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Sample records for accurate risk stratification

  1. Towards actionable risk stratification: a bilinear approach.

    PubMed

    Wang, Xiang; Wang, Fei; Hu, Jianying; Sorrentino, Robert

    2015-02-01

    Risk stratification is instrumental to modern clinical decision support systems. Comprehensive risk stratification should be able to provide the clinicians with not only the accurate assessment of a patient's risk but also the clinical context to be acted upon. However, existing risk stratification techniques mainly focus on predicting the risk score for individual patients; at the cohort level, they offer little insight beyond a flat score-based segmentation. This essentially reduces a patient to a score and thus removes him/her from his/her clinical context. To address this limitation, in this paper we propose a bilinear model for risk stratification that simultaneously captures the three key aspects of risk stratification: (1) it predicts the risk of each individual patient; (2) it stratifies the patient cohort based on not only the risk score but also the clinical characteristics; and (3) it embeds all patients into clinical contexts with clear interpretation. We apply our model to a cohort of 4977 patients, 1127 among which were diagnosed with Congestive Heart Failure (CHF). We demonstrate that our model cannot only accurately predict the onset risk of CHF but also provide rich and actionable clinical insights into the patient cohort.

  2. Sudden cardiac death risk stratification.

    PubMed

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

    2015-06-05

    Arrhythmic sudden cardiac death (SCD) may be caused by ventricular tachycardia/fibrillation or pulseless electric activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our healthcare and research resources to tackle this important public health issue. Although our understanding of SCD because of pulseless electric activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-ventricular tachycardia/ventricular fibrillation. This review focuses on existing and novel risk stratification tools for SCD-ventricular tachycardia/ventricular fibrillation. For patients with left ventricular dysfunction 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-ventricular tachycardia/ventricular fibrillation 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.

  3. Cardiac risk stratification and protection.

    PubMed

    Halub, Meghan E; Sidwell, Richard A

    2015-04-01

    The goal of preoperative cardiac evaluation is to screen for undiagnosed cardiac disease or to find evidence of known conditions that are poorly controlled to allow management that reduces the risk of perioperative cardiac complications. A careful history and physical examination combined with the procedure-specific risk is the cornerstone of this assessment. This article reviews a brief history of prior cardiac risk stratification indexes, explores current practice guidelines by the American College of Cardiology and the American Heart Association Task Force, reviews current methods for preoperative evaluation, discusses revascularization options, and evaluates perioperative medication recommendations.

  4. Novel concepts for risk stratification in prostate cancer.

    PubMed

    Patel, Keval M; Gnanapragasam, Vincent J

    2016-12-01

    Since Partin introduced the analysis of prostate-specific antigen, clinical T-stage and Gleason scores to estimate the risk of progression in men with localised prostate cancer, our understanding of factors that modify this risk has changed drastically. There are now multiple risk stratification tools available, including look-up tables, risk stratification/classification analyses, regression-tree analyses, nomograms and artificial neural networks. Concurrently, descriptions of novel biopsy strategies, imaging modalities and biomarkers are frequently published with the aim of improving risk stratification. With an abundance of new information available, incorporating advances into clinical practice can be confusing. This article aims to outline the major novel concepts in prostate cancer risk stratification for men with biopsy confirmed prostate cancer. We will detail which of these novel techniques and tools are likely to be adopted to aid treatment decisions and enable more accurate post-diagnosis, pretreatment risk stratification.

  5. Novel concepts for risk stratification in prostate cancer

    PubMed Central

    Patel, Keval M; Gnanapragasam, Vincent J

    2016-01-01

    Since Partin introduced the analysis of prostate-specific antigen, clinical T-stage and Gleason scores to estimate the risk of progression in men with localised prostate cancer, our understanding of factors that modify this risk has changed drastically. There are now multiple risk stratification tools available, including look-up tables, risk stratification/classification analyses, regression-tree analyses, nomograms and artificial neural networks. Concurrently, descriptions of novel biopsy strategies, imaging modalities and biomarkers are frequently published with the aim of improving risk stratification. With an abundance of new information available, incorporating advances into clinical practice can be confusing. This article aims to outline the major novel concepts in prostate cancer risk stratification for men with biopsy confirmed prostate cancer. We will detail which of these novel techniques and tools are likely to be adopted to aid treatment decisions and enable more accurate post-diagnosis, pretreatment risk stratification.

  6. Brugada Syndrome:Risk Stratification And Management.

    PubMed

    Letsas Md Fesc, Konstantinos P; Georgopoulos Md, Stamatis; Vlachos Md, Konstantinos; Karamichalakis Md, Nikolaos; Liatakis Md, Ioannis; Korantzopoulos Md PhD, Panagiotis; Liu Md PhD, Tong; Efremidis Md, Michael; Sideris Md, Antonios

    2016-01-01

    The Brugada syndrome (BrS) is an arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. The risk stratification and management of BrS patients, particularly of asymptomatic ones, still remains challenging. A previous history of aborted sudden cardiac death or arrhythmic syncope in the presence of spontaneous type 1 ECG pattern of BrS phenotype appear to be the most reliable predictors of future arrhythmic events. Several other ECG parameters have been proposed for risk stratification. Among these ECG markers, QRS-fragmentation appears very promising. Although the value of electrophysiological study still remains controversial, it appears to add important information on risk stratification, particularly when incorporated in multiparametric scores in combination with other known risk factors. The present review article provides an update on the pathophysiology, risk stratification and management of patients with BrS.

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

    PubMed

    Omry-Orbach, Gal

    2016-01-28

    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

  8. Brugada syndrome: Diagnosis, risk stratification and management.

    PubMed

    Gourraud, Jean-Baptiste; Barc, Julien; Thollet, Aurélie; Le Marec, Hervé; Probst, Vincent

    2017-03-01

    Brugada syndrome is a rare inherited arrhythmia syndrome leading to an increased risk of sudden cardiac death, despite a structurally normal heart. Diagnosis is based on a specific electrocardiogram pattern, observed either spontaneously or during a sodium channel blocker test. Among affected patients, risk stratification remains a challenge, despite recent insights from large population cohorts. As implantable cardiac defibrillators - the main therapy in Brugada syndrome - are associated with a high rate of complications in this population, the main challenge is risk stratification of patients with Brugada syndrome. Aside from the two main predictors of arrhythmia (symptoms and spontaneous electrocardiogram pattern), many risk factors have been recently suggested for stratifying risk of sudden cardiac death in Brugada syndrome. We have reviewed these data and discuss current guidelines in light of recent progress in this complex field.

  9. 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.

  10. Life insurance: genomic stratification and risk classification.

    PubMed

    Joly, Yann; Burton, Hilary; Knoppers, Bartha Maria; Feze, Ida Ngueng; Dent, Tom; Pashayan, Nora; Chowdhury, Susmita; Foulkes, William; Hall, Alison; Hamet, Pavel; Kirwan, Nick; Macdonald, Angus; Simard, Jacques; Van Hoyweghen, Ine

    2014-05-01

    With the development and increasing accessibility of new genomic tools such as next-generation sequencing, genome-wide association studies, and genomic stratification models, the debate on genetic discrimination in the context of life insurance became even more complex, requiring a review of current practices and the exploration of new scenarios. In this perspective, a multidisciplinary group of international experts representing different interests revisited the genetics and life insurance debate during a 2-day symposium 'Life insurance: breast cancer research and genetic risk prediction seminar' held in Quebec City, Canada on 24 and 25 September 2012. Having reviewed the current legal, social, and ethical issues on the use of genomic information in the context of life insurance, the Expert Group identified four main questions: (1) Have recent developments in genomics and related sciences changed the contours of the genetics and life insurance debate? (2) Are genomic results obtained in a research context relevant for life insurance underwriting? (3) Should predictive risk assessment and risk stratification models based on genomic data also be used for life insurance underwriting? (4) What positive actions could stakeholders in the debate take to alleviate concerns over the use of genomic information by life insurance underwriters? This paper presents a summary of the discussions and the specific action items recommended by the Expert Group.

