-defined core polynomial. This generalizes recent work on the algebraic structure of nested canalizing functions, and it yields a stratification of all Boolean functions by their canalizing depth. As a result, we obtain closed formulas for the number of n-variable Boolean functions with depth k, which simultaneously generalizes enumeration formulas for canalizing, and nested canalizing functions.

  18. Stratification-Based Outlier Detection over the Deep Web.

    PubMed

    Xian, Xuefeng; Zhao, Pengpeng; Sheng, Victor S; Fang, Ligang; Gu, Caidong; Yang, Yuanfeng; Cui, Zhiming

    2016-01-01

    For many applications, finding rare instances or outliers can be more interesting than finding common patterns. Existing work in outlier detection never considers the context of deep web. In this paper, we argue that, for many scenarios, it is more meaningful to detect outliers over deep web. In the context of deep web, users must submit queries through a query interface to retrieve corresponding data. Therefore, traditional data mining methods cannot be directly applied. The primary contribution of this paper is to develop a new data mining method for outlier detection over deep web. In our approach, the query space of a deep web data source is stratified based on a pilot sample. Neighborhood sampling and uncertainty sampling are developed in this paper with the goal of improving recall and precision based on stratification. Finally, a careful performance evaluation of our algorithm confirms that our approach can effectively detect outliers in deep web. PMID:27313603

  19. Thermal Stratification Effects on Flow Over a Generic Urban Canopy

    NASA Astrophysics Data System (ADS)

    Boppana, V. B. L.; Xie, Z.-T.; Castro, I. P.

    2014-10-01

    The influence of local surface heating and cooling on flow over urban-like roughness is investigated using large-eddy simulations. By adjusting the incoming or outgoing heat flux from the ground surface, various degrees of local thermal stratification, represented by a Richardson number , were attained. Drag and heat transfer coefficients, turbulence structure, integral length scales, and the strength of quadrant events that contribute to momentum and heat fluxes were obtained and are compared with locally stable, neutral and unstable flows. With increasing , or equivalently as the flow characteristics change from local thermal instability to stability, a gradual decline in the drag and heat transfer coefficients is observed. These values are found to be fairly independent of the type of thermal boundary condition (constant heat flux or constant temperature) and domain size. The maps of anisotropy invariants showed that for the values of considered, turbulence structures are almost the same in shape for neutral and unstable cases but differ slightly from those in the stable case. The degree of anisotropy is found to decrease as increases from to 2.5. Compared to the neutral case, the integral length scales are shortened in the streamwise and vertical direction by ground cooling, but enhanced in the vertical direction with ground heating. Quadrant analysis showed that an increase in floor heating increases the strength of ejections above the canopy. However, the contributions of updrafts or downdrafts to the heat flux are found not to be significantly influenced by the type of local thermal stratification for the values of considered. From the octant analysis, the transport mechanisms of momentum and heat above the canopy are found to be very similar in both locally unstable and stable flows.

  20. How-to-Do-It: A Practical Method for Teaching Seed Stratification.

    ERIC Educational Resources Information Center

    Englert, Karen M.; Shontz, Nancy N.

    1989-01-01

    Described is a laboratory procedure for teaching seed stratification. Materials, methods, results, and applicability of the experiment are explained. Diagrams showing the percent of total germination as a function of stratification time and the germination rate of stratified seeds are included. (RT)

  1. Marginal Mean Weighting through Stratification: Adjustment for Selection Bias in Multilevel Data

    ERIC Educational Resources Information Center

    Hong, Guanglei

    2010-01-01

    Defining causal effects as comparisons between marginal population means, this article introduces marginal mean weighting through stratification (MMW-S) to adjust for selection bias in multilevel educational data. The article formally shows the inherent connections among the MMW-S method, propensity score stratification, and…

  2. Stratification of soil organic carbon and its impact on environmental quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stratification of soil organic C occurs when plant residues are placed at the soil surface and disturbance of soil is minimized. Vertical stratification of soil organic C within the soil profile is common in forests, grasslands, and managed agroecosystems using conservation tillage, cover cropping,...

  3. Unraveling the Stratification of an Iron-Oxidizing Microbial Mat by Metatranscriptomics

    PubMed Central

    Quaiser, Achim; Bodi, Xavier; Dufresne, Alexis; Naquin, Delphine; Francez, André-Jean; Dheilly, Alexandra; Coudouel, Sophie; Pedrot, Mathieu; Vandenkoornhuyse, Philippe

    2014-01-01

    A metatranscriptomic approach was used to study community gene expression in a naturally occurring iron-rich microbial mat. Total microbial community RNA was reversely transcribed and sequenced by pyrosequencing. Characterization of expressed gene sequences provided accurate and detailed information of the composition of the transcriptionally active community and revealed phylogenetic and functional stratifications within the mat. Comparison of 16S rRNA reads and delineation of OTUs showed significantly lower values of metatranscriptomic-based richness and diversity in the upper parts of the mat than in the deeper regions. Taxonomic affiliation of rRNA sequences and mRNA genome recruitments indicated that iron-oxidizing bacteria affiliated to the genus Leptothrix, dominated the community in the upper layers of the mat. Surprisingly, type I methanotrophs contributed to the majority of the sequences in the deep layers of the mat. Analysis of mRNA expression patterns showed that genes encoding the three subunits of the particulate methane monooxygenase (pmoCAB) were the most highly expressed in our dataset. These results provide strong hints that iron-oxidation and methane-oxidation occur simultaneously in microbial mats and that both groups of microorganisms are major players in the functioning of this ecosystem. PMID:25033299

  4. Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years.

    PubMed

    Engelhardt, Monika; Ihorst, Gabriele; Landgren, Ola; Pantic, Milena; Reinhardt, Heike; Waldschmidt, Johannes; May, Annette M; Schumacher, Martin; Kleber, Martina; Wäsch, Ralph

    2015-10-01

    Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary malignancies have also gained attention since randomized data showed associations to newer drugs. We have conducted this large registry analysis in 744 consecutive patients and analyzed: 1) frequency and onset of additional malignancies; and 2) second primary malignancy- and myeloma-specific risks. We assessed the frequency of additional malignancies in terms of host-, myeloma- and treatment-specific characteristics. To compare these risks, we estimated cumulative incidence rates for second malignancies and myeloma with Fine and Gray regression models taking into account competing risks. Additional malignancies were found in 118 patients: prior or synchronous malignancies in 63% and subsequent in 37%. Cumulative incidence rates for second malignancies were increased in IgG-myeloma and decreased in bortezomib-treated patients (P<0.05). Cumulative incidence rates for myeloma death were increased with higher stage and age, but decreased in IgG-subtypes and due to anti-myeloma treatment (P<0.05). Cytogenetics in patients acquiring second primary malignancies were predominantly favorable, suggesting that indolent myeloma and long disease latency may allow the manifestation of additional malignancies. An assessment of the Surveillance, Epidemiology, and End Result Program of the National Cancer Institute and our data with long-term follow up of 25 years confirmed a prevalence of second malignancy of 10% at 25 years, whereas death from myeloma decreased from 90% to 83%, respectively. Our important findings widen our knowledge of second malignancies and show that they are of increasing relevance as the prognosis in myeloma improves and mortality rates decrease. PMID:26160877

  5. Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years

    PubMed Central

    Engelhardt, Monika; Ihorst, Gabriele; Landgren, Ola; Pantic, Milena; Reinhardt, Heike; Waldschmidt, Johannes; May, Annette M.; Schumacher, Martin; Kleber, Martina; Wäsch, Ralph

    2015-01-01

    Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary malignancies have also gained attention since randomized data showed associations to newer drugs. We have conducted this large registry analysis in 744 consecutive patients and analyzed: 1) frequency and onset of additional malignancies; and 2) second primary malignancy- and myeloma-specific risks. We assessed the frequency of additional malignancies in terms of host-, myeloma- and treatment-specific characteristics. To compare these risks, we estimated cumulative incidence rates for second malignancies and myeloma with Fine and Gray regression models taking into account competing risks. Additional malignancies were found in 118 patients: prior or synchronous malignancies in 63% and subsequent in 37%. Cumulative incidence rates for second malignancies were increased in IgG-myeloma and decreased in bortezomib-treated patients (P<0.05). Cumulative incidence rates for myeloma death were increased with higher stage and age, but decreased in IgG-subtypes and due to anti-myeloma treatment (P<0.05). Cytogenetics in patients acquiring second primary malignancies were predominantly favorable, suggesting that indolent myeloma and long disease latency may allow the manifestation of additional malignancies. An assessment of the Surveillance, Epidemiology, and End Result Program of the National Cancer Institute and our data with long-term follow up of 25 years confirmed a prevalence of second malignancy of 10% at 25 years, whereas death from myeloma decreased from 90% to 83%, respectively. Our important findings widen our knowledge of second malignancies and show that they are of increasing relevance as the prognosis in myeloma improves and mortality rates decrease. PMID:26160877

  6. Age-Stratified Risk of Unexpected Uterine Sarcoma Following Surgery for Presumed Benign Leiomyoma

    PubMed Central

    Li, Li; Andikyan, Vaagn; Običan, Sarah G.; Cioffi, Angela; Hao, Ke; Dudley, Joel T.; Ascher-Walsh, Charles; Kasarskis, Andrew; Maki, Robert G.

    2015-01-01

    Background. Estimates of unexpected uterine sarcoma following surgery for presumed benign leiomyoma that use age-stratification are lacking. Patients and Methods. A retrospective cohort of 2,075 patients that had undergone myomectomy was evaluated to determine the case incidence of unexpected uterine sarcoma. An aggregate risk estimate was generated using a meta-analysis of similar studies plus our data. Database-derived age distributions of the incidence rates of uterine sarcoma and uterine leiomyoma surgery were used to stratify risk by age. Results. Of 2,075 patients in our retrospective cohort, 6 were diagnosed with uterine sarcoma. Our meta-analysis revealed 8 studies from 1980 to 2014. Combined with our study, 18 cases of leiomyosarcoma are reported in 10,120 patients, for an aggregate risk of 1.78 per 1,000 (95% confidence interval [CI]: 1.1–2.8) or 1 in 562. Eight cases of other uterine sarcomas were reported in 6,889 patients, for an aggregate risk of 1.16 per 1,000 (95% CI: 0.5–4.9) or 1 in 861. The summation of these risks gives an overall risk of uterine sarcoma of 2.94 per 1,000 (95% CI: 1.8–4.1) or 1 in 340. After stratification by age, we predict the risk of uterine sarcoma to range from a peak of 10.1 cases per 1,000, or 1 in 98, for patients aged 75–79 years to <1 case per 500 for patients aged <30 years. Conclusion. The risk of unexpected uterine sarcoma varies significantly across age groups. Our age-stratified predictive model should be incorporated to more accurately counsel patients and to assist in providing guidelines for the surgical technique for leiomyoma. PMID:25765878

  7. How to Think About Risk in Myeloma.

    PubMed

    Krishnan, Amrita

    2016-08-01

    An integral part of myeloma therapy is risk stratification of newly diagnosed patients. This method involves a combination of staging and genetic risk assessment. Although survival has dramatically improved for patients with genetically defined, standard-risk myeloma, those with high-risk disease remain a therapeutic challenge. Current treatment approaches might include the use of combination therapy for induction and maintenance. Future approaches are expected to involve drugs that are "risk agnostic," such as monoclonal antibodies and immunotherapy. PMID:27521310

  8. Abundances determined using Si ii and Si iii in B-type stars: evidence for stratification

    NASA Astrophysics Data System (ADS)

    Bailey, J. D.; Landstreet, J. D.

    2013-03-01

    Context. It is becoming clear that determination of the abundance of Si using lines of Si ii and Si iii can lead to quite discordant results in mid to late B-type stars. The difference between the Si abundances derived from the two ion states can exceed one dex in some cases. Aims: We have carried out a study intended to clarify which kinds of B stars exhibit this discrepancy, to try to identify regularities in the phenomenon, and to explore possible explanations such as abundance stratification by comparing models to observed spectra. Methods: We used spectra from the ESPaDOnS spectropolarimeter and FEROS spectrograph, supplemented with spectra from the ESO and ELODIE archives, of magnetic Bp, HgMn, and normal B-type stars ranging in effective temperature from about 10 500 to 15 000 K. Using these spectra, we derived abundances using the spectrum synthesis program zeeman, which can take the influence of magnetic fields into account. For each star, accurate abundances of Si ii, Si iii, Ti, Cr, and Fe were derived from two separate ~100 Å windows. Si ii abundances were deduced from multiple lines, and Si iii abundances were found using λλ 4552, 4567, and 4574. Results: All magnetic Bp stars in our sample show a discordance between the derived abundances of the first and second ions of silicon, with the latter being between 0.6-1.7 dex higher. The same behaviour is observed in the non-magnetic stars but to a much smaller extent: Si iii is enhanced by between 0.3-0.8 dex compared to Si ii. We do not detect the discrepancy in three stars, HD 22 136 (normal), HD 57 608 (HgMn) and HD 27 295 (HgMn); these are the only stars in our sample for which the microturbulence parameter is significantly different from zero, and which therefore probably have convection occurring in their atmospheres. Conclusions: We find that vertical stratification of silicon in the atmospheres of B-type stars may provide an explanation of this phenomenon, but our detailed stratification models

  9. One-Dimensional Analysis of Thermal Stratification in AHTR and SFR Coolant Pools

    SciTech Connect

    Haihua Zhao; Per F. Peterson

    2007-10-01

    Thermal stratification phenomena are very common in pool type reactor systems, such as the liquid-salt cooled Advanced High Temperature Reactor (AHTR) and liquid-metal cooled fast reactor systems such as the Sodium Fast Reactor (SFR). It is important to accurately predict the temperature and density distributions both for design optimation and accident analysis. Current major reactor system analysis codes such as RELAP5 (for LWR’s, and recently extended to analyze high temperature reactors), TRAC (for LWR’s), and SASSYS (for liquid metal fast reactors) only provide lumped-volume based models which can only give very approximate results and can only handle simple cases with one mixing source. While 2-D or 3-D CFD methods can be used to analyze simple configurations, these methods require very fine grid resolution to resolve thin substructures such as jets and wall boundaries, yet such fine grid resolution is difficult or impossible to provide for studying the reactor response to transients due to computational expense. Therefore, new methods are needed to support design optimization and safety analysis of Generation IV pool type reactor systems. Previous scaling has shown that stratified mixing processes in large stably stratified enclosures can be described using one-dimensional differential equations, with the vertical transport by free and wall jets modeled using standard integral techniques. This allows very large reductions in computational effort compared to three-dimensional numerical modeling of turbulent mixing in large enclosures. The BMIX++ (Berkeley mechanistic MIXing code in C++) code was originally developed at UC Berkeley to implement such ideas. This code solves mixing and heat transfer problems in stably stratified enclosures. The code uses a Lagrangian approach to solve 1-D transient governing equations for the ambient fluid and uses analytical or 1-D integral models to compute substructures. By including liquid salt properties, BMIX++ code is

  10. Risk scoring for prediction of acute cardiac complications from imbalanced clinical data.

    PubMed

    Liu, Nan; Koh, Zhi Xiong; Chua, Eric Chern-Pin; Tan, Licia Mei-Ling; Lin, Zhiping; Mirza, Bilal; Ong, Marcus Eng Hock

    2014-11-01

    Fast and accurate risk stratification is essential in the emergency department (ED) as it allows clinicians to identify chest pain patients who are at high risk of cardiac complications and require intensive monitoring and early intervention. In this paper, we present a novel intelligent scoring system using heart rate variability, 12-lead electrocardiogram (ECG), and vital signs where a hybrid sampling-based ensemble learning strategy is proposed to handle data imbalance. The experiments were conducted on a dataset consisting of 564 chest pain patients recruited at the ED of a tertiary hospital. The proposed ensemble-based scoring system was compared with established scoring methods such as the modified early warning score and the thrombolysis in myocardial infarction score, and showed its effectiveness in predicting acute cardiac complications within 72 h in terms of the receiver operation characteristic analysis. PMID:25375686

  11. A modeling study of the physical processes affecting the development of seasonal hypoxia over the inner Louisiana-Texas shelf: Circulation and stratification

    NASA Astrophysics Data System (ADS)

    Wang, Lixia; Justić, Dubravko

    2009-06-01

    The physical processes affecting the development of seasonal hypoxia over the Louisiana-Texas shelf were examined using a high-resolution, three-dimensional, unstructured-grid, Finite Volume Coastal Ocean Model (FVCOM). The model was forced with the observed freshwater fluxes from the Mississippi and Atchafalaya Rivers, surface winds, heat fluxes, tides and offshore conditions. The simulations were carried out over a six-month period, from April to September 2002, and the model performance was evaluated against several independent series of observations that included tidal gauge data, Acoustic Doppler Current Profiler (ADCP) data, shipboard measurements of temperature and salinity, vertical salinity and sigma-t profiles, and satellite imagery. The model accurately described the offshore circulation mode generated over the Louisiana-Texas shelf by the westerly winds during summer months, as well as the prevalent westward flow along the coast caused by the easterly winds during the rest of the study period. The seasonal cycle of stratification also was well represented by the model. During 2002, the stratification was initiated in early spring and subsequently enhanced by the intensity and phasing of riverine freshwater discharges. Strong stratification persisted throughout the summer and was finally broken down in September by tropical storms. The model simulations also revealed a quasi-permanent anticyclonic gyre in the Louisiana Bight region formed by the rotational transformation of the Mississippi River plume, whose existence during 2002 was supported by the satellite imagery and ADCP current measurements. Model simulations support the conclusion that local wind forcing and buoyancy flux resulting from riverine freshwater discharges were the dominant mechanisms affecting the circulation and stratification over the inner Louisiana-Texas shelf.

  12. Methane oxidation in Saanich Inlet during summer stratification

    NASA Technical Reports Server (NTRS)

    Ward, B. B.; Kilpatrick, K. A.; Wopat, A. E.; Minnich, E. C.; Lidstrom, M. E.

    1989-01-01

    Saanich Inlet, British Columbia, an fjord on the southeast coast of Vancouver Island, typically stratifies in summer, leading to the formation of an oxic-anoxic interface in the water column and accumulation of methane in the deep water. The results of methane concentration measurements in the water column of the inlet at various times throughout the summer months in 1983 are presented. Methane gradients and calculated diffusive fluxes across the oxic-anoxic interface increased as the summer progressed. Methane distribution and consumption in Saanich Inlet were studied in more detail during August 1986. At this time, a typical summer stratification with an oxic-anoxic interface around 140 m was present. At the interface, steep gradients in nutrient concentrations, bacterial abundance and methane concentration were observed. Methane oxidation was detected in the aerobic surface waters and in the anaerobic deep layer, but highest rates occurred in a narrow layer at the oxic-anoxic interface. Estimated methane oxidation rates were suffcient to consume 100 percent of the methane provided by diffusive flux from the anoxic layer. Methane oxidation is thus a mechanism whereby atmospheric flux from anoxic waters is minimized.

  13. USING BIOBIN TO EXPLORE RARE VARIANT POPULATION STRATIFICATION*

    PubMed Central

    Moore, Carrie B.; Wallace, John R.; Frase, Alex T.; Pendergrass, Sarah A.; Ritchie, Marylyn D.

    2013-01-01

    Rare variants (RVs) will likely explain additional heritability of many common complex diseases; however, the natural frequencies of rare variation across and between human populations are largely unknown. We have developed a powerful, flexible collapsing method called BioBin that utilizes prior biological knowledge using multiple publicly available database sources to direct analyses. Variants can be collapsed according to functional regions, evolutionary conserved regions, regulatory regions, genes, and/or pathways without the need for external files. We conducted an extensive comparison of rare variant burden differences (MAF < 0.03) between two ancestry groups from 1000 Genomes Project data, Yoruba (YRI) and European descent (CEU) individuals. We found that 56.86% of gene bins, 72.73% of intergenic bins, 69.45% of pathway bins, 32.36% of ORegAnno annotated bins, and 9.10% of evolutionary conserved regions (shared with primates) have statistically significant differences in RV burden. Ongoing efforts include examining additional regional characteristics using regulatory regions and protein binding domains. Our results show interesting variant differences between two ancestral populations and demonstrate that population stratification is a pervasive concern for sequence analyses. PMID:23424138

  14. Turbulence in the East China Sea: The summertime stratification

    NASA Astrophysics Data System (ADS)

    Lozovatsky, Iossif; Lee, Jae-Hak; Fernando, H. J. S.; Kang, Sok Kuh; Jinadasa, S. U. P.

    2015-03-01

    A series of 134 microstructure profiles were taken in the central East China Sea from a drifting ship, covering more than 12 miles over the sloping bottom. The water depth z varied in the range 52-62 m; the tidal elevation of semidiurnal component was ±1 m. Prior to the onset of 25 h drift, a hydrographic section consisting of 9 stations, 15 miles apart, was taken in the area. A shallow mixed surface layer (SL) underlain by a diurnal pycnocline (z < 13 m), a sharp thermohalocline (13 < z < 30 m), and about 20 m tall bottom boundary layer (BBL) were the main features of summertime stratification. The splitting of upper pycnocline by a warmer, saltier intrusion led to the generation of turbulent patches at the lower, but not at the upper, density interface of this water body, suggesting asymmetry of mixing across the intrusion. In a limited range of the normalized squared buoyancy frequency, 2(N2/N02>)-3, where ɛm=4×10-6 W/kg and N0=5×10-3 s-1. Measurements in the sharp pycnocline and in lesser-stratified transitional layers between the pycnocline and the SL and BBL show that the cumulative distribution functions CDF(log10ɛ) can be modeled either by the generalized extreme value (GEV) distribution or the lognormal distribution.

  15. Flow modulation based control of granular stratification in heaps

    NASA Astrophysics Data System (ADS)

    Umbanhowar, Paul B.; Fan, Yi; McDonald, David; Ottino, Julio M.; Lueptow, Richard M.

    2013-11-01

    Gravity driven flows of initially mixed granular media composed of non-monodisperse particles spontaneously segregate for a wide range of particle and flow parameters. For heaps of size-bidisperse particles formed in the quasi-two-dimensional geometry of a vertical Hele-Shaw cell, segregation is in the form of stratified layers of large and small particle-rich bands that are nominally parallel to the free surface of the heap. Stratification occurs at low fill rates where flow down the heap manifests as a series of intermittent and irregularly sized avalanches. This non-steady flow causes variation in stratum thickness and streamwise extent. In this talk we describe how temporal modulation of the fill rate can generate ordered strata at high fill rates. In particular, we show how, for a duty cycle variation of the flow rate, the modulation parameters determine the wavelength and streamwise extent of the layers. We explain our results in terms of the dependence of the dynamic repose angle on flow rate. Finally we describe how the upstream extent of the strata increases with decreasing gap width and is related to the jamming probability of the large particles. Y.F. was funded by The Dow Chemical Company.

  16. Clinical application of a novel automatic algorithm for actigraphy-based activity and rest period identification to accurately determine awake and asleep ambulatory blood pressure parameters and cardiovascular risk.

    PubMed

    Crespo, Cristina; Fernández, José R; Aboy, Mateo; Mojón, Artemio

    2013-03-01

    This paper reports the results of a study designed to determine whether there are statistically significant differences between the values of ambulatory blood pressure monitoring (ABPM) parameters obtained using different methods-fixed schedule, diary, and automatic algorithm based on actigraphy-of defining the main activity and rest periods, and to determine the clinical relevance of such differences. We studied 233 patients (98 men/135 women), 61.29 ± .83 yrs of age (mean ± SD). Statistical methods were used to measure agreement in the diagnosis and classification of subjects within the context of ABPM and cardiovascular disease risk assessment. The results show that there are statistically significant differences both at the group and individual levels. Those at the individual level have clinically significant implications, as they can result in a different classification, and, therefore, different diagnosis and treatment for individual subjects. The use of an automatic algorithm based on actigraphy can lead to better individual treatment by correcting the accuracy problems associated with the fixed schedule on patients whose actual activity/rest routine differs from the fixed schedule assumed, and it also overcomes the limitations and reliability issues associated with the use of diaries. PMID:23130607

  17. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    RAZ scoring is a simple, accurate and inexpensive screening technique for cardiomyopathy. Although HF QRS ECG is highly sensitive for cardiomyopathy, its specificity may be compromised in patients with cardiac pathologies other than cardiomyopathy, such as uncomplicated coronary artery disease or multiple coronary disease risk factors. Further studies are required to determine whether HF QRS might be useful for monitoring cardiomyopathy severity or the efficacy of therapy in a longitudinal fashion.

  18. Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation.