  11. Life insurance: genomic stratification and risk classification

    PubMed Central

    Joly, Yann; Burton, Hilary; Knoppers, Bartha Maria; Feze, Ida Ngueng; Dent, Tom; Pashayan, Nora; Chowdhury, Susmita; Foulkes, William; Hall, Alison; Hamet, Pavel; Kirwan, Nick; Macdonald, Angus; Simard, Jacques; Van Hoyweghen, Ine

    2014-01-01

    With the development and increasing accessibility of new genomic tools such as next-generation sequencing, genome-wide association studies, and genomic stratification models, the debate on genetic discrimination in the context of life insurance became even more complex, requiring a review of current practices and the exploration of new scenarios. In this perspective, a multidisciplinary group of international experts representing different interests revisited the genetics and life insurance debate during a 2-day symposium ‘Life insurance: breast cancer research and genetic risk prediction seminar' held in Quebec City, Canada on 24 and 25 September 2012. Having reviewed the current legal, social, and ethical issues on the use of genomic information in the context of life insurance, the Expert Group identified four main questions: (1) Have recent developments in genomics and related sciences changed the contours of the genetics and life insurance debate? (2) Are genomic results obtained in a research context relevant for life insurance underwriting? (3) Should predictive risk assessment and risk stratification models based on genomic data also be used for life insurance underwriting? (4) What positive actions could stakeholders in the debate take to alleviate concerns over the use of genomic information by life insurance underwriters? This paper presents a summary of the discussions and the specific action items recommended by the Expert Group. PMID:24129434

  12. 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.

  13. Risk stratification for benign prostatic hyperplasia.

    PubMed

    Zattoni, Fabio; Ficarra, Vincenzo; Novara, Giacomo

    2017-03-18

    Benign prostatic hyperplasia (BPH) represents an important public health problem in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a progressive disease, mainly characterized by a worsening of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention and need for BPH-related surgery. The management of BPH and LUTS in men should move forward its focus on symptom control only. Indeed, the goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes in order to optimize their management and reduce complications. Risk stratification and tailored treatment should improve the reductions in both symptoms and the long-term consequences of BPH and BPH treatments. To do this, clinicians need to know possible factors that may support the develop of PBH and possible risks due to the BPH itself.

  14. 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

  15. 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

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

    PubMed

    Corcoran, David; Grant, Patrick; Berry, Colin

    2015-09-01

    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.

  17. [Risk stratification of sudden death in hypertrophic cardiomyopathy in 2016].

    PubMed

    Dubourg, Olivier; Charron, Philippe; Sirol, Marc; Siam-Tsieu, Valérie; Mansencal, Nicolas

    2016-10-01

    Patients with hypertrophic cardiomyopathy (HCM) are at an increased risk of death from many causes and sudden cardiac death is one of them. The study of the sudden cardiac death of patients with HCM has allowed the identification of risk factors and among them major risk factor are: family history of sudden cardiac death, the occurrence of syncope/dizziness, the existence of non-sustained ventricular tachycardia an abnormal blood pressure response during stress test, presence of severe left ventricular hypertrophy≥30mm. Risk stratification for sudden cardiac death is essential, for symptomatic or asymptomatic HCM patients. Two approaches are possible: the classical approach or risk stratification methods with major risk factors and the new approach using the risk-calculator recommended by the ESC. Both methods are not in opposition but complementary. The risk stratification in hypertrophic cardiomyopathy should be still improved to be sure that only the most high-risk patients receive an implantable cardiac defibrillator.

  18. Risk stratification in heart failure using artificial neural networks.

    PubMed Central

    Atienza, F.; Martinez-Alzamora, N.; De Velasco, J. A.; Dreiseitl, S.; Ohno-Machado, L.

    2000-01-01

    Accurate risk stratification of heart failure patients is critical to improve management and outcomes. Heart failure is a complex multisystem disease in which several predictors are categorical. Neural network models have successfully been applied to several medical classification problems. Using a simple neural network, we assessed one-year prognosis in 132 patients, consecutively admitted with heart failure, by classifying them in 3 groups: death, readmission and one-year event-free survival. Given the small number of cases, the neural network model was trained using a resampling method. We identified relevant predictors using the Automatic Relevance Determination (ARD) method, and estimated their mean effect on the 3 different outcomes. Only 9 individuals were misclassified. Neural networks have the potential to be a useful tool for making prognosis in the domain of heart failure. PMID:11079839

  19. From Humoral Theory to Performant Risk Stratification in Kidney Transplantation.

    PubMed

    Lefaucheur, C; Viglietti, D; Mangiola, M; Loupy, A; Zeevi, A

    2017-01-01

    The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection. Consequently, the presence of circulating anti-HLA DSA does not provide a sufficient level of accuracy for the risk stratification of allograft outcomes. Enhancing the predictive performance of anti-HLA DSA is currently one of the most pressing unmet needs for facilitating individualized treatment choices that may improve outcomes. Recent advancements in the assessment of anti-HLA DSA properties, including their strength, complement-binding capacity, and IgG subclass composition, significantly improved the risk stratification model to predict allograft injury and failure. Although risk stratification based on anti-HLA DSA properties appears promising, further specific studies that address immunological risk stratification in large and unselected populations are required to define the benefits and cost-effectiveness of such comprehensive assessment prior to clinical implementation.

  20. From Humoral Theory to Performant Risk Stratification in Kidney Transplantation

    PubMed Central

    Viglietti, D.; Mangiola, M.; Loupy, A.; Zeevi, A.

    2017-01-01

    The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection. Consequently, the presence of circulating anti-HLA DSA does not provide a sufficient level of accuracy for the risk stratification of allograft outcomes. Enhancing the predictive performance of anti-HLA DSA is currently one of the most pressing unmet needs for facilitating individualized treatment choices that may improve outcomes. Recent advancements in the assessment of anti-HLA DSA properties, including their strength, complement-binding capacity, and IgG subclass composition, significantly improved the risk stratification model to predict allograft injury and failure. Although risk stratification based on anti-HLA DSA properties appears promising, further specific studies that address immunological risk stratification in large and unselected populations are required to define the benefits and cost-effectiveness of such comprehensive assessment prior to clinical implementation. PMID:28133619

  1. Testicular cancer: risk stratification in adolescents with nonseminoma.

    PubMed

    Looijenga, Leendert H J

    2014-07-01

    Data are lacking on the role of histological risk factors (such as embryonal carcinoma and lymphovascular invasion) for occult metastasis in adolescents with testicular germ cell tumours. Investigators of a pilot study have now retrospectively reviewed a testis cancer database to identify risk stratification criteria in this population.