    PubMed Central

    Auguste, Peter; Tsertsvadze, Alexander; Pink, Joshua; Court, Rachel; Seedat, Farah; Gurung, Tara; Freeman, Karoline; Taylor-Phillips, Sian; Walker, Clare; Madan, Jason; Kandala, Ngianga-Bakwin; Clarke, Aileen; Sutcliffe, Paul

    2016-01-01

    BACKGROUND Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) [(Zopf 1883) Lehmann and Neumann 1896], is a major cause of morbidity and mortality. Nearly one-third of the world's population is infected with MTB; TB has an annual incidence of 9 million new cases and each year causes 2 million deaths worldwide. OBJECTIVES To investigate the clinical effectiveness and cost-effectiveness of screening tests [interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs)] in latent tuberculosis infection (LTBI) diagnosis to support National Institute for Health and Care Excellence (NICE) guideline development for three population groups: children, immunocompromised people and those who have recently arrived in the UK from high-incidence countries. All of these groups are at higher risk of progression from LTBI to active TB. DATA SOURCES Electronic databases including MEDLINE, EMBASE, The Cochrane Library and Current Controlled Trials were searched from December 2009 up to December 2014. REVIEW METHODS English-language studies evaluating the comparative effectiveness of commercially available tests used for identifying LTBI in children, immunocompromised people and recent arrivals to the UK were eligible. Interventions were IGRAs [QuantiFERON(®)-TB Gold (QFT-G), QuantiFERON(®)-TB Gold-In-Tube (QFT-GIT) (Cellestis/Qiagen, Carnegie, VA, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK)]. The comparator was TST 5 mm or 10 mm alone or with an IGRA. Two independent reviewers screened all identified records and undertook a quality assessment and data synthesis. A de novo model, structured in two stages, was developed to compare the cost-effectiveness of diagnostic strategies. RESULTS In total, 6687 records were screened, of which 53 unique studies were included (a further 37 studies were identified from a previous NICE guideline). The majority of the included studies compared the strength of association for the QFT-GIT/G IGRA with the TST (5

  19. Development of thermal stratification and destratification scaling concepts. Volume 1: Definition of thermal stratification scaling parameters and experimental investigations

    NASA Technical Reports Server (NTRS)

    Lovrich, T. N.; Schwartz, S. H.

    1975-01-01

    The dimensionless parameters associated with the thermal stratification and pressure history of a heated container of liquid and its vapor were examined. The Modified Grashof number, the Fourier number, and an Interface number were parameterized using a single test liquid, Freon 113. Cylindrical test tanks with spherical dome end caps were built. Blanket heaters covered the tanks and thermocouples monitored the temperatures of the liquid, the ullage, the tank walls, and the foam insulation encapsulating the tank. A centrifuge was used for the 6 inch tank to preserve the same scaling parameter values between it and the larger tanks. Tests were conducted over a range of Gr* values and the degree of scaling was checked by comparing the dimensionless pressures and temperatures for each scaled pair of tests. Results indicate that the bulk liquid temperature, the surface temperature of the liquid, and the tank pressure can be scaled with the three dimensionless parameters. Some deviation was, however, found in the detailed temperature profiles between the scaled pairs of tests.

  20. KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification

    PubMed Central

    Tetreault, Marie-Pier; Weinblatt, Daniel; Shaverdashvili, Khvaramze; Yang, Yizeng; Katz, Jonathan P.

    2016-01-01

    Epithelial differentiation and stratification are essential for normal homeostasis, and disruption of these processes leads to both injury and cancer. The zinc-finger transciption factor KLF4 is a key driver of epithelial differentiation, yet the mechanisms and targets by which KLF4 controls differentiation are not well understood. Here, we define WNT5A, a non-canonical Wnt ligand implicated in epithelial differentiation, repair, and cancer, as a direct transcriptional target that is activated by KLF4 in squamous epithelial cells. Further, we demonstrate functionally that WNT5A mediates KLF4 control of epithelial differentiation and stratification, as treatment of keratinocytes with WNT5A rescues defective epithelial stratification resulting from KLF4 loss. Finally, we show that the small GTPase CDC42 is regulated by KLF4 in a WNT5A dependent manner. As such, we delineate a novel pathway for epithelial differentiation and stratification and define potential therapeutic targets for epithelial diseases. PMID:27184424

  1. Investigation of Thermal Stratification by Direct Contact Condensation in a Suppression Pool

    NASA Astrophysics Data System (ADS)

    Okamoto, Koji; Song, Daehun; Erkan, Nejdet

    2014-11-01

    Thermal stratification in the suppression pool of Boiling Water Reactor were investigated using simple slab-type experimental facilities. The steam direct condensation causes the vibration of bubble interface, resulting in the mixing enhancement at the nozzle. Using the bubble motion model, the Richardson number had been estimated which is a ratio of buoyancy to interface fluctuation momentum. The thermal stratification occurrence had been strong relation to the Richardson number. The flow pattern inside the chamber had also affected by the Richardson number. The flow pattern were measured by PIV. The velocity distribution were compared with the numerical simulation, showing the good agreement. In small Ri, i.e., lower fluctuation condition, the thermal stratification does occur. Thus, the momentum caused by the direct condensation determined the occurrence of the thermal stratification.

  2. Accommodating Missingness When Assessing Surrogacy Via Principal Stratification

    PubMed Central

    Elliott, Michael R.; Li, Yun; Taylor, Jeremy M.G.

    2014-01-01

    Background When an outcome of interest in a clinical trial is late-occurring or difficult to obtain, surrogate markers can extract information about the effect of the treatment on the outcome of interest. Understanding associations between the causal effect of treatment on the outcome and the causal effect of treatment on the surrogate is critical to understanding the value of a surrogate from a clinical perspective. Purpose Traditional regression approaches to determine the proportion of the treatment effect explained by surrogate markers suffer from several shortcomings: they can be unstable, and can lie outside of the 0–1 range. Further, they do not account for the fact that surrogate measures are obtained post-randomization, and thus the surrogate-outcome relationship may be subject to unmeasured confounding. Methods to avoid these problem are of key importance. Methods Frangakis C, Rubin DM. Principal stratification in causal inference. Biometrics 2002; 58:21–9 suggested assessing the causal effect of treatment within pre-randomization “principal strata” defined by the counterfactual joint distribution of the surrogate marker under the different treatment arms, with the proportion of the overall outcome causal effect attributable to subjects for whom the treatment affects the proposed surrogate as the key measure of interest. Li Y, Taylor JMG, Elliott MR. Bayesian approach to surrogacy assessment using principal stratification in clinical trials. Biometrics 2010; 66:523–31 developed this “principal surrogacy” approach for dichotomous markers and outcomes, utilizing Bayesian methods that accommodated non-identifiability in the model parameters. Because the surrogate marker is typically observed early, outcome data is often missing. Here we extend Li, Taylor, and Elliott to accommodate missing data in the observable final outcome under ignorable and non-ignorable settings. We also allow for the possibility that missingness has a counterfactual

  3. Ethiopian population dermatoglyphic study reveals linguistic stratification of diversity.

    PubMed

    Yohannes, Seile; Bekele, Endashaw

    2015-01-01

    also to reveal the stratification mechanism in play. PMID:26042929

  4. Thermal and Compositional Stratification of the Inner Core

    NASA Astrophysics Data System (ADS)

    Labrosse, S.

    2014-12-01

    The improvements on the knowledge of the seismic structure of the inner core and the complexities thereby revealed ask for a dynamical origin. Sub-solidus convection was one of the early suggestions to explain the seismic anisotropy but requires an unstable density gradient either from thermal or compositional origin, or both. Temperature and composition profiles in the inner core are computed using a unidimensional model of core evolution including diffusion in the inner core and fractional crystallisation at the the inner core boundary (ICB). The thermal conductivity of the core has been recently revised upwardly and, moreover, found increasing with depth. Values of the heat flow across the core mantle boundary (CMB) sufficient to maintain convection in the whole outer core are not sufficient to make the temperature in the inner core super-isentropic and therefore prone to thermal instability. An unreasonably high CMB heat flow is necessary to this end. The compositional stratification results from a competition of the increase of the concentration in O and S in the outer core with inner core growth, which makes the inner core concentration also increase, and of the decrease of the liquidus which makes the partition coefficient decrease as well as the concentration of light elements in the solid. While the latter (destabilizing) effect dominates at small inner core sizes, the former takes over for a large inner core. The turnover point is encountered for an inner core about half its current size in the case of S but much larger for the case of O. The combined thermal and compositional buoyancy is stabilizing and solid-state convection in the inner core appears unlikely, unless an early double-diffusive instability can set in.

  5. The Effect of Mesoscale Eddies On Oceanic Stratification

    NASA Astrophysics Data System (ADS)

    Vallis, G. K.; Henning, C. C.

    Understanding the structure of the subtropical thermocline is an important, indeed classical, problem in dynamical oceanography. Many models have fallen into two camps -- diffusive theories, following Robinson and Stommel, and advective theo- ries, following Welander. More recently it has been shown that, at least in the absence of mesoscale eddies, the subtropical thermocline consists of an advective upper part (a 'ventilated thermocline'), with a diffusive base -- that is, the lower part of the main thermocline is an internal boundary layer. The thermocline in the Southern Ocean is a rather different beast, because the lack of meridional boundaries means that the gyre circulation is largely absent and such classical theories do not directly apply. Further- more, it has been suggested that the dynamics of the Southern Ocean might greatly influence the thermocline worldwide. However, these theories are not complete. Among the most egregious omissions is that of the potential effect of mesoscale eddies, and here we explore that problem. We integrate to equilibrium a wind- and buoyancy-driven eddy-resolving primitive- equations ocean model, both in an idealized basin and in a circumpolar channel. We find that mesoscale eddies do have a significant quantitative affect on the structure of the thermocline. In the subtropics, the signature of the two-thermocline model (an advective upper thermocline and a diffusive base) remains, even in the presence of vigorous eddying activity, whereas in the circumpolar channel the eddies appear to be a dominant process determining the stratification. We discuss the dynamics and thermodynamics of these flows, and present some simple theoretical ideas to partially explain some of our results.

  6. Network stratification analysis for identifying function-specific network layers.

    PubMed

    Zhang, Chuanchao; Wang, Jiguang; Zhang, Chao; Liu, Juan; Xu, Dong; Chen, Luonan

    2016-04-22

    A major challenge of systems biology is to capture the rewiring of biological functions (e.g. signaling pathways) in a molecular network. To address this problem, we proposed a novel computational framework, namely network stratification analysis (NetSA), to stratify the whole biological network into various function-specific network layers corresponding to particular functions (e.g. KEGG pathways), which transform the network analysis from the gene level to the functional level by integrating expression data, the gene/protein network and gene ontology information altogether. The application of NetSA in yeast and its comparison with a traditional network-partition both suggest that NetSA can more effectively reveal functional implications of network rewiring and extract significant phenotype-related biological processes. Furthermore, for time-series or stage-wise data, the function-specific network layer obtained by NetSA is also shown to be able to characterize the disease progression in a dynamic manner. In particular, when applying NetSA to hepatocellular carcinoma and type 1 diabetes, we can derive functional spectra regarding the progression of the disease, and capture active biological functions (i.e. active pathways) in different disease stages. The additional comparison between NetSA and SPIA illustrates again that NetSA could discover more complete biological functions during disease progression. Overall, NetSA provides a general framework to stratify a network into various layers of function-specific sub-networks, which can not only analyze a biological network on the functional level but also investigate gene rewiring patterns in biological processes. PMID:26879865

  7. Malaria stratification, climate, and epidemic early warning in Eritrea.

    PubMed

    Ceccato, Pietro; Ghebremeskel, Tewolde; Jaiteh, Malanding; Graves, Patricia M; Levy, Marc; Ghebreselassie, Shashu; Ogbamariam, Andom; Barnston, Anthony G; Bell, Michael; del Corral, John; Connor, Stephen J; Fesseha, Issac; Brantly, Eugene P; Thomson, Madeleine C

    2007-12-01

    Eritrea has a successful malaria control program, but it is still susceptible to devastating malaria epidemics. Monthly data on clinical malaria cases from 242 health facilities in 58 subzobas (districts) of Eritrea from 1996 to 2003 were used in a novel stratification process using principal component analysis and nonhierarchical clustering to define five areas with distinct malaria intensity and seasonality patterns, to guide future interventions and development of an epidemic early warning system. Relationships between monthly clinical malaria incidence by subzoba and monthly climate data from several sources, and with seasonal climate forecasts, were investigated. Remotely sensed climate data were averaged over the same subzoba geographic administrative units as the malaria cases. Although correlation was good between malaria anomalies and actual rainfall from ground stations (lagged by 2 months), the stations did not have sufficiently even coverage to be widely useful. Satellite derived rainfall from the Climate Prediction Center Merged Analysis of Precipitation was correlated with malaria incidence anomalies, with a lead time of 2-3 months. NDVI anomalies were highly correlated with malaria incidence anomalies, particularly in the semi-arid north of the country and along the northern Red Sea coast, which is a highly epidemic-prone area. Eritrea has 2 distinct rainy seasons in different parts of the country. The seasonal forecasting skill from Global Circulation Models for the June/July/August season was low except for the Eastern border. For the coastal October/November/December season, forecasting skill was good only during the 1997-1998 El Niño event. For epidemic control, shorter-range warning based on remotely sensed rainfall estimates and an enhanced epidemic early-detection system based on data derived for this study are needed. PMID:18165476

  8. Enhanced stratification in the lower Chesapeake Bay following northeasterly winds

    NASA Astrophysics Data System (ADS)

    Valle-Levinson, Arnoldo; Miller, Jerry L.; Wheless, Glen H.

    1998-11-01

    Density data from a lower Chesapeake Bay transect obtained after two northeasterly wind events were used to describe the effects of these events on the density field in the lower estuary. The first northeaster occurred in early August 1995 and the second northeaster was related to the passage of hurricane Felix off the lower bay in mid-August 1995. The latter northeaster prolonged a period of persistent winds from the N and NE that began in early August and caused storm surges of similar magnitude to the former northeaster. The salinity fields observed after the early August event suggested encroachment of coastal waters into the lower bay as reflected by high salinities throughout the transect. Two days after weakening of the winds related to Felix, the density distribution across the lower bay showed strongly stratified conditions. This behavior suggested that the inflow of coastal water into the lower bay and the wind mixing related to Felix combined to produce a vertically uniform density gradient perpendicular to the bay entrance that relaxed after the winds weakened. This weakening of the winds coincided with neap tidal currents, which were not energetic enough to maintain vertical homogeneity and must have allowed the self-adjustment of the density gradient and the seaward advection of relatively buoyant waters near the surface. These mechanisms were illustrated with simplified numerical experiments. The findings of this study are used to propose the hypothesis that, in general, enhanced stratification and flushing in the lower bay will ensue the relaxation of a northeasterly wind event, provided that this relaxation coincides with a weak friction regime, i.e., neap tides.

  9. Evidence for gammacerane as an indicator of water column stratification

    NASA Technical Reports Server (NTRS)

    Sinninghe Damste, J. S.; Kenig, F.; Koopmans, M. P.; Koster, J.; Schouten, S.; Hayes, J. M.; de Leeuw, J. W.

    1995-01-01

    A new route for the formation of gammacerane from tetrahymanol is proposed; in addition to dehydration and hydrogenation, sulphurisation and early C-S cleavage are shown to be important in the pathway of formation, especially in marine sediments. Evidence is twofold. First, relatively large amounts of the gammacerane skeleton are sequestered in S-rich macromolecular aggregates formed by natural sulphurisation of functionalised lipids. Selective cleavage of polysulphide linkages with MeLi/MeI led to formation of 3-methylthiogammacerane, indicating that the gammacerane skeleton is primarily bound via sulphur at position 3, consistent with the idea that tetrahymanol (or the corresponding ketone) is the precursor for gammacerane. Second, upon mild artificial maturation of two sediments using hydrous pyrolysis, gammacerane is released from S-rich macromolecular aggregates by cleavage of the relatively weak C-S bonds. The stable carbon isotopic compositions of gammacerane and lipids derived from primary producers and green sulphur bacteria in both the Miocene Gessoso-solfifera and Upper Jurassic Allgau Formations indicate that gammacerane is derived from bacterivorous ciliates which were partially feeding on green sulphur bacteria. This demonstrates that anaerobic ciliates living at or below the chemocline are important sources for gammacerane, consistent with the fact that ciliates only biosynthesize tetrahymanol if their diet is deprived of sterols. This leads to the conclusion that gammacerane is an indicator for water column stratification, which solves two current enigmas in gammacerane geochemistry. Firstly, it explains why gammacerane is often found in sediments deposited under hypersaline conditions but is not necessarily restricted to this type of deposits. Secondly, it explains why lacustrine deposits may contain abundant gammacerane since most lakes in the temperate climatic zones are stratified during summer.

  10. Stratification effects on the plankton of the subtropical Canary Current

    NASA Astrophysics Data System (ADS)

    Schmoker, Claire; Hernández-León, Santiago

    2013-12-01

    The Canary Current has experienced a progressive warming and a decrease in productivity over the last decades. In order to study the effect of stratification in these waters, we conducted a weekly sampling at one station (28°04‧N 15°21‧E) located ∼3 nmi offshore in the 100 m isobath, at the edge of the island shelf of Gran Canaria Island (Canary Islands). The sampling was performed over two and a half years, from January 2005 to June 2007, covering the most productive season in subtropical waters, the so-called late winter bloom, three times. The variables measured were temperature, chlorophyll a (Chl a), heterotrophic and autotrophic prokaryotes, pico-, nano-, micro- and mesozooplankton biomass. During 2005, the mixing of the water column started in January, while in 2007 the mixing period was delayed one month. Between years, temperature showed an increase of 0.5 °C, and Chl a decreased to half of the initial concentration (from ∼0.50 to ∼0.25 mg Chl a m-3). Autotrophic picoplankton and heterotrophic prokaryotes decreased between 2005 and 2007. However, neither nanoflagellates nor microplankton showed this decrease. The mesozooplankton biomass outburst lasted for three months in 2005, two in 2006, and only one month in 2007. Contrary to previously hypothesized size relationships, we did not observe an increase in the contribution of autotrophic picoplankton to total phytoplankton during periods of higher stability of the water column, but the opposite. We explain this surprising finding by possible top-down effects and by the success of motile morphotypes of algae (i.e., small dinoflagellates) under stable, nutrient-limited, conditions. Overall, the results suggest that small inter-annual differences in temperature, resulting in a tendency towards more stratified waters, give rise to important changes in the structure of the pelagic ecosystem in subtropical waters through a combination of bottom-up and top-down effects.

  11. Biomarker-based prognostic stratification of young adult glioblastoma.

    PubMed

    Zhang, Rui-Qi; Shi, Zhifeng; Chen, Hong; Chung, Nellie Yuk-Fei; Yin, Zi; Li, Kay Ka-Wai; Chan, Danny Tat-Ming; Poon, Wai Sang; Wu, Jinsong; Zhou, Liangfu; Chan, Aden Ka-Yin; Mao, Ying; Ng, Ho-Keung

    2016-01-26

    While the predominant elderly and the pediatric glioblastomas have been extensively investigated, young adult glioblastomas were understudied. In this study, we sought to stratify young adult glioblastomas by BRAF, H3F3A and IDH1 mutations and examine the clinical relevance of the biomarkers. In 107 glioblastomas aged from 17 to 35 years, mutually exclusive BRAF-V600E (15%), H3F3A-K27M (15.9%), H3F3A-G34R/V (2.8%) and IDH1-R132H (16.8%) mutations were identified in over half of the cases. EGFR amplification and TERTp mutation were only detected in 3.7% and 8.4% in young adult glioblastomas, respectively. BRAF-V600E identified a clinically favorable subset of glioblastomas with younger age, frequent CDKN2A homozygous deletion, and was more amendable to surgical resection. H3F3A-K27M mutated glioblastomas were tightly associated with midline locations and showed dismal prognosis. IDH1-R132H was associated with older age and favorable outcome. Interestingly, tumors with positive PDGFRA immunohistochemical expression exhibited poorer prognosis and identified an aggressive subset of tumors among K27M mutated glioblastomas. Combining BRAF, H3F3A and IDH1 mutations allowed stratification of young adult glioblastomas into four prognostic subgroups. In summary, our study demonstrates the clinical values of stratifying young adult glioblastomas with BRAF, H3F3A and IDH1 mutations, which has important implications in refining prognostic classification of glioblastomas. PMID:26452024

  12. Biomarker-based prognostic stratification of young adult glioblastoma

    PubMed Central

    Chen, Hong; Chung, Nellie Yuk-Fei; Yin, Zi; Li, Kay Ka-Wai; Chan, Danny Tat-Ming; Poon, Wai Sang; Wu, Jinsong; Zhou, Liangfu; Chan, Aden Ka-yin; Mao, Ying; Ng, Ho-Keung

    2016-01-01

    While the predominant elderly and the pediatric glioblastomas have been extensively investigated, young adult glioblastomas were understudied. In this study, we sought to stratify young adult glioblastomas by BRAF, H3F3A and IDH1 mutations and examine the clinical relevance of the biomarkers. In 107 glioblastomas aged from 17 to 35 years, mutually exclusive BRAF-V600E (15%), H3F3A-K27M (15.9%), H3F3A-G34R/V (2.8%) and IDH1-R132H (16.8%) mutations were identified in over half of the cases. EGFR amplification and TERTp mutation were only detected in 3.7% and 8.4% in young adult glioblastomas, respectively. BRAF-V600E identified a clinically favorable subset of glioblastomas with younger age, frequent CDKN2A homozygous deletion, and was more amendable to surgical resection. H3F3A-K27M mutated glioblastomas were tightly associated with midline locations and showed dismal prognosis. IDH1-R132H was associated with older age and favorable outcome. Interestingly, tumors with positive PDGFRA immunohistochemical expression exhibited poorer prognosis and identified an aggressive subset of tumors among K27M mutated glioblastomas. Combining BRAF, H3F3A and IDH1 mutations allowed stratification of young adult glioblastomas into four prognostic subgroups. In summary, our study demonstrates the clinical values of stratifying young adult glioblastomas with BRAF, H3F3A and IDH1 mutations, which has important implications in refining prognostic classification of glioblastomas. PMID:26452024

  13. Formation of inversely graded, downstream-dipping, low-angle cross-stratification by antidunes

    SciTech Connect

    Clifton, T.R.

    1987-05-01

    Antidunes migrating upstream during aggradation produce a distinctive internal structure that results from the upstream climb of the bed form. This structure differs markedly from the upstream-dipping foresets usually ascribed to antidunes. Most studies on antidune internal structures focus on equilibrium conditions where there is no net deposition and preservation potential of structures is limited. Experiments where aggradation was induced in small coastal streams show that upstream-climbing antidunes produce low-angle, downstream-dipping, cross-stratification 1-10 mm thick. The stratification results from grain size and density segregation between the antidune trough and crest. Studies show that small, dense grains form a lag in the antidune trough while coarser, less-dense grains accumulate at the crest. The grain segregation causes inverse grading within the stratification as the antidune body and crest pass over the finer grained lag in the trough. Upstream-dipping foresets are not commonly formed by this process as there is no avalanching of grains over the bed form. Temporal variations in flow velocity may produce upstream-dipping foresets bounded by the downstream-dipping cross-stratification, but these features are subtle. The studies above suggest that antidune cross-stratification may be more common in fluvial deposits than previously thought. Deposits along the Toutle River in southern Washington show numerous examples of inversely graded, downstream-dipping, low-angle (up to 15) cross-stratification 1-5 cm thick, quite similar to antidune cross-stratification produced experimentally. Local upstream-dipping cross-stratification bounded by the downstream-dipping strata strengthens the interpretation.

  14. Numerical and experimental studies of liquid storage tank thermal stratification for a solar energy system

    SciTech Connect

    Wu, S T; Han, S M

    1980-11-01

    The results of theoretical and experimental studies of thermal stratification in liquid energy storage tanks for the performance of solar energy systems are presented. The investigation was divided into three areas: (1) Justification of the Importance of Thermal Stratification Inside the Energy Storage Tanks, (II) Development of a Simple Mathematical Model which is Compatible with Existing Solar Energy System Simulation Code, and (III) Validation of Mathematical Models by Experimental Data Obtained from Realistic Solar Energy System Operations.

  15. Near-Surface Effects of Free Atmosphere Stratification in Free Convection

    NASA Astrophysics Data System (ADS)

    Mellado, Juan Pedro; van Heerwaarden, Chiel C.; Garcia, Jade Rachele

    2016-04-01

    The effect of a linear stratification in the free atmosphere on near-surface properties in a free convective boundary layer (CBL) is investigated by means of direct numerical simulation. We consider two regimes: a neutral stratification regime, which represents a CBL that grows into a residual layer, and a strong stratification regime, which represents the equilibrium (quasi-steady) entrainment regime. We find that the mean buoyancy varies as z^{-1/3}, in agreement with classical similarity theory. However, the root-mean-square (r.m.s.) of the buoyancy fluctuation and the r.m.s. of the vertical velocity vary as z^{-0.45} and ln z, respectively, both in disagreement with theory. These scaling laws are independent of the stratification regime, but the depth over which they are valid depends on the stratification. In the strong stratification regime, this depth is about 20 to 25 % of the CBL depth instead of the commonly used 10 %, which we only observe under neutral conditions. In both regimes, the near-surface flow structure can be interpreted as a hierarchy of circulations attached to the surface. Based on this structure, we define a new near-surface layer in free convection, the plume-merging layer, that is conceptually different from the constant-flux layer. The varying depth of the plume-merging layer depending on the stratification accounts for the varying depth of validity of the scaling laws. These findings imply that the buoyancy transfer law needed in mixed-layer and single-column models is well described by the classical similarity theory, independent of the stratification in the free atmosphere, even though other near-surface properties, such as the r.m.s. of the buoyancy fluctuation and the r.m.s. of the vertical velocity, are inconsistent with that theory.