  2. Risk stratification in ductal carcinoma in situ: the role of genomic testing.

    PubMed

    Freedman, Gary M

    2013-02-01

    From the earliest days of conservative surgery for ductal carcinoma in situ (DCIS) of the breast, there have been attempts to identify patients who may not need postoperative radiation. Randomized prospective trials have not identified a population for whom there is no benefit to radiation. However, decades of studies of clinical, radiological and pathologic correlates to local recurrence have led to criteria for a patient subgroup at low risk for local recurrence after omission of radiation. Gene expression profiling for invasive breast cancer has been used to identify patients at low, intermediate or high risk for distant recurrence. Application of this methodology to DCIS aims to identify patients at low, intermediate or high risk for local recurrence. Whether this method of risk stratification will prove more accurate than clinical, radiological and pathologic risk stratification, or identify patients with little to no clinical benefit from radiation, remains to be seen.

  3. 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

  4. Risk stratification in prostate cancer screening.

    PubMed

    Roobol, Monique J; Carlsson, Sigrid V

    2013-01-01

    Screening for prostate cancer is a controversial topic within the field of urology. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial did not demonstrate any difference in prostate-cancer-related mortality rates between men screened annually rather than on an 'opportunistic' basis. However, in the world's largest trial to date--the European Randomised Study of Screening for Prostate Cancer--screening every 2-4 years was associated with a 21% reduction in prostate-cancer-related mortality rate after 11 years. Citing the uncertain ratio between potential harm and potential benefit, the US Preventive Services Task Force recently recommended against serum PSA screening. Although this ratio has yet to be elucidated, PSA testing--and early tumour detection--is undoubtedly beneficial for some individuals. Instead of adopting a 'one size fits all' approach, physicians are likely to perform personalized risk assessment to minimize the risk of negative consequences, such as anxiety, unnecessary testing and biopsies, overdiagnosis, and overtreatment. The PSA test needs to be combined with other predictive factors or be used in a more thoughtful way to identify men at risk of symptomatic or life-threatening cancer, without overdiagnosing indolent disease. A risk-adapted approach is needed, whereby PSA testing is tailored to individual risk.

  5. Stroke risk stratification in acute dizziness presentations

    PubMed Central

    Meurer, William J.; Brown, Devin L.; Burke, James F.; Hofer, Timothy P.; Tsodikov, Alexander; Hoeffner, Ellen G.; Fendrick, A.M.; Adelman, Eric E.; Morgenstern, Lewis B.

    2015-01-01

    Objective: To estimate the ability of bedside information to risk stratify stroke in acute dizziness presentations. Methods: Surveillance methods were used to identify patients with acute dizziness and nystagmus or imbalance, excluding those with benign paroxysmal positional vertigo, medical causes, or moderate to severe neurologic deficits. Stroke was defined as acute infarction or intracerebral hemorrhage on a clinical or research MRI performed within 14 days of dizziness onset. Bedside information comprised history of stroke, the ABCD2 score (age, blood pressure, clinical features, duration, and diabetes), an ocular motor (OM)-based assessment (head impulse test, nystagmus pattern [central vs other], test of skew), and a general neurologic examination for other CNS features. Multivariable logistic regression was used to determine the association of the bedside information with stroke. Model calibration was assessed using low (<5%), intermediate (5% to <10%), and high (≥10%) predicted probability risk categories. Results: Acute stroke was identified in 29 of 272 patients (10.7%). Associations with stroke were as follows: ABCD2 score (continuous) (odds ratio [OR] 1.74; 95% confidence interval [CI] 1.20–2.51), any other CNS features (OR 2.54; 95% CI 1.06–6.08), OM assessment (OR 2.82; 95% CI 0.96–8.30), and prior stroke (OR 0.48; 95% CI 0.05–4.57). No stroke cases were in the model's low-risk probability category (0/86, 0%), whereas 9 were in the moderate-risk category (9/94, 9.6%) and 20 were in the high-risk category (20/92, 21.7%). Conclusion: In acute dizziness presentations, the combination of ABCD2 score, general neurologic examination, and a specialized OM examination has the capacity to risk-stratify acute stroke on MRI. PMID:26511453

  6. Epigenetic Testing for Breast Cancer Risk Stratification

    DTIC Science & Technology

    2014-06-01

    no detectable methylation in lymphocytes. As part of this project we obtained RP-FNA samples from Carol Fabian. Dr. Fabian expels her RP-FNA samples...1943. 8. Lewis CM, Cler LR, Bu DW, et al. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk. Clin...American Society of Preventive Oncology. May 2008;17(5):1051-1059. 10. Bu D, Lewis CM, Sarode V, et al. Identification of breast cancer DNA methylation

  7. Applying risk assessment models in non-surgical patients: effective risk stratification.

    PubMed

    Eldor, A

    1999-08-01

    Pulmonary embolism and deep vein thrombosis are serious complications of non-surgical patients, but scarcity of data documenting prophylaxis means antithrombotic therapy is rarely used. Prediction of risk is complicated by the variation in the medical conditions associated with venous thromboembolism (VTE), and lack of data defining risk in different groups. Accurate risk assessment is further confounded by inherited or acquired factors for VTE, additional risk due to medical interventions, and interactions between risk factors. Acquired and inherited risk factors may underlie thromboembolic complications in a range of conditions, including pregnancy, ischaemic stroke, myocardial infarction and cancer. Risk stratification may be feasible in non-surgical patients by considering individual risk factors and their cumulative effects. Current risk assessment models require expansion and modification to reflect emerging evidence in the non-surgical field. A large on-going study of prophylaxis with low-molecular-weight heparin in non-surgical patients will clarify our understanding of the components of risk, and assist in developing therapy recommendations.

  8. Risk stratification after acute myocardial infarction: which studies are best?

    PubMed

    Figueredo, V M

    1996-04-01

    The prognosis for a patient who has survived an acute myocardial infarction depends on three general prognostic factors: (1) residual left ventricular function, (2) remaining viable myocardium at risk (residual ischemia), and (3) presence of substrate for the development of malignant arrhythmias. Multiple clinical and historical factors predict the presence of one or more of these prognostic indicators. Electrocardiographic exercise treadmill testing needs to be done in all patients with uncomplicated infarctions. Guidelines of the American College of Cardiology/American Heart Association Task Force are recommended for risk stratification in most patients after acute myocardial infarction.

  9. Cardiac risk stratification for postmyocardial infarction dental patients.

    PubMed

    Roberts, H W; Mitnitsky, E F

    2001-06-01

    Traditional dental management guidelines of myocardial infarction survivors mandate a 6-month waiting period before elective treatment can be considered. Technological advances in cardiac disease diagnosis, management, and revascularization treatment may make this older mandatory 6-month waiting period obsolete. The purposes of this literature review are to provide an overview of the historical development of cardiac risk stratification and discuss current developments and guidelines in cardiac risk assessment. We hope that this review and update will stimulate the development of updated dental guidelines for treating the cardiac patient.

  10. 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.

  11. Role of risk stratification and genetics in sudden cardiac death.

    PubMed

    Rai, Vikrant; Agrawal, Devendra K

    2017-03-01

    Sudden cardiac death (SCD) is a major public health issue due to its increasing incidence in the general population and the difficulty in identifying high-risk individuals. Nearly 300 000 - 350 000 patients in the United States and 4-5 million patients in the world die annually from SCD. Coronary artery disease and advanced heart failure are the main etiology for SCD. Ischemia of any cause precipitates lethal arrhythmias, and ventricular tachycardia and ventricular fibrillation are the most common lethal arrhythmias precipitating SCD. Pulseless electrical activity, bradyarrhythmia, and electromechanical dissociation also result in SCD. Most SCDs occur outside of the hospital setting, so it is difficult to estimate the public burden, which results in overestimating the incidence of SCD. The insufficiency and limited predictive value of various indicators and criteria for SCD result in the increasing incidence. As a result, there is a need to develop better risk stratification criteria and find modifiable variables to decrease the incidence. Primary and secondary prevention and treatment of SCD need further research. This critical review is focused on the etiology, risk factors, prognostic factors, and importance of risk stratification of SCD.