  16. Elimination of temperature stratification in a low-speed open-return wind tunnel

    NASA Astrophysics Data System (ADS)

    Cimbala, J. M.; Park, W. J.

    1989-06-01

    It is noted that temperature stratification can be a significant source of error during hot-wire measurements in low-speed, open-return wind tunnels that operate in an enclosed room. The stratification is suggested to be eliminated by resort to a thorough mixing of the air just upstream of the wind-tunnel inlet. Since the facility is equipped with adequate turbulence management, mixing can be accomplished without reduction of flow quality.

  17. Effects of water clarity on lake stratification and lake-atmosphere heat exchange

    NASA Astrophysics Data System (ADS)

    Heiskanen, Jouni J.; Mammarella, Ivan; Ojala, Anne; Stepanenko, Victor; Erkkilä, Kukka-Maaria; Miettinen, Heli; Sandström, Heidi; Eugster, Werner; Leppäranta, Matti; Järvinen, Heikki; Vesala, Timo; Nordbo, Annika

    2015-08-01

    Recent progress of including lake subroutines in numerical weather prediction (NWP) models has led to more accurate forecasts. In lake models, one essential parameter is water clarity, parameterized via the light extinction coefficient, Kd, for which a global constant value is usually used. We used direct eddy covariance fluxes and basic meteorological measurements coupled with lake water temperature and clarity measurements from a boreal lake to estimate the performance of two lake models, LAKE and FLake. These models represent two 1-D modeling frameworks broadly used in NWP. The results show that the lake models are very sensitive to changes in Kd when it is lower than 0.5 m-1. The progress of thermal stratification depended strongly on Kd. In dark-water simulations the mixed layer was shallower, longwave and turbulent heat losses higher, and therefore the average water column temperatures lower than in clear-water simulations. Thus, changes in water clarity can also affect the onset of ice cover. The more complex LAKE modeled the seasonal thermocline deepening, whereas it remained virtually constant during summer in the FLake model. Both models overestimated the surface water temperatures by about 1°C and latent heat flux by >30%, but the variations in heat storage and sensible heat flux were adequately simulated. Our results suggest that, at least for humic lakes, a lake-specific, but not time-depending, constant value for Kd can be used and that a global mapping of Kd would be most beneficial in regions with relatively clear lakes, e.g., in lakes at high altitudes.

  18. Changes in oxidative patterns during dormancy break by warm and cold stratification in seeds of an edible fruit tree

    PubMed Central

    Shalimu, Dilinuer; Sun, Jia; Baskin, Carol C.; Baskin, Jerry M.; Sun, Liwei; Liu, Yujun

    2016-01-01

    The transition from seed dormancy to germination is triggered by environmental factors, and in pomegranate (Punica granatum) seeds higher germination percentages are achieved by warm + cold stratification rather than by cold stratification alone. Our objective was to define the pattern of internal oxidative changes in pomegranate seeds as dormancy was being broken by warm + cold stratification and by cold stratification alone. Embryos isolated from seeds after 1–42 days of warm stratification, after 56 days of warm stratification + 7, 28 or 56 days of cold stratification, and after 1–84 days of cold stratification alone, were used in biochemical tests. Hydrogen peroxide (H2O2), nitric oxide (NO), proline, lipid peroxidation, protein carbonylation, and activities of the scavenging enzymes superoxide dismutase (SOD), hydrogen peroxide enzyme and peroxidase in the embryos were assessed by colorimetric methods. Our results indicated that warm + cold stratification had a stronger dormancy-breaking effect than cold stratification (85% versus 50% germination), which may be attributed to a higher yield of H2O2, NO, lipid peroxidation and protein carbonylation in warm + cold stratification. Furthermore, warm + cold stratification-induced H2O2 change led to greater changes (elevation followed by attenuation) in activities of the scavenging enzymes than that induced by cold stratification alone. These results indicated that restriction of the level of reactive oxygen species change within a positive and safe range by such enzymes promoted seed germination. In addition, a relatively strong elevation of proline during warm + cold stratification also contributed to dormancy breakage and subsequent germination. In conclusion, the strong dormancy alleviating effect of warm + cold stratification on pomegranate seeds may be attributed to the corresponding active oxidative change via H2O2, NO, proline, malondialdehyde, protein carbonylation and

  19. Changes in oxidative patterns during dormancy break by warm and cold stratification in seeds of an edible fruit tree.

    PubMed

    Shalimu, Dilinuer; Sun, Jia; Baskin, Carol C; Baskin, Jerry M; Sun, Liwei; Liu, Yujun

    2016-01-01

    The transition from seed dormancy to germination is triggered by environmental factors, and in pomegranate (Punica granatum) seeds higher germination percentages are achieved by warm + cold stratification rather than by cold stratification alone. Our objective was to define the pattern of internal oxidative changes in pomegranate seeds as dormancy was being broken by warm + cold stratification and by cold stratification alone. Embryos isolated from seeds after 1-42 days of warm stratification, after 56 days of warm stratification + 7, 28 or 56 days of cold stratification, and after 1-84 days of cold stratification alone, were used in biochemical tests. Hydrogen peroxide (H2O2), nitric oxide (NO), proline, lipid peroxidation, protein carbonylation, and activities of the scavenging enzymes superoxide dismutase (SOD), hydrogen peroxide enzyme and peroxidase in the embryos were assessed by colorimetric methods. Our results indicated that warm + cold stratification had a stronger dormancy-breaking effect than cold stratification (85% versus 50% germination), which may be attributed to a higher yield of H2O2, NO, lipid peroxidation and protein carbonylation in warm + cold stratification. Furthermore, warm + cold stratification-induced H2O2 change led to greater changes (elevation followed by attenuation) in activities of the scavenging enzymes than that induced by cold stratification alone. These results indicated that restriction of the level of reactive oxygen species change within a positive and safe range by such enzymes promoted seed germination. In addition, a relatively strong elevation of proline during warm + cold stratification also contributed to dormancy breakage and subsequent germination. In conclusion, the strong dormancy alleviating effect of warm + cold stratification on pomegranate seeds may be attributed to the corresponding active oxidative change via H2O2, NO, proline, malondialdehyde, protein carbonylation and

  20. The effect of transparency on stratification and mixing regime in lakes

    NASA Astrophysics Data System (ADS)

    Shatwell, Tom; Adrian, Rita; Kirillin, Georgiy

    2016-04-01

    The mixing regime is fundamentally important to lake ecology. Whereas shallow lakes mix to the bottom regularly, deep lakes tend to stratify seasonally. Water transparency strongly affects stratification duration and the mixing regime of lakes of intermediate depth. We review our recent research on how water transparency affects stratification duration and mixing regime in lakes. Firstly we derive physical scaling for the critical depth at which lakes switch from polymixis to seasonal stratification based on the radiation balance, the wind speed, water transparency and lake length. This scaling relation showed that the critical depth varies almost linearly with Secchi depth (transparency) and successfully classified the mixing regime of over 80% of the 379 lakes in our dataset. Secondly we investigated how seasonal variation in transparency due to phytoplankton affects stratification and mixing by analysing long term lake data and performing simulations with a hydrodynamic model. Here we found that the spring clear water phase, which is caused when zooplankton graze the spring phytoplankton bloom, can strongly influence stratification duration and sometimes also the mixing regime. Finally using model simulations of climate scenarios, we show how global warming and a change in transparency can potentially affect lake mixing regimes. Polymictic - dimictic regime shifts were more sensitive to transparency than warming, whereas dimictic - monomictic regime shifts were more sensitive to warming than transparency. Transparency has the strongest effect on stratification in clear lakes between 4 and 10 m deep. Changes in transparency due to biotic interactions or anthropogenic impact may lead to mixing regime shifts in these lakes.

  1. Molecular Reclassification of Crohn’s Disease: A Cautionary Note on Population Stratification

    PubMed Central

    Maus, Bärbel; Jung, Camille; Mahachie John, Jestinah M.; Hugot, Jean-Pierre; Génin, Emmanuelle; Van Steen, Kristel

    2013-01-01

    Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn’s disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn’s disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. PMID:24147066

  2. Evaluation of steam generator feedwater nozzles for the effects of thermal stratification

    SciTech Connect

    Qashu, R.; El-Akily, N.M.; Kuo, A.

    1995-12-01

    The potential for thermal stratification in the main feedwater (FW) line of a Pressurized Water Reactor (PWR) plant exists whenever the auxiliary feedwater is initiated. The thermal stratification phenomenon is attributed to the difference in density between the hotter normal feedwater, initially in the pipe, and the colder auxiliary feedwater introduced into the piping. The effect of thermal stratification on the fatigue life is two fold: the global bending due to the bowing effect caused by thermal stratification, and the local effect due to the fluctuation in the level of the hot-cold interface. This paper deals with the global and local effects of thermal stratification in the main feedwater line on the fatigue life of the steam generator feedwater nozzle. This nozzle, which is attached to the main feedwater line, is subjected to the effects of thermal stratification in the main feedwater line and in the nozzle itself due to the difference in the water density between the auxiliary feedwater and the steam generator. It should be noted that steam generator feedwater nozzle cracking has been a concern in the nuclear power industry since the late 1970`s.

  3. Income, social stratification, class, and private health insurance: a study of the Baltimore metropolitan area.

    PubMed

    Muntaner, C; Parsons, P E

    1996-01-01

    Most studies of inequalities and access to health care have used income as the sole indicator of social stratification. Despite the significance of social theory in health insurance research, there are no empirical studies comparing the ability of different models of social stratification to predict health insurance coverage. The aim of this study is to provide a comparative analysis using a variety of theory-driven indicators of social stratification and assess the relative strength of the association between these indicators and private health insurance. Data were collected in a 1993 telephone interview of a random digit dialing sample of the white population in the Baltimore Metropolitan Statistical Area. Indicators of social stratification included employment status, full-time work, education, occupation, industry, household income, firm size, and three types of assets: ownership, organizational, and skill/credential. The association between social stratification and private health insurance was strongest for those having higher household incomes, having attained at least a bachelor's degree, and working in a firm with more than 50 employees, followed by being an owner or manager, and by being employed. The addition of education and firm size improved the prediction of the household income model. The authors conclude that studies of inequalities in health insurance coverage can benefit from the inclusion of theory-driven indicators of social stratification such as human capital, labor market segmentation, and control over productive assets. PMID:8906444

  4. High resolution monitoring of episodic stratification events in an enclosed marine system

    NASA Astrophysics Data System (ADS)

    Sullivan, Timothy; Broszeit, Stefanie; O'Sullivan, Keith P. A.; McAllen, Rob; Davenport, John; Regan, Fiona

    2013-05-01

    While hypoxic and anoxic environments have existed throughout geological time, their frequency of occurrence in shallow coastal and estuarine areas appears to be increasing. However, few data are available on the physicochemical conditions at the boundary between anoxic and normoxic layers, including the conditions required for both formation and dissipation of stratification. Advances in autonomous environmental sensing technology have produced robust sensors capable of detailed measurements under inhospitable conditions created in such environments. In this study, an autonomous sensor approach was used to compare water column properties above and below the stratification before during and after dissipation of the stratification. Further, an investigation into the effect of the stratification on sedimentation rates of organic and inorganic matter and current speeds is reported here. Lough Hyne, a seasonally stratified temperate marine lake provided favourable conditions for this study. It was shown that temperatures dropped rapidly above the oxy-thermocline while increasing rapidly below the stratification, leading to a mixing of the complete water column. This was reflected in oxygen measurements below the stratification, which rose from anoxia to normoxic conditions over the same time period. During summer, the thermocline formed a barrier to organic matter sedimentation, reducing it significantly when present, while inorganic matter sedimentation was unaffected by the presence of thermocline. It also caused a reduction in current speeds below the thermocline.

  5. Occupational stratification, job-mismatches, and child poverty: understanding the disadvantage of Black immigrants in the US.

    PubMed

    Thomas, Kevin J A

    2015-03-01

    This study examines the implications of occupational stratification and job mismatches for the welfare of children, using data from the 2005-2009 American Community Survey. The results show that Black children of immigrants have household heads that are more likely to have occupations with low SEI scores than children in US-born households. More importantly, they demonstrate that intersections between parental job-mismatches and employment in the bottom rather than upper levels of the occupational distribution have important implications for understanding poverty differences among children. Job mismatches within occupations with low SEI scores are associated with greater poverty risks among Black than White, Asian, or Hispanic children of immigrants. However, racial poverty disparities are considerably lower among children with household heads in the highest occupational strata. PMID:25592931

  6. Predict amine solution properties accurately

    SciTech Connect

    Cheng, S.; Meisen, A.; Chakma, A.

    1996-02-01

    Improved process design begins with using accurate physical property data. Especially in the preliminary design stage, physical property data such as density viscosity, thermal conductivity and specific heat can affect the overall performance of absorbers, heat exchangers, reboilers and pump. These properties can also influence temperature profiles in heat transfer equipment and thus control or affect the rate of amine breakdown. Aqueous-amine solution physical property data are available in graphical form. However, it is not convenient to use with computer-based calculations. Developed equations allow improved correlations of derived physical property estimates with published data. Expressions are given which can be used to estimate physical properties of methyldiethanolamine (MDEA), monoethanolamine (MEA) and diglycolamine (DGA) solutions.

  7. Accurate thickness measurement of graphene

    NASA Astrophysics Data System (ADS)

    Shearer, Cameron J.; Slattery, Ashley D.; Stapleton, Andrew J.; Shapter, Joseph G.; Gibson, Christopher T.

    2016-03-01

    Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three-dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials.

  8. Dissolved oxygen stratification in two micro-tidal partially-mixed estuaries

    NASA Astrophysics Data System (ADS)

    Lin, Jing; Xie, Lian; Pietrafesa, Len J.; Shen, Jian; Mallin, Michael A.; Durako, Michael J.

    2006-11-01

    The controlling physical factors for vertical oxygen stratification in micro-tidal, partially-mixed estuaries are discussed in this paper. A theoretical deduction shows that vertical stratification of dissolved oxygen (DO) concentration can be explained by the extended Hansen and Rattray's Central Region theory, which suggests that in addition to biological factors such as photosynthesis, biochemical oxygen demand (BOD), sediment oxygen demand (SOD), vertical DO profiles are mainly controlled by physical factors such as surface re-aeration, river flow, and estuarine gravitational circulation. Vertical mixing of DO from surface re-aeration and photosynthesis sets a DO profile of higher concentration near the surface and lower near the bottom. With a positive seaward longitudinal DO gradient, strong river flow and estuarine gravitational circulation can cause lower DO concentrations near the surface and higher near the bottom. The actual vertical oxygen profile is then determined by the relative magnitude of the above-mentioned mechanisms. It is sensitive to two parameters: (1) the strength of the gravitational circulation ( uE); and (2) the relative importance between biochemical oxygen demand and vertical diffusivity ( α). Vertical DO stratification usually becomes weaker as uE increases. The impact of gravitational circulation on vertical oxygen distribution becomes more important for a larger α. The impact of α on oxygen stratification is profound. As uE (and river flow) increases, DO stratification appears to be less sensitive to the value of α. Surface-to-bottom differences in DO concentrations (ΔDO) is negligible when α is small ( α < 0.5). As α increases, ΔDO increases under a weak to moderate gravitational circulation mode ( uE ≤ 5 cm s -1). Under a strong gravitational circulation mode, ΔDO becomes negative with a small α ( α < 2), and as α continues to increase, ΔDO becomes positive. The newly-deduced governing equation for vertical oxygen

  9. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study

    PubMed Central

    Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-01-01

    Objective To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Design Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients’ designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Setting Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Participants Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. Main outcome measure ‘Suspected infection’ was the established gold standard to assess clinical decision support clinimetric performance. Results A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying ‘suspected infection’ as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. Conclusion A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis. PMID:26688744

  10. High resolution modelling of dense water formation in the Northwestern Mediterranean: benefits from an improved initial stratification in summer

    NASA Astrophysics Data System (ADS)

    Estournel, Claude; Testor, Pierre; Damien, Pierre; Mortier, Laurent; Marsaleix, Patrick; Lellouche, Jean-Michel; Ulses, Caroline; Kessouri, Faycal; Raimbault, Patrick; Coppola, Laurent

    2014-05-01

    The period that extends from summer 2012 to summer 2013 was the subject of several field campaigns in the northwestern Mediterranean that allowed to characterize the stratification on a seasonal scale in this region of deep water formation. This period is therefore ideal for testing hydrodynamic models and assessing the accuracy required on initial conditions and meteorological forcing. A 1 km resolution simulation of the vertical stratification evolution of the northwestern Mediterranean between summer 2012 and spring 2013 was conducted. The representation of winter convection was shown to be highly dependent on initial conditions in summer. A method was developed to correct the initial state of the model using the observations of the annual summer cruise of the MOOSE monitoring program and data from ARGO profilers. In addition, an adjustment of the wind helped to better approach winter observations, the criterion being the profile of residual buoyancy, simple index of the potential of the water column to convect more or less deeply and rapidly. The simulation obtained after correction of the initial conditions and wind forcing allowed to accurately represent the characteristics of the water masses formed during the convective period, the area concerned by convection and its timing. We will first present the methodology used to correct the initial state of the simulation, and then the validation of the simulation based on the observations from the DEWEX cruise (MERMEX program) and from profilers deployed in the frame of the HyMeX program. Then the volume of dense water formed and its characteristics will be quantified as well as their sensitivity to initial conditions.

  11. Testing for High-Risk APOL1 Alleles in Potential Living Kidney Donors.

    PubMed

    Riella, Leonardo V; Sheridan, Alice M

    2015-09-01

    Accurate risk assessment is critical when evaluating potential living kidney donors. High-risk kidney APOL1 variants have been associated with end-stage renal disease of multiple causes among African Americans, though the predictive power of these variants in population-based studies is small. No studies have looked at the effect of high-risk APOL1 alleles on donor outcomes, though few transplantation centers in the United States offer screening for APOL1 among African American donors. Screening all African Americans for high-risk APOL1 alleles may result in the exclusion of many potential donors (∼13% of African Americans). Such an exclusion may have a large effect on the availability of transplants for African Americans, who are already less likely to undergo transplantation. Nephrologists should be prepared to discuss with potential African American donors the relative increase in risk that is likely conferred by carrying 2 high-risk APOL1 alleles and how additional factors such as environmental exposures (eg, viral infections) and/or other genetic susceptibilities may be required for developing kidney disease. In this Perspective, we review the use of APOL1 testing for risk stratification of potential African American kidney donors. PMID:26049628

  12. Unusual nitrate distribution in an anticyclonic eddy during summer stratification.

    NASA Astrophysics Data System (ADS)

    Fernandez I., C.; Raimbault, P.; Caniaux, G.; Garcia, N.; Rimmelin, P.

    2003-04-01

    Typical open ocean eddies are usually recognized by vertical deformations in a density surface at the base of the euphotic zone. Cyclonic eddies can lift nutrients into the surface layer, which may be rapidly consumed by biota. On the contrary, anticyclonic eddies carry a deepening on density surface that eventually brings down nutrient depleted water, out of the euphotic zone. Aside these classical definitions, rare anticyclonic features known as “mode water eddies” have been reported to enhance a depression in the main thermocline while lifting the seasonal one, isolating intermediate water in the middle and leading to anomalous nutrient distribution in surface waters. In 2001, the POMME program (Programme Ocean Multidisciplinaire Meso Echelle) conducted three cruises from February to October in the Eastern North Atlantic (16° - 22°W, 38° - 45°N) in the vicinity of a mode water subduction area. Displacement of the σ ≈ 26.9 isopycne was intense near 41° - 42°N, characterizing the permanent mixed layer depth discontinuity zone (MLDZ). North of the MLDZ, winter convection controlled nutrient concentrations. Average mixing values oscillating between 100 and 75 m from winter to spring and allowed surface nitrate concentrations of over 5 to 7 µM until 44.5°N. In the southern area, no relationship was detected between convective mixing and integrated nitrates over the mixed layer. The main mesoscales features observed during the winter and spring cruises had no influence on nutrient distribution. Only one anticyclonic eddy (named A1) located permanently near 43°N, reflected some specific patterns. Changes in the inner structure of the eddy were observed in spring, when it evolved from a warm core to a cold core structure and finally behaved as a “mode water eddy” during summer stratification. A thick lens of water (σ ≈ 26.9-27) lifted the seasonal thermocline and depressed the main one. Consequently, surface nitrate concentrations greatly

  13. Accurate ab Initio Spin Densities

    PubMed Central

    2012-01-01

    We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as a basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys.2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insight into chemically interesting features of the molecule under study such as the distribution of α and β electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput.2011, 7, 2740]. PMID:22707921

  14. DrugTargetInspector: An assistance tool for patient treatment stratification.

    PubMed

    Schneider, Lara; Stöckel, Daniel; Kehl, Tim; Gerasch, Andreas; Ludwig, Nicole; Leidinger, Petra; Huwer, Hanno; Tenzer, Stefan; Kohlbacher, Oliver; Hildebrandt, Andreas; Kaufmann, Michael; Gessler, Manfred; Keller, Andreas; Meese, Eckart; Graf, Norbert; Lenhof, Hans-Peter

    2016-04-01

    Cancer is a large class of diseases that are characterized by a common set of features, known as the Hallmarks of cancer. One of these hallmarks is the acquisition of genome instability and mutations. This, combined with high proliferation rates and failure of repair mechanisms, leads to clonal evolution as well as a high genotypic and phenotypic diversity within the tumor. As a consequence, treatment and therapy of malignant tumors is still a grand challenge. Moreover, under selective pressure, e.g., caused by chemotherapy, resistant subpopulations can emerge that then may lead to relapse. In order to minimize the risk of developing multidrug-resistant tumor cell populations, optimal (combination) therapies have to be determined on the basis of an in-depth characterization of the tumor's genetic and phenotypic makeup, a process that is an important aspect of stratified medicine and precision medicine. We present DrugTargetInspector (DTI), an interactive assistance tool for treatment stratification. DTI analyzes genomic, transcriptomic, and proteomic datasets and provides information on deregulated drug targets, enriched biological pathways, and deregulated subnetworks, as well as mutations and their potential effects on putative drug targets and genes of interest. To demonstrate DTI's broad scope of applicability, we present case studies on several cancer types and different types of input -omics data. DTI's integrative approach allows users to characterize the tumor under investigation based on various -omics datasets and to elucidate putative treatment options based on clinical decision guidelines, but also proposing additional points of intervention that might be neglected otherwise. DTI can be freely accessed at http://dti.bioinf.uni-sb.de. PMID:26501925

  15. Stratification Studies with Sub Grade Iron Ore from Deposit No. 10 and 11A, Bacheli Complex, Bailadila, Chhattisgarh, India

    NASA Astrophysics Data System (ADS)

    Venkateswara Rao, Gottumukkala; Markandeya, Ravvala; Sharma, Satish Kumar

    2016-06-01

    Experiments were carried out with two different sizes of (-30 + 6 and -6 + 1 mm) sub grade iron ore sample from Deposit No. 10 and 11A, Bacheli Complex, Bailadila, India to study the stratification behaviour at optimised parameters in a under bed air pulsed jig at 1, 2, 5, 10, 15 and 20 minutes residence time. This paper deals with the rate at which stratification takes place and determines the optimum stratification time (residence time) for above two size fractions. Average apparent density along with Jig Stratification Index (JSI) of both the size fractions was calculated. It was observed that the stratification rate is high for fines (-6 + 1 mm) and stratification index was higher for lump (-30 + 6 mm) when compared with the other size fraction. The maximum JSI observed was 0.35 for lump (-30 + 6 mm) and 0.30 for fines (-6 + 1 mm).

  16. Antarctic density stratification and the strength of the circumpolar current during the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Lynch-Stieglitz, Jean; Ito, Takamitsu; Michel, Elisabeth

    2016-05-01

    The interaction between ocean circulation and biological processes in the Southern Ocean is thought to be a major control on atmospheric carbon dioxide content over glacial cycles. A better understanding of stratification and circulation in the Southern Ocean during the Last Glacial Maximum (LGM) provides information that will help us to assess these scenarios. First, we evaluate the link between Southern Ocean stratification and circulation states in a suite of climate model simulations. While simulated Antarctic Circumpolar Current (ACC) transport varies widely (80-350 Sverdrup (Sv)), it co-varies with horizontal and vertical stratification and the formation of the southern deep water. We then test the LGM simulations against available data from paleoceanographic proxies, which can be used to assess the density stratification and ACC transport south of Australia. The paleoceanographic data suggest a moderate increase in the Southern Ocean stratification and the ACC strength during the LGM. Even with the relatively large uncertainty in the proxy-based estimates, extreme scenarios exhibited by some climate models with ACC transports of greater than 250 Sv and highly saline Antarctic Bottom Water are highly unlikely.