  12. Early Molecular Stratification of High-risk Primary Biliary Cholangitis.

    PubMed

    Hardie, Claire; Green, Kile; Jopson, Laura; Millar, Ben; Innes, Barbara; Pagan, Sarah; Tiniakos, Dina; Dyson, Jessica; Haniffa, Muzlifah; Bigley, Venetia; Jones, David E; Brain, John; Walker, Lucy J

    2016-12-01

    High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel. Principle component analysis (PCA) demonstrated discrete gene expression clustering between controls and high- and low-risk PBC. High-risk PBC was characterised by up-regulation of genes linked to T-cell activation and apoptosis, INF-γ signalling and leukocyte migration and down-regulation of those linked to the complement pathway. CDKN1a, up-regulated in high-risk PBC, correlated with significantly increased expression of its gene product, the senescence marker p21(WAF1/Cip), by biliary epithelial cells. Our findings suggest high- and low-risk PBC are biologically different from disease outset and senescence an early feature in high-risk disease. Identification of a high-risk 'signal' early from standard FFPE tissue sections has clear clinical utility allowing for patient stratification and second-line therapeutic intervention.

  13. Risk stratification using data from electronic medical records better predicts suicide risks than clinician assessments

    PubMed Central

    2014-01-01

    Background To date, our ability to accurately identify patients at high risk from suicidal behaviour, and thus to target interventions, has been fairly limited. This study examined a large pool of factors that are potentially associated with suicide risk from the comprehensive electronic medical record (EMR) and to derive a predictive model for 1–6 month risk. Methods 7,399 patients undergoing suicide risk assessment were followed up for 180 days. The dataset was divided into a derivation and validation cohorts of 4,911 and 2,488 respectively. Clinicians used an 18-point checklist of known risk factors to divide patients into low, medium, or high risk. Their predictive ability was compared with a risk stratification model derived from the EMR data. The model was based on the continuation-ratio ordinal regression method coupled with lasso (which stands for least absolute shrinkage and selection operator). Results In the year prior to suicide assessment, 66.8% of patients attended the emergency department (ED) and 41.8% had at least one hospital admission. Administrative and demographic data, along with information on prior self-harm episodes, as well as mental and physical health diagnoses were predictive of high-risk suicidal behaviour. Clinicians using the 18-point checklist were relatively poor in predicting patients at high-risk in 3 months (AUC 0.58, 95% CIs: 0.50 – 0.66). The model derived EMR was superior (AUC 0.79, 95% CIs: 0.72 – 0.84). At specificity of 0.72 (95% CIs: 0.70-0.73) the EMR model had sensitivity of 0.70 (95% CIs: 0.56-0.83). Conclusion Predictive models applied to data from the EMR could improve risk stratification of patients presenting with potential suicidal behaviour. The predictive factors include known risks for suicide, but also other information relating to general health and health service utilisation. PMID:24628849

  14. Molecular risk stratification in advanced heart failure patients

    PubMed Central

    Lamirault, Guillaume; Meur, Nolwenn Le; Roussel, Jean-Christian; Cunff, Marie-France Le; Baron, Daniel; Bihouée, Audrey; Guisle, Isabelle; Raharijaona, Mahatsangy; Ramstein, Gérard; Teusan, Raluca; Chevalier, Catherine; Gueffet, Jean-Pierre; Trochu, Jean-Noël; Léger, Jean J; Houlgatte, Rémi; Steenman, Marja

    2010-01-01

    Abstract Risk stratification in advanced heart failure (HF) is crucial for the individualization of therapeutic strategy, in particular for heart transplantation and ventricular assist device implantation. We tested the hypothesis that cardiac gene expression profiling can distinguish between HF patients with different disease severity. We obtained tissue samples from both left (LV) and right (RV) ventricle of explanted hearts of 44 patients undergoing cardiac transplantation or ventricular assist device placement. Gene expression profiles were obtained using an in-house microarray containing 4217 muscular organ-relevant genes. Based on their clinical status, patients were classified into three HF-severity groups: deteriorating (n= 12), intermediate (n= 19) and stable (n= 13). Two-class statistical analysis of gene expression profiles of deteriorating and stable patients identified a 170-gene and a 129-gene predictor for LV and RV samples, respectively. The LV molecular predictor identified patients with stable and deteriorating status with a sensitivity of 88% and 92%, and a specificity of 100% and 96%, respectively. The RV molecular predictor identified patients with stable and deteriorating status with a sensitivity of 100% and 96%, and a specificity of 100% and 100%, respectively. The molecular prediction was reproducible across biological replicates in LV and RV samples. Gene expression profiling has the potential to reproducibly detect HF patients with highest HF severity with high sensitivity and specificity. In addition, not only LV but also RV samples could be used for molecular risk stratification with similar predictive power. PMID:19793385

  15. Autonomic Dysfunction and Risk Stratification Assessed from Heart Rate Pattern

    PubMed Central

    Günther, A; Witte, O.W; Hoyer, D

    2010-01-01

    The modulation of the autonomic nervous system (ANS) under physiological and pathophysiological conditions is in focus of recent research. Many patients with cardio- and cerebrovascular diseases display features of sympathovagal dysregulation. Measuring specific ANS parameters could improve risk stratification. Thus, the early diagnosis of ANS dysfunction in these patients poses a great challenge with high prognostic relevance. The most relevant methods and measures of Heart Rate Variability (HRV) analysis and HRV monitoring will be described in detail in this chapter. The grown importance of these easily obtainable heart rate patterns in stratifying the risk of patients with myocardial infarction and heart failure as well as ischemic stroke will be demonstrated based on recent clinical studies. In order to perspectively improve clinical management of these patients further large scale clinical investigations on the role of ANS dysfunction will be useful. PMID:21258571

  16. 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.

  17. 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

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

    PubMed

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

    2015-05-14

    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.

  19. Cost-effectiveness of various risk stratification methods for asymptomatic ventricular pre-excitation.

    PubMed

    Czosek, Richard J; Anderson, Jeffrey; Cassedy, Amy; Spar, David S; Knilans, Timothy K

    2013-07-15

    Accessory pathways with "high-risk" properties confer a small but potential risk of sudden cardiac death. Pediatric guidelines advocate for either risk stratification or ablation in patients with ventricular pre-excitation but do not advocate specific methodology. We sought to compare the cost of differing risk-stratification methodologies in pediatric patients with ventricular pre-excitation in this single institutional, retrospective cohort study of asymptomatic pediatric patients who underwent risk stratification for ventricular pre-excitation. Institutional methodology consisted of stratification using graded exercise testing (GXT) followed by esophageal testing in patients without loss of pre-excitation and ultimately ablation in high-risk patients or patients who became clinically symptomatic during follow-up. A decision analysis model was used to compare this methodology with hypothetical methodologies using different components of the stratification technique and an "ablate all" method. One hundred and two pediatric patients with asymptomatic ventricular pre-excitation underwent staged risk stratification; 73% of patients were deemed low risk and avoided ablation and the remaining 27% ultimately were successfully ablated. The use of esophageal testing was associated with a 23% (p ≤0.0001) reduction in cost compared with GXT stratification alone and a 48% (p ≤0.0001) reduction compared with the "ablate all" model. GXT as a lone stratification method was also associated with a 15% cost reduction (p ≤0.0001) compared with the "ablate all" method. In conclusion, risk stratification of pediatric patients with asymptomatic ventricular pre-excitation is associated with reduced cost. These outcomes of cost-effectiveness need to be combined with the risks and benefits associated with ablation and risk stratification.

  20. Epidemiological risk stratification of malaria in the Americas.

    PubMed

    Castillo-Salgado, C

    1992-01-01

    During the last years, malaria had a significant increase in Latin America, emerging again as one critical health problem in the Region of the Americas. More than 1.04 million new cases were reported in 1990. This resurgence of malaria needed a comprehensive strategy for its prevention and control. National malaria control programs recognized the epidemiological stratification of malaria as a valuable method to assist them in the recognition of local variations and factors that specifically contribute to the level and intensity of transmission in critical malarious areas. Also it serves as a useful instrument for the selection of needed malaria prevention and control activities. The principal feature of this approach is to provide a dynamic and ongoing process for assessing the epidemiological importance of different risk factors (socio-economic, ecological, organization of health services) in malaria transmission. Health interventions are based on this assessment and are aimed directly at the reduction or elimination of the identified risk factors operating at the local level. Intersectorial co-participation and the integration of malaria programs in local health services are also important aspects of this public health approach.

  1. Risk stratification for kidney sparing procedure in upper tract urothelial carcinoma

    PubMed Central

    Khene, Zine-Eddine; Mathieu, Romain; Kammerer-Jacquet, Solène-Florence; Seisen, Thomas; Roupret, Morgan; Shariat, Shahrokh F.; Peyronnet, Benoit

    2016-01-01

    Risk stratification for kidney sparing procedures (KSP) to treat upper tract urothelial carcinoma (UTUC) is a major issue. A non-systematic Medline/PubMed literature search was performed using the terms “upper tract urothelial carcinoma” with different combinations of keywords to review the current knowledge on this topic. Original articles, reviews and editorials in English language were selected based on their clinical relevance. Available techniques for KSP include segmental ureterectomy and endoscopic resection through a percutaneous or flexible ureteroscopic access. These approaches were traditionally restricted to patients with imperative indications. Current recommendations suggest that selected patients with normal contralateral kidney should also be candidates for such treatments. Modern imaging and endoscopy have improved to accurately stage and grade the tumor while various prognostic clinical factors and biomarkers have been proposed to identify tumor with aggressive features and worse outcomes. Several predictive models using different combinations of such baseline characteristics may help clinicians in clinical decision making. However, risk-adapted based approach that has been proposed in recent guidelines to identify patients who are more likely to benefit from KSP only relies on few clinical and pathological factors. Despite growing understanding of the disease, treatment of UTUC remains challenging. Further efforts and collaborative multicenter studies are mandatory to improve risk stratification to decide and promote optimal KSP in UTUC. These efforts should focus on the integration of promising biomarkers and predictive tools in clinical decision making. PMID:27785428

  2. Implementing system-wide risk stratification approaches: A review of critical success and failure factors.

    PubMed

    Huckel Schneider, Carmen; Gillespie, James A; Wilson, Andrew

    2017-01-01

    Risk stratification has become a widely used tool for linking people identified at risk of health deterioration to the most appropriate evidence-based care. This article systematically reviews recent literature to determine key factors that have been identified as critical enablers and/or barriers to successful implementation of risk stratification tools at a system level. A systematic search found 23 articles and four promising protocols for inclusion in the review, covering the use to 20 different risk stratification tools. These articles reported on only a small fraction of the risk stratification tools used in health systems; suggesting that while the development and statistical validation of risk stratification algorithms is widely reported, there has been little published evaluation of how they are implemented in real-world settings. Controlled studies provided some evidence that the use of risk stratification tools in combination with a care management plan offer patient benefits and that the use of a risk stratification tool to determine components of a care management plan may contribute to reductions in hospital readmissions, patient satisfaction and improved patient outcomes. Studies with the strongest focus on implementation used qualitative and case study methods. Among these, the literature converged on four key areas of implementation that were found to be critical for overcoming barriers to success: the engagement of clinicians and safeguarding equity, both of which address barriers of acceptance; the health system context to address administrative, political and system design barriers; and data management and integration to address logistical barriers.

  3. 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

  4. Population-based genetic risk prediction and stratification for ovarian cancer: views from women at high risk.

    PubMed

    Rahman, Belinda; Meisel, Susanne F; Fraser, Lindsay; Side, Lucy; Gessler, Sue; Wardle, Jane; Lanceley, Anne

    2015-03-01

    There is an opportunity to improve outcomes for ovarian cancer (OC) through advances in risk stratification, early detection and diagnosis. A population-based OC genetic risk prediction and stratification program is being developed. A previous focus group study with individuals from the general population showed support for the proposed program. This qualitative interview study explores the attitudes of women at high risk of OC. Eight women participated in one-on-one, in-depth, semi-structured interviews to explore: experiences of learning of OC risk, risk perceptions, OC knowledge and awareness, and opinions on risk stratification approach. There was evidence of strong support for the proposed program. Benefits were seen as providing reassurance to women at low risk, and reducing worry in women at high risk through appropriate clinical management. Stratification into 'low' and 'high' risk groups was well-received. Participants were more hesitant about stratification to the 'intermediate' risk group. The data suggest formats to effectively communicate OC risk estimates will require careful thought. Interactions with GPs were highlighted as a barrier to OC risk assessment and diagnosis. These results are encouraging for the possible introduction and uptake of a risk prediction and stratification program for OC in the general population.

  5. Feasibility of an automated quantitative computed tomography angiography-derived risk score for risk stratification of patients with suspected coronary artery disease.

    PubMed

    de Graaf, Michiel A; Broersen, Alexander; Ahmed, Wehab; Kitslaar, Pieter H; Dijkstra, Jouke; Kroft, Lucia J; Delgado, Victoria; Bax, Jeroen J; Reiber, Johan H C; Scholte, Arthur J

    2014-06-15

    Coronary computed tomography angiography (CTA) has important prognostic value. Additionally, quantitative CTA (QCT) provides a more detailed accurate assessment of coronary artery disease (CAD) on CTA. Potentially, a risk score incorporating all quantitative stenosis parameters allows accurate risk stratification. Therefore, the purpose of this study was to determine if an automatic quantitative assessment of CAD using QCT combined into a CTA risk score allows risk stratification of patients. In 300 patients, QCT was performed to automatically detect and quantify all lesions in the coronary tree. Using QCT, a novel CTA risk score was calculated based on plaque extent, severity, composition, and location on a segment basis. During follow-up, the composite end point of all-cause mortality, revascularization, and nonfatal infarction was recorded. In total, 10% of patients experienced an event during a median follow-up of 2.14 years. The CTA risk score was significantly higher in patients with an event (12.5 [interquartile range 8.6 to 16.4] vs 1.7 [interquartile range 0 to 8.4], p <0.001). In 127 patients with obstructive CAD (≥50% stenosis), 27 events were recorded, all in patients with a high CTA risk score. In conclusion, the present study demonstrated that a fully automatic QCT analysis of CAD is feasible and can be applied for risk stratification of patients with suspected CAD. Furthermore, a novel CTA risk score incorporating location, severity, and composition of coronary lesion was developed. This score may improve risk stratification but needs to be confirmed in larger studies.