  17. Stratification of the oceans: a global survey since the ARGO era

    NASA Astrophysics Data System (ADS)

    MAES, Christophe

    2015-04-01

    Of the many physical ocean processes contributing to the present climate changes, little attention has been paid to the large-scale contributions of stratification changes in the water column. Over the top part of the oceans, the rich variability in the vertical shapes and forms that the stratification structure can assume through variation in the atmospheric forcing results in a differential effect in terms of the temperature and salinity fields. Rather than focusing on the classical halocline vs thermocline definitions, the present study takes into account the respective thermal and saline dependencies in the Brunt-Vaisala frequency (N2) in order to isolate the specific role of the salinity stratification in the layers including the main permanent pycnocline. We evaluated observed estimates of long-term patterns and compare these to the corresponding thermal changes. Along the water column, the role of salinity is differentiated through its stabilizing or destabilizing effect on stratification. Beyond its role at the base of the mixed layer, the stabilizing effect of salinity as depicted by the ocean salinity stratification has been shown to be seasonally important above the main pycnocline in the tropical oceans. At the opposite, the destabilizing effect seems to be important in the subtropics where compensations with temperature have been previously observed. How these patterns are consistent with estimates of long-term water cycle amplification will be discussed.

  18. Influence of the Southern Ocean on the Global deep ocean stratification

    NASA Astrophysics Data System (ADS)

    Sun, S.; Eisenman, I.; Stewart, A.

    2015-12-01

    The stratification of the deep ocean plays a key role in the climate system by influencing the ocean circulation and regulating the outgassing of CO2. Previous studies have suggested that Southern Ocean processes control the global ocean stratification below the main thermocline (i.e., below ~500m). In this study, three ocean-only simulations are carried out with the Community Earth System Model (CESM1): one control simulation forced with Pre-industrial (PI) surface conditions, a second control simulation forced with Last Glacial Maximum (LGM) surface conditions, and a test simulation forced with LGM surface conditions in southern high latitudes and PI surface conditions elsewhere. We find that the test simulation does broadly reproduce the LGM density stratification of the global ocean below 2000m, but not at intermediate depths between 500m and 1500m. We propose a mechanism whereby the stratification of the intermediate-depth waters is influenced by the differing effects on the surface buoyancy distribution of fixed versus restoring aspects of the surface buoyancy forcing. This implies the Southern Ocean exerts less influence over the global deep ocean stratification than has been previously suggested, at least when considering the difference between LGM and PI climates in CESM1.

  19. Detection of anthropogenic influence on multi-decadal changes in ocean stratification

    NASA Astrophysics Data System (ADS)

    Andrews, Oliver; Le Quéré, Corinne

    2016-04-01

    Signals of anthropogenic climate change have been identified in the ocean system using established detection and attribution methods to examine historical records of ocean temperature, salinity and dissolved oxygen concentration. Strengthened stratification of the upper ocean is another likely consequence of climate-driven warming and freshening of near surface waters. However, whilst qualitative links have been made between climate forcing and observed and projected future ocean stratification, the relative contribution of natural and anthropogenic processes remains uncertain. Elevated density stratification reduces physical exchange between the surface and interior ocean, impacting upon ventilation processes and biogeochemical cycling. Here, we combine recent temperature and salinity measurements to assess the extent to which large-scale changes in ocean stratification between the 1960s and 2000s can be attributed to anthropogenic climate change using a suite of coupled climate model simulations. Applying formal, regression-based fingerprinting methods we show that external climate forcing has had a detectable influence on observed changes in density stratification and that these changes cannot be explained by climate variability or natural external factors such as volcanism or solar output. Our study indicates that human influence has already significantly altered the density structure of the upper ocean. We discuss the implications and potential for detecting the variability and trends in carbon and oxygen storage in the ocean and in heat uptake efficiency.

  20. Influence of thermal stratification on the surfacing and clustering of floaters in free surface turbulence

    NASA Astrophysics Data System (ADS)

    Lovecchio, Salvatore; Zonta, Francesco; Soldati, Alfredo

    2014-10-01

    The dispersion of floaters, small organic particles lighter than water, on the free surface of an open turbulent channel flow subject to thermal stratification is studied by Direct Numerical Simulation (DNS) of turbulence and Lagrangian Particle Tracking (LPT). Constant heat flux is maintained at the free surface of the channel, the bottom wall is adiabatic and the turbulent flow is driven by a pressure gradient. This archetypal flow setup mimics an environmentally plausible situation which can be found in terrestrial water bodies. The free surface turbulence characteristic of such flows has a strong influence on the distribution of the floaters: the objective of this work is to study the effect of different regimes of stable stratification on the surface distribution of floaters. The distribution of the floaters can possibly influence the transfer of chemical species across the water/atmosphere interface. Our results show that the modification of turbulence due to the thermal stratification strongly influences the settling velocity of floaters in the bulk of the flow. At the surface, stratification effects are also observed on the clustering of the floaters: the filamentary patterns of floaters observed in unstratified turbulence are progressively lost as thermal stratification increases, and the distribution of the floaters remains roughly two-dimensional.

  1. Consequences of an unstable chemical stratification on mantle dynamics

    NASA Astrophysics Data System (ADS)

    Plesa, Ana-Catalina; Tosi, Nicola; Breuer, Doris

    2013-04-01

    Early in the history of terrestrial planets, the fractional crystallization of primordial magma oceans may have led to the formation of large scale chemical heterogeneities. These may have been preserved over the entire planetary evolution as suggested for Mars by the isotopic analysis of the so-called SNC meteorites. The fractional crystallization of a magma ocean leads to a chemical stratification characterized by a progressive enrichment in heavy elements from the core-mantle boundary to the surface. This results in an unstable configuration that causes the overturn of the mantle and the subsequent formation of a stable chemical layering. Assuming scaling parameters appropriate for Mars, we first performed simulations of 2D thermo-chemical convection in Cartesian geometry with the numerical code YACC [1]. We investigated systems heated either solely from below or from within by varying systematically the buoyancy ratio B, which measures the relative importance of chemical to thermal buoyancy, and the mantle rheology, by considering systems with constant, strongly temperature-dependent and plastic viscosity. We ran a large set of simulations spanning a wide parameter space in order to understand the basic physics governing the magma ocean cumulate overturn and its consequence on mantle dynamics. Moreover, we derived scaling laws that relate the time over which chemical heterogeneities can be preserved (mixing time) and the critical yield stress (maximal yield stress that allows the lithosphere to undergo brittle failure) to the buoyancy ratio. We have found that the mixing time increases exponentially with B, while the critical yield stress shows a linear dependence. We investigated then Mars' early thermo-chemical evolution using the code GAIA in a 2D cylindrical geometry [2] and assuming a detailed magma ocean crystallization sequence as obtained from geochemical modeling [3]. We used an initial composition profile adapted from [3], accounted for an exothermic

  2. Stratification and energy fluxes in the anelastic convection model

    NASA Astrophysics Data System (ADS)

    Hejda, Pavel; Reshetnyak, Maxim

    2013-04-01

    Convection in the planetary cores is usually connected with the geostrophic state. At the onset of convection, the ratio of horizontal scale to the scale along the axis of rotation is proportional to the cube root of the Ekman number, which characterises the ratio of the viscous forces to the Coriolis force. The Ekman number is extremely small in the liquid cores, which is a source of strong anisotropy. Even if further increase of the heat sources leads to decrease of anisotropy, the final state is still highly anisotropic. The influence of the rapid rotation on the structure of the flows in the physical space is also manifested by a substantial change of the spectral properties of the turbulence in the core (Reshetnyak and Hejda, 2008; Hejda and Reshetnyak, 2009). If for the non-rotating flow the kinetic energy in the wave space propagates from the large scales to the small dissipative scales (the so-called direct Richardson-Kolmogorov cascade), then in presence of rotation the turbulence degenerates to the quasi two-dimensional state and the inverse cascade of the kinetic energy is observed. Having in mind that Cartesian and spherical geometries exhibit similar results and reproduce the inverse cascades of the kinetic energy (Reshetnyak and Hejda, 2012), there is an open question how this cascade contributes to the more general energy balance, which includes the heat flux equation. As the heat energy definition in the Boussinesq model is quite questionable, we consider the anelastic model, where the heat fluxes can be compared with the kinetic energy fluxes in the adequate way. Here we consider the spherical geometry model in the shell that limits our study to the cascades in the azimuthal wave-number. As the self-consistent anelastic model includes new term, the adiabatic cooling, which produces "stratification" in the outer part of the core, we consider its influence on convection in the physical and wave spaces. We show that even small cooling can change the

  3. When is risk stratification by race or ethnicity justified in medical care?

    PubMed

    Chin, Marshall H; Humikowski, Catherine A

    2002-03-01

    Issues of race and ethnicity have been controversial in both clinical care and medical education. In daily practice, many physicians struggle to be culturally competent and avoid racial stereotyping. One educational development that makes this goal more complex is the rise of clinical epidemiology and Bayesian thinking. These population-based, probabilistic approaches to medicine help guide the diagnostic and therapeutic pathways for patients, and are foundations of the evidence-based medicine movement. Can Bayesian thinking be applied effectively to issues of race and ethnicity in medical care, or are the dangers of prejudicial stereotyping too great? The authors draw upon lessons from recent cases of racial profiling, and develop a conceptual framework for thinking about ethnicity as a clinical tool. In their typology of ethnicity as a proxy, they argue that the costs of using ethnicity as a proxy for socioeconomic status and behavior are too high, but that ethnicity may appropriately be used as an initial proxy for history, language, culture, and health beliefs. They discuss their approach within the context of new curricula in cultural competence, and argue that viewing the patient within a wider cultural setting can help guide the initial clinical approach, but individualized care is mandatory. Also, physicians must remain sensitive to the changing nature of cultural norms; thus lifelong learning and flexibility are necessary. PMID:11891155

  4. Risk Stratification for Ulnar Collateral Ligament Injury in Major League Baseball Players

    PubMed Central

    DeFroda, Steven F.; Kriz, Peter K.; Hall, Amber M.; Zurakowski, David; Fadale, Paul D.

    2016-01-01

    Background: Ulnar collateral ligament (UCL) injury has become increasingly common in Major League Baseball (MLB) players in recent years. Hypothesis: There is a significant difference in preinjury fastball velocity between MLB pitchers with tears and matched controls without UCL injury. Pitchers with injuries are throwing harder and getting injured earlier in their MLB careers. Study Design: Cohort study; Level of evidence, 3. Methods: From 2007 to 2014, a total of 170 documented UCL injuries (156 pitchers, 14 position players) occurred in MLB. Inclusion criteria for this study consisted of any player who tore his UCL in MLB during this time frame. There were 130 regular-season tears (April-September). From this group, 118 players who pitched more than 100 innings prior to tear were matched to subjects with no tear and were compared using a logistic regression analysis. A subgroup of “early tear” players who threw less than 100 career innings (n = 37) was also identified and compared with the larger tear group using a logistic regression analysis. Results: Of the 130 tears that occurred during the regular season, a significantly larger number (62%) occurred in the first 3 months (P = .011). The rate of UCL tears per MLB player (P = .001) was statistically significant. In the group of 118 matched tears, the mean fastball velocity was greater in the tear group (91.7 mph) compared with the control group (91.0 mph; P = .014). Furthermore, relief pitchers made up a greater percentage of the early tear group (<100 innings) compared with the later tear group (P = .011). Sixteen of the 170 UCL tears (9.4%) were recurrent tears, with 5 of 16 experiencing both tear and retear within the past 4 years. Conclusion: There is a statistically significant difference in the mean fastball velocity of pitchers who injure their UCL. Small increases in pitcher fastball velocity are a main contribution to the increased rate of tear in MLB. In addition, there has been an increased incidence of injury in the first 3 months of the season. Finally, early tears are more likely to occur in relief pitchers than starters. PMID:26848482

  5. Risk stratification for cardiac death in hemodialysis patients without obstructive coronary artery disease.

    PubMed

    Nishimura, Masato; Tsukamoto, Kazumasa; Tamaki, Nagara; Kikuchi, Kenjiro; Iwamoto, Noriyuki; Ono, Toshihiko

    2011-02-01

    The incidence of cardiac death is higher among patients receiving dialysis compared with the general population. Although obstructive coronary artery disease is involved in cardiac deaths in the general population, deaths in hemodialysis patients occur in the apparent absence of obstructive coronary artery disease. To study this further, we prospectively enrolled 155 patients receiving hemodialysis after angiography had confirmed the absence of obstructive coronary lesions. All patients were examined by single-photon emission computed tomography using the iodinated fatty acid analog, BMIPP, the uptake of which was graded in 17 standard myocardial segments and assessed as summed scores. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). During a mean follow-up of 5.1 years, 42 patients died of cardiac events. Stepwise Cox hazard analysis associated cardiac death with reduced BMIPP uptake and increased insulin resistance. Patients were assigned to subgroups based on BMIPP summed scores and HOMA-IR cutoff values for cardiac death of 12 and 5.1, respectively, determined by receiver operating characteristic analysis. Cardiac death-free survival rates at 5 years were the lowest (32.2%) in the subgroup with both a summed score and assessment equal to or above the cutoff values compared with any other combination (52.9-98.7%) above, equal to, or below the thresholds. Thus, impaired myocardial fatty acid metabolism and insulin resistance may be associated with cardiac death among hemodialysis patients without obstructive coronary artery disease. PMID:20944544