  6. Incorporation of CEA Improves Risk Stratification in Stage II Colon Cancer.

    PubMed

    Spindler, Blake A; Bergquist, John R; Thiels, Cornelius A; Habermann, Elizabeth B; Kelley, Scott R; Larson, David W; Mathis, Kellie L

    2017-03-13

    High-risk features are used to direct adjuvant therapy for stage II colon cancer. Currently, high-risk features are identified postoperatively, limiting preoperative risk stratification. We hypothesized carcinoembryonic antigen (CEA) can improve preoperative risk stratification for stage II colon cancer. The National Cancer Database (NCDB 2004-2009) was reviewed for stage II colon adenocarcinoma patients undergoing curative intent resection. A novel risk stratification including both traditional high-risk features (T4 lesion, <12 lymph nodes sampled, and poor differentiation) and elevated CEA was developed. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. Concordance Probability Estimates (CPE) assessed discrimination. Seventy-four thousand nine hundred forty-five patients were identified; 40,844 (54.5%) had CEA levels reported and were included. Chemotherapy administration was similar between normal and elevated CEA groups (23.8 vs. 25.1%, p = 0.003). Compared to patients with CEA elevation, 5-year overall survival in patients with normal CEA was improved (74.5 vs. 63.4%, p < 0.001). Restratification incorporating CEA resulted in reclassification of 6912 patients (16.9%) from average to high risk. CPE increased for novel risk stratification (0.634 vs. 0.612, SE = 0.005). The routinely available CEA test improved risk stratification for stage II colon cancer. CEA not only may improve staging of colon cancer but may also help guide additional therapy.

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

    PubMed

    Pashayan, Nora; Reisel, Daniel; Widschwendter, Martin

    2016-03-01

    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.

  8. Performance and agreement of risk stratification instruments for postoperative delirium in persons aged 50 years or older.

    PubMed

    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 needed

  9. Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

    PubMed

    Brogan, Richard A; Malkin, Christopher J; Batin, Phillip D; Simms, Alexander D; McLenachan, James M; Gale, Christopher P

    2014-08-26

    Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction (NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention (PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.

  10. Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies.

    PubMed

    Gagnon, J; Lévesque, E; Borduas, F; Chiquette, J; Diorio, C; Duchesne, N; Dumais, M; Eloy, L; Foulkes, W; Gervais, N; Lalonde, L; L'Espérance, B; Meterissian, S; Provencher, L; Richard, J; Savard, C; Trop, I; Wong, N; Knoppers, B M; Simard, J

    2016-12-01

    In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification-unlike those for population screening programs, which are currently well regulated-are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies.

  11. 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

  12. New Methods for the Analysis of Heartbeat Behavior in Risk Stratification

    PubMed Central

    Glass, Leon; Lerma, Claudia; Shrier, Alvin

    2011-01-01

    Developing better methods for risk stratification for tachyarrhythmic sudden cardiac remains a major challenge for physicians and scientists. Since the transition from sinus rhythm to ventricular tachycardia/fibrillation happens by different mechanisms in different people, it is unrealistic to think that a single measure will be adequate to provide a good index for risk stratification. We analyze the dynamical properties of ventricular premature complexes over 24 h in an effort to understand the underlying mechanisms of ventricular arrhythmias and to better understand the arrhythmias that occur in individual patients. Two dimensional density plots, called heartprints, correlate characteristic features of the dynamics of premature ventricular complexes and the sinus rate. Heartprints show distinctive characteristics in individual patients. Based on a better understanding of the natures of transitions from sinus rhythm to sudden cardiac and the mechanisms of arrhythmia prior to cardiac arrest, it should be possible to develop better methods for risk stratification. PMID:22144963

  13. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms

    PubMed Central

    2017-01-01

    Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone. PMID:28028026

  14. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms.

    PubMed

    Rumi, Elisa; Cazzola, Mario

    2017-02-09

    Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone.

  15. 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.

  16. Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies

    PubMed Central

    Gagnon, J.; Lévesque, E.; Borduas, F.; Chiquette, J.; Diorio, C.; Duchesne, N.; Dumais, M.; Eloy, L.; Foulkes, W.; Gervais, N.; Lalonde, L.; L’Espérance, B.; Meterissian, S.; Provencher, L.; Richard, J.; Savard, C.; Trop, I.; Wong, N.; Knoppers, B.M.; Simard, J.

    2016-01-01

    In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification—unlike those for population screening programs, which are currently well regulated—are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies. PMID:28050152

  17. Use of two gene panels for prostate cancer diagnosis and patient risk stratification.

    PubMed

    Xiao, Kefeng; Guo, Jinan; Zhang, Xuhui; Feng, Xiaoyan; Zhang, Heqiu; Cheng, Zhiqiang; Johnson, Heather; Persson, Jenny L; Chen, Lingwu

    2016-08-01

    Currently, no ideal prostate cancer (PCa) diagnostic or prognostic test is available due to the lack of biomarkers with high sensitivity and specificity. There is an unmet medical need to develop combinations of multiple biomarkers which may have higher accuracy in detection of PCa and stratification of aggressive and indolent cancer patients. The aim of this study was to test two biomarker gene panels in distinguishing PCa from benign prostate and high-risk, aggressive PCa from low-risk, indolent PCa, respectively. We identified a five-gene panel that can be used to distinguish PCa from benign prostate. The messenger RNA (mRNA) expression signature of the five genes was determined in 144 PCa and benign prostate specimens from prostatectomy. We showed that the five-gene panel distinguished PCa from benign prostate with sensitivity of 96.59 %, specificity of 92.86 %, and area under the curve (AUC) of 0.992 (p < 0.0001). The five-gene panel was further validated in a 137 specimen cohort and showed sensitivity of 84.62 %, specificity of 91.84 %, and AUC of 0.942 (p < 0.0001). To define subtypes of PCa for treatment guidance, we examined mRNA expression signature of an eight-gene panel in 87 PCa specimens from prostatectomy. The signature of the eight-gene panel was able to distinguish aggressive PCa (Gleason score >6) from indolent PCa (Gleason score ≤6) with sensitivity of 90.28 %, specificity of 80.00 %, and AUC of 0.967 (p < 0.0001). This panel was further validated in a 158 specimen cohort and showed significant difference between aggressive PCa and indolent PCa with sensitivity of 92.57 %, specificity of 70.00 %, and AUC of 0.962 (p < 0.0001). Our findings in assessing multiple biomarkers in combination may provide new tools to detect PCa and distinguish aggressive and indolent PCa for precision and personalized treatment. The two biomarker panels may be used in clinical settings for accurate PCa diagnosis and patient risk stratification

  18. Comparison of dermatoscopic ABCD rule and risk stratification in the diagnosis of malignant melanoma.

    PubMed

    Lorentzen, H; Weismann, K; Kenet, R O; Secher, L; Larsen, F G

    2000-01-01

    For didactic and documentation purposes the dermatoscopic ABCD rule and the dermatoscopic risk stratification have been proposed. The aim of this investigation was to compare the ability of the 2 methods to separate patients with cutaneous malignant melanoma from individuals with other pigmented skin lesions. Three dermatologists, experienced users of dermatoscopy, assessed macroscopic clinical and dermatoscopic slides from 258 patients referred to the skin cancer outpatient clinic by the ABCD rule and risk stratification methods. Diagnostic performance of the 2 methods was compared by receiver operating characteristics curve analysis. When all pigmented skin lesions were compared, there was a trend for the observers to perform better using risk stratification. When only lesions with a well-defined pigment network were included, the diagnostic performance of the risk stratification method was superior to the dermatoscopic ABCD rule (areas under the receiver operating characteristics curve median 0.93 vs. 0.80, p<0.004) for all observers. The agreement between the 2 methods was moderate to substantial (kappa coefficient 0.53-0.62). More melanomas were identified when the rules were combined. The dermatoscopic ABCD rule has been accepted as a standard for identifying melanomas with the dermatoscope, but should be considered secondary to pigment network analysis.

  19. What is the utility of preoperative frailty assessment for risk stratification in cardiac surgery?

    PubMed

    Bagnall, Nigel Mark; Faiz, Omar; Darzi, Ara; Athanasiou, Thanos

    2013-08-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether frailty scoring can be used either separately or combined with conventional risk scores to predict survival and complications. Five hundred and thirty-five papers were found using the reported search, of which nine cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There is a paucity of evidence, as advanced age is a criterion for exclusion in most randomized controlled trials. Conventional models of risk following cardiac surgery are not calibrated to accurately predict the outcomes in the elderly and do not currently include frailty parameters. There is no universally accepted definition for frailty, but it is described as a physiological decline in multiple organ systems, decreasing a patient's capacity to withstand the stresses of surgery and disease. Frailty is manifest clinically as deficits in functional capacity, such as slow ambulation and impairments in the activities of daily living (ADL). Analysis of predictive models using area under receiver operating curves (AUC) suggested only a modest benefit by adding gait speed to a Society of Thoracic Surgeons (STS score)-Predicted Risk of Mortality or Major Morbidity (PROM) risk score (AUC 0.04 mean difference). However, a specialist frailty assessment tool named FORECAST was found to be superior at predicting adverse outcomes at 1 year compared with either EuroSCORE or STS score (AUC 0.09 mean difference). However, risk models incorporating frailty parameters require further validation and have not been widely adopted. Routine collection of objective frailty measures such as 5-metre walk time and ADL assessment will help to provide data to develop new risk-assessment models to facilitate risk stratification and

  20. Multicenter Development and Validation of a Risk Stratification Tool for Ward Patients

    PubMed Central

    Yuen, Trevor C.; Winslow, Christopher; Robicsek, Ari A.; Meltzer, David O.; Gibbons, Robert D.; Edelson, Dana P.

    2014-01-01

    Rationale: Most ward risk scores were created using subjective opinion in individual hospitals and only use vital signs. Objectives: To develop and validate a risk score using commonly collected electronic health record data. Methods: All patients hospitalized on the wards in five hospitals were included in this observational cohort study. Discrete-time survival analysis was used to predict the combined outcome of cardiac arrest (CA), intensive care unit (ICU) transfer, or death on the wards. Laboratory results, vital signs, and demographics were used as predictor variables. The model was developed in the first 60% of the data at each hospital and then validated in the remaining 40%. The final model was compared with the Modified Early Warning Score (MEWS) using the area under the receiver operating characteristic curve and the net reclassification index (NRI). Measurements and Main Results: A total of 269,999 patient admissions were included, with 424 CAs, 13,188 ICU transfers, and 2,840 deaths occurring during the study period. The derived model was more accurate than the MEWS in the validation dataset for all outcomes (area under the receiver operating characteristic curve, 0.83 vs. 0.71 for CA; 0.75 vs. 0.68 for ICU transfer; 0.93 vs. 0.88 for death; and 0.77 vs. 0.70 for the combined outcome; P value < 0.01 for all comparisons). This accuracy improvement was seen across all hospitals. The NRI for the electronic Cardiac Arrest Risk Triage compared with the MEWS was 0.28 (0.18–0.38), with a positive NRI of 0.19 (0.09–0.29) and a negative NRI of 0.09 (0.09–0.09). Conclusions: We developed an accurate ward risk stratification tool using commonly collected electronic health record variables in a large multicenter dataset. Further study is needed to determine whether implementation in real-time would improve patient outcomes. PMID:25089847

  1. Mortality Risk Stratification in Fontan Patients Who Underwent Heart Transplantation.

    PubMed

    Berg, Christopher J; Bauer, Brenton S; Hageman, Abbie; Aboulhosn, Jamil A; Reardon, Leigh C

    2017-03-01

    The number of patients who require orthotopic heart transplantation (OHT) for failing Fontan physiology continues to grow; however, the methods and tools to evaluate risk of OHT are limited. This study aimed to identify a set of preoperative variables and characteristics that were associated with a greater risk of postoperative mortality in patients who received OHT for failing Fontan physiology. Thirty-six Fontan patients were identified as having undergone OHT at University of California-Los Angeles Medical Center from 1991 to 2014. Data were collected retrospectively and analyzed. The primary end point was designated as postoperative mortality. After an average follow-up time of 3.5 years, 17 (44%) patients suffered postoperative mortality. Patient characteristics including (1) age <18 years at the time of OHT, (2) Fontan-OHT interval of <10 years, (3) systemic ventricular ejection fraction <20%, (4) moderate-to-severe atrioventricular valve insufficiency, (5) an elevated Model of End-stage Liver Disease, eXcluding INR score, or (6) need for advanced mechanical support before surgery were associated with an increased incidence of postoperative mortality. Using these risk factors, we present a theoretical framework to stratify risk of postoperative death in failing Fontan patients after OHT. In conclusion, a method such as this may aid in the transplantation evaluation and listing process of patients with failing Fontan physiology.

  2. Raynaud’s phenomenon and digital ischemia: a practical approach to risk stratification, diagnosis and management

    PubMed Central

    McMahan, Zsuzsanna H.; Wigley, Fredrick M.

    2015-01-01

    Digital ischemia is a painful and often disfiguring event. Such an ischemic event often leads to tissue loss and can significantly affect the patient’s quality of life. Digital ischemia can be secondary to a vasculopathy, vasculitis, embolic disease, trauma, or extrinsic vascular compression. It is an especially serious complication in patients with scleroderma. Risk stratification of patients with scleroderma at risk for digital ischemia is now possible with clinical assessment and autoantibody profiles. Because there are a variety of conditions that lead to digital ischemia, it is important to understand the pathophysiology underlying each ischemic presentation in order to target therapy appropriately. Significant progress has been made in the last two decades in defining the pathophysiological processes leading to digital ischemia in rheumatic diseases. In this article we review the risk stratification, diagnosis, and management of patients with digital ischemia and provide a practical approach to therapy, particularly in scleroderma. PMID:26523153

  3. 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

  4. 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

  5. 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

  6. Risk stratification and selection for statin therapy: going beyond Framingham.

    PubMed

    Fitchett, David H; Mancini, G B John; Gregoire, Jean; Anderson, Todd; McPherson, Ruth

    2014-06-01

    Decisions for statin therapy in the primary prevention of atherosclerotic cardiovascular disease are generally made using the 10-year Framingham Risk Score (FRS). Even when a family history of premature cardiovascular disease is taken into account, there is often ambiguity about the need for statin therapy for patients with a 10-year FRS of 5%-19% and low-density lipoprotein cholesterol <3.5 mmol/L. Current Canadian dyslipidemia guidelines recommend consideration of a diversity of other factors, including biochemical measurements and imaging studies to help determine whether the calculated FRS might be misleadingly low and whether statin therapy might, therefore, be prudent. However, efficient use of the plethora of secondary factors makes this decision process itself potentially ambiguous. This brief summary provides a practical approach for using clinical information, basic biochemical tests, and more specialized tests, such as carotid ultrasound and coronary artery calcium scoring, to identify groups of patients at greater risk for atherosclerotic cardiovascular disease than suggested by the FRS.