  6. Risk stratification with exercise N13-ammonia PET in adults with anomalous right coronary arteries

    PubMed Central

    Cremer, Paul C; Mentias, Amgad; Koneru, Srikanth; Schoenhagen, Paul; Majdalany, David; Lorber, Richard; Flamm, Scott D; Hobbs, Robert E; Pettersson, Gosta; Jaber, Wael A

    2016-01-01

    Objective In adults with an interarterial and intramural course of an anomalous right coronary artery from the left sinus (AAORCA), surgical unroofing is recommended in the setting of myocardial ischaemia. However, data regarding functional testing are limited, and the management of adults without ischaemia is unclear. To evaluate these patients, we employed an exercise N13-ammonia positron emission tomography (PET) protocol. We hypothesised that patients with typical angina and exertional dyspnoea would be more likely to have ischaemia and that patients without ischaemia could be managed conservatively. Methods Between July 2008 and December 2014, we retrospectively identified 27 consecutive patients >18 years old with an interarterial and intramural course of an AAORCA who had exercise N13-ammonia PET. Results The majority of patients had anatomic delineation with cardiac CT (25, 93%), and most patients had chest pain (24, 89%). Myocardial ischaemia with PET was common (13, 48%), and ischaemia was more likely in patients with typical angina and exertional dyspnoea (p<0.05). Surgery was performed in 12 patients including 11 patients with ischaemia. At a median follow-up of 245 days, there were no deaths in patients with surgery or in patients managed conservatively. Conclusions In patients with an interarterial and intramural course of an AAORCA, typical angina and exertional dyspnoea are associated with ischaemia on exercise N13-ammonia PET. Referral for surgical unroofing in symptomatic patients with ischaemia on exercise N13-ammonia PET and initial conservative management in patients without ischaemia seems appropriate, though larger studies with long-term follow-up are needed. PMID:27621834

  7. Usefulness of T-wave alternans in sudden death risk stratification and guiding medical therapy.

    PubMed

    Nieminen, Tuomo; Verrier, Richard L

    2010-07-01

    Visible T-wave alternans (TWA), a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed for over a century to occur in association with life-threatening arrhythmias in patients with acute coronary syndrome, heart failure, and cardiac channelopathies. This compelling linkage prompted development of quantitative techniques leading to FDA-cleared commercial methodologies for measuring nonvisible levels of TWA in the frequency and time domains. The first aim of this review is to summarize evidence from more than a hundred studies enrolling a total of >12,000 patients that support the predictivity of TWA for cardiovascular mortality and sudden cardiac death. The second focus is on the usefulness of TWA in guiding therapy. Until recently, TWA has been used primarily in decision making for cardioverter-defibrillator implantation. Its potential utility in guiding pharmacologic therapy has been underappreciated. We review clinical literature supporting the usefulness of TWA as an index of antiarrhythmic effects and proarrhythmia for different drug classes. Beta-adrenergic and sodium channel-blocking agents are the most widely studied drugs in clinical TWA investigations, with both reducing TWA magnitude; the exception is patients in whom sodium channel blockade discloses the Brugada syndrome and provokes macroscopic TWA. An intriguing possibility is that TWA may help to detect beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which indirectly protects from arrhythmia through improving myocardial remodeling. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic intervention and thereby serve as a therapeutic target. PMID:20645971

  8. Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib

    PubMed Central

    Ramaswamy, Anant; Jain, Deepak; Sahu, Arvind; Ghosh, Joydeep; Prasad, Priya; Deodhar, Kedar; Shetty, Nitin; Banavali, Shripad; Shrikhande, Shailesh

    2016-01-01

    Background Multimodality treatment of gastrointestinal stromal tumor (GIST) with surgery and adjuvant imatinib mesylate (IM), along with an emerging role for neoadjuvant IM prior to evaluation for resectability has resulted in high survival rates. Methods We conducted a retrospective analysis of prospectively collected data of patients who underwent surgery for GIST, prior to or followed by IM therapy. A total of 112 patients underwent surgery between January 2009 and March 2015 at our centre. This included 27 patients with upfront resectable disease, 76 patients with locally advanced GIST who received neoadjuvant IM followed by surgery and 9 patients with metastatic disease who had excellent response to IM and were taken for surgery. Results The primary tumor in the non metastatic patients was in the stomach (53%), duodenum (16%), rectum (12%), jejunum (11%), ileum (7%), and others (2%). Median duration of neoadjuvant IM was 5 months with 4 patients showing disease progression during neoadjuvant IM. Ninety-three percent of all patients had R0 resections, while 7% had R+ resections. The estimated 3- and 5-year DFS in non-metastatic patients was 86.1% and 67% respectively with a 3- and 5-year median OS of 95.4% and 91.7% respectively. Five-year PFS and OS for the metastatic patients was 88.8% and 100% respectively. Lack of adjuvant IM was the only factor related to inferior PFS and OS. Conclusions Longer duration of neoadjuvant IM should be considered in locally advanced GIST prior to surgery and resection may be considered in responding metastatic patients. PMID:27563454

  9. Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update

    PubMed Central

    Pui, Ching-Hon; Carroll, William L.; Meshinchi, Soheil; Arceci, Robert J.

    2011-01-01

    Purpose We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research. Methods A review of English literature on childhood acute leukemias from the past 5 years was performed. Results Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients. Conclusion The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade. PMID:21220611

  10. Cardiac MRI and Ischemic Heart Disease: Role in Diagnosis and Risk Stratification.

    PubMed

    Sawlani, Rahul N; Collins, Jeremy D

    2016-05-01

    Cardiac magnetic resonance imaging (CMRI) has been under development for the past four decades and has more recently become an essential tool in the evaluation of ischemic heart disease (IHD). It is the reference standard for quantification of both right and left ventricular volume and function and, after landmark work published in the New England Journal of Medicine in 2000, has proven effective in identifying hibernating myocardium, or hypokinetic myocardium that will recover after revascularization. More recent literature continues to support both delayed enhancement imaging and CMRI stress perfusion as essential tools in evaluating IHD. This review will briefly address the basics of CMRI and the scientific literature supporting the use of CMRI in IHD. It will then address more recent clinical studies establishing the clinical utility of CMRI in IHD, followed by a discussion of future directions in CMRI. PMID:26980317

  11. Acute myeloid leukemia: 2016 Update on risk-stratification and management.

    PubMed

    Estey, Elihu

    2016-08-01

    Evidence suggest that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment related mortality and resistance to therapy, the latter the principal cause of failure even in patients aged 70 or above. We emphasize the limitations of prediction of resistance based only on pre- treatment factors and stress the need to incorporate post-treatment factors, for example indicators of minimal residual disease. We review various newer therapeutic options and considerations that underlie the decision to recommend allogeneic hematopoietic cell transplant. Am. J. Hematol. 91:825-846, 2016. © 2016 Wiley Periodicals, Inc. PMID:27417880

  12. Nonsustained Ventricular Tachycardia in the Normal Heart: Risk Stratification and Management.

    PubMed

    Marine, Joseph E

    2016-09-01

    Nonsustained ventricular tachycardia (NSVT) may trigger concern, particularly in patients with known congestive heart failure, structural heart disease, or prolonged QT interval. When NSVT occurs in patients with normal hearts, it usually has a benign prognosis. Therefore, establishing the presence or absence of structural or inherited heart disease is a critical step in each patient's evaluation. It is important to approach a wide-complex tachycardia in a systematic manner, to ensure correct diagnosis and treatment. When NSVT occurs in a patient with a normal heart, treatment is targeted toward symptoms and may consist of observation, medical therapy, or catheter ablation. PMID:27521087

  13. Analysis and optimization of thermal stratification and self-pressurization effects in liquid hydrogen storage systems -- Part 1: Model development

    SciTech Connect

    Gursu, S.; Veziroglu, T.N. . Clean Energy Research Inst.); Sherif, S.A. . Dept. of Mechanical Engineering); Sheffield, J.W. )

    1993-09-01

    This paper reports on analyses and optimization studies of problems associated with liquid hydrogen thermal stratification and self-pressurization in cryogenic vessels. Three different pressure rise models were employed to calculate the self-pressurization and boil-off rates. These are a homogeneous model, a surface-evaporation model, and a thermal stratification model. The first two models are based on the assumption that no temperature gradients exist in the tank, while the thermal stratification model takes the temperature distribution into account. Employing the thermal stratification model, temperature gradients and their effect on the pressure rise rates in liquid hydrogen tanks are analyzed.

  14. Morphological origin for the stratification of P3HT:PCBM blend film studied by neutron reflectometry

    SciTech Connect

    Keum, Jong Kahk; Center for Nanophase Material Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 ; Browning, James F.; Halbert, Candice E.; Xiao, Kai; Shao, Ming; Hong, Kunlun

    2013-11-25

    Understanding the origin for the film stratification of electron donor/acceptor blend is crucial for high efficiency organic photovoltaic cell. In this study, P3HT:PCBM blend is deposited onto hydrophilic and hydrophobic substrate to examine the film stratifications. The neutron reflectivity results show that, on the different surfaces, PCBM diffuses toward the two interfacial regions in an identical fashion during thermal annealing. This evidences that the film stratification is not affected by the substrates. Instead, since P3HT remains more amorphous in the interfacial regions and PCBM is miscible with amorphous P3HT, PCBM preferentially diffuses to the interfacial regions, resulting in the stratification.

  15. Semi-supervised spectral clustering with application to detect population stratification

    PubMed Central

    Liu, Binghui; Shen, Xiaotong; Pan, Wei

    2013-01-01

    In genetic association studies, unaccounted population stratification can cause spurious associations in a discovery process of identifying disease-associated genetic markers. In such a situation, prior information is often available for some subjects' population identities. To leverage the additional information, we propose a semi-supervised clustering approach for detecting population stratification. This approach maintains the advantages of spectral clustering, while is integrated with the additional identity information, leading to sharper clustering performance. To demonstrate utility of our approach, we analyze a whole-genome sequencing dataset from the 1000 Genomes Project, consisting of the genotypes of 607 individuals sampled from three continental groups involving 10 subpopulations. This is compared against a semi-supervised spectral clustering method, in addition to a spectral clustering method, with the known subpopulation information by the Rand index and an adjusted Rand (ARand) index. The numerical results suggest that the proposed method outperforms its competitors in detecting population stratification. PMID:24298278

  16. Summer/winter stratification variability in the central part of the South Brazil Bight

    NASA Astrophysics Data System (ADS)

    Castro, Belmiro M.

    2014-10-01

    Analysis of the hydrographic data collected during seven consecutive high resolution summer/winter cruises in the central part of the South Brazil Bight off the coastal city of Ubatuba confirmed an observable summer/winter stratification variability of the shelf waters. The maximum bulk stratification occurred at mean distances of 85.6 km and 39.1 km from the coast in the austral winter and summer cruises, respectively. Estimates of the equivalent mixing power of the physical processes that increase or decrease the stratification in the inner and middle shelves showed that both shelf regions would be vertically well mixed were it not for buoyancy advection. In the inner shelf, buoyancy advection was associated with the along-shelf transport of low salinity waters originating from river runoff. In the middle shelf, buoyancy advection was due to the oceanic South Atlantic Central Water intrusions toward the coast.

  17. Effect of thermal stratification on free convection in a fluid-saturated porous enclosure

    SciTech Connect

    Kumar, B.V.R.; Singh, P.

    1998-08-28

    Natural convection heat transfer from an isothermal vertical surface in a fluid-saturated porous medium under the influence of thermal stratification has been numerically analyzed using the finite element method. The combined effect of Rayleigh number and thermal stratification on the global heat flux in porous cavities of varying aspect ratios has been analyzed. It is observed that the global heat flux (1) decreases with increasing values of the thermal stratification b and (2) increases with increasing values of Rayleigh number Ra. However, the cumulative heat flux along the midsegment of the vertical wall increases with increasing b and decreases with Ra. With increasing b, a reduction in the convection zone with a downward drift is noticed. Global heat flux can be boosted by reducing the width L of the cavity by a factor of {approximately}8 or more. The flow field and the heat transfer results are presented through the streamlines, isotherms, and global heat flux plots.

  18. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  19. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  20. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...