  7. Analytical and assay issues for use of cardiac troponin testing for risk stratification in primary care.

    PubMed

    Wu, Alan H B; Christenson, Robert H

    2013-08-01

    Cardiac troponin is the standard marker for diagnosis of acute myocardial infarction and risk stratification of patients who present to an emergency department with signs and symptoms of acute cardiac ischemia. Over the past few years, the analytical sensitivity of assays for cardiac troponin has improved significantly to the point where a detectable amount of troponin can be measured in essentially all healthy subjects. Recent studies have shown that use of a highly sensitive troponin assays may provide value to traditional markers of primary disease risk for patients, i.e., for those who have no history of heart disease. There are barriers to the adoption of cardiac troponin for screening high risk cohorts such as the elderly, diabetics and perhaps even the asymptomatic population. Strategies used for the assignment of cutoff concentrations in acute care, i.e., the 99 th percentile, may not be appropriate for primary care as changes over baseline levels may provide more accurate information of risk than cross-sectional results. A review of biological variation has shown that cardiac troponin as a biomarker has low index of individuality, indicating that reference values are of little utility. Whether or not cardiac troponin can be released in reversible injury is a debate that could have significance for detecting minor myocardial injury. A major hurdle for use of troponin in primary care is the lack of assay standardization and nomenclature for the different generations of troponin assays. Standardization requires knowledge of what is released after cardiac injury and what the various cardiac troponin assays are measuring. Currently it is not clear if the cardiac troponin release after ischemic injury is identical to that in circulation of healthy individuals. This may affect the design of future assays and standardization approaches. There is potential that a marker of myocardial injury such as troponin can add to the value of existing indicators and biomarkers

  8. Stratification, competition and risk distribution: health insurance in Germany and the United States.

    PubMed

    Abel, T; Wysong, J A

    1992-01-01

    Issues of unequal risk distribution among sickness funds are given increasing attention in the current discussions on the reform of the statutory health insurance system in Germany. This paper examines the structural determinants of risk distribution and points toward the links between social stratification, competition, health risk and insurance status. A model showing the links between basic structural determinants is presented. Using health survey data from Germany and the U.S., statistical analyses are conducted. The results support the model and indicate its applicability for both health care systems. The paper concludes by indicating the relevance of such findings for health policy and future research.

  9. 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

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

    PubMed

    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.

  11. Risk stratification for sudden cardiac death in North America - current perspectives.

    PubMed

    Buxton, Alfred E; Waks, Jonathan W; Shen, Changyu; Chen, Peng-Sheng

    Sudden cardiac death (SCD) accounts for approximately 360,000 deaths annually in the United States, and is the cause of half of all cardiovascular deaths. In patients with severely depressed left ventricular ejection fraction (LVEF), implantable cardioverter-defibrillators (ICDs) have been shown to significantly reduce total mortality, but many factors beyond LVEF influence the relative benefit afforded by ICD implantation. In fact, among patients with prior myocardial infarction, approximately half of all SCDs occur in patients without severe LV dysfunction, and in analyses of large ICD trials, certain patient subgroups derive no benefit to ICD implantation despite having low LVEF, often due to competing non-arrhythmic mortality. Improved risk stratification tools to help select patients who are likely to derive the most benefit from ICD implantation are therefore needed. This manuscript will review studies evaluating use of ICDs in patients with mild LV systolic dysfunction and LVEF >35%, currently available ICD risk stratification models, and the rationale for designing a cohort study to prospectively validate use of an ICD risk stratification score.

  12. Probabilistic Modeling Of Ocular Biomechanics In VIIP: Risk Stratification

    NASA Technical Reports Server (NTRS)

    Feola, A.; Myers, J. G.; Raykin, J.; Nelson, E. S.; Mulugeta, L.; Samuels, B.; Ethier, C. R.

    2016-01-01

    the peak strains, we ranked and then normalized these coefficients, considering that normalized values 0.5 implied a substantial influence on the range of the peak strains in the optic nerve head (ONH). IOP and ICP were found to have a major influence on the peak strains in the ONH, as did optic nerve and LC stiffness. Interestingly, the stiffness of the sclera far from the scleral canal did not have a large influence on peak strains in ONH tissues; however, the collagen fiber stiffness in the peripapillary sclera and annular ring both influenced the peak strains within the ONH. We have created a physiologically relevant model that incorporated collagen fibers to study the effects of elevated ICP. Elevated ICP resulted in strains in the optic nerve that are not predicted to occur on earth: the upright or supine conditions. We found that IOP, ICP, lamina cribrosa stiffness and optic nerve stiffness had the highest association with these extreme strains in the ONH. These extreme strains may activate mechanosensitive cells that induce tissue remodeling and are a risk factor for the development of VIIP.

  13. 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

  14. Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients.

    PubMed

    Jons, Christian; O-Uchi, Jin; Moss, Arthur J; Reumann, Matthias; Rice, John J; Goldenberg, Ilan; Zareba, Wojciech; Wilde, Arthur A M; Shimizu, Wataru; Kanters, Jorgen K; McNitt, Scott; Hofman, Nynke; Robinson, Jennifer L; Lopes, Coeli M B

    2011-03-30

    Inherited long QT syndrome (LQTS) is caused by mutations in ion channels that delay cardiac repolarization, increasing the risk of sudden death from ventricular arrhythmias. Currently, the risk of sudden death in individuals with LQTS is estimated from clinical parameters such as age, gender, and the QT interval, measured from the electrocardiogram. Even though a number of different mutations can cause LQTS, mutation-specific information is rarely used clinically. LQTS type 1 (LQT1), one of the most common forms of LQTS, is caused by mutations in the slow potassium current (I(Ks)) channel α subunit KCNQ1. We investigated whether mutation-specific changes in I(Ks) function can predict cardiac risk in LQT1. By correlating the clinical phenotype of 387 LQT1 patients with the cellular electrophysiological characteristics caused by an array of mutations in KCNQ1, we found that channels with a decreased rate of current activation are associated with increased risk of cardiac events (hazard ratio=2.02), independent of the clinical parameters usually used for risk stratification. In patients with moderate QT prolongation (a QT interval less than 500 ms), slower activation was an independent predictor for cardiac events (syncope, aborted cardiac arrest, and sudden death) (hazard ratio = 2.10), whereas the length of the QT interval itself was not. Our results indicate that genotype and biophysical phenotype analysis may be useful for risk stratification of LQT1 patients and suggest that slow channel activation is associated with an increased risk of cardiac events.

  15. 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

  16. Simplified risk score models accurately predict the risk of major in-hospital complications following percutaneous coronary intervention.

    PubMed

    Resnic, F S; Ohno-Machado, L; Selwyn, A; Simon, D I; Popma, J J

    2001-07-01

    The objectives of this analysis were to develop and validate simplified risk score models for predicting the risk of major in-hospital complications after percutaneous coronary intervention (PCI) in the era of widespread stenting and use of glycoprotein IIb/IIIa antagonists. We then sought to compare the performance of these simplified models with those of full logistic regression and neural network models. From January 1, 1997 to December 31, 1999, data were collected on 4,264 consecutive interventional procedures at a single center. Risk score models were derived from multiple logistic regression models using the first 2,804 cases and then validated on the final 1,460 cases. The area under the receiver operating characteristic (ROC) curve for the risk score model that predicted death was 0.86 compared with 0.85 for the multiple logistic model and 0.83 for the neural network model (validation set). For the combined end points of death, myocardial infarction, or bypass surgery, the corresponding areas under the ROC curves were 0.74, 0.78, and 0.81, respectively. Previously identified risk factors were confirmed in this analysis. The use of stents was associated with a decreased risk of in-hospital complications. Thus, risk score models can accurately predict the risk of major in-hospital complications after PCI. Their discriminatory power is comparable to those of logistic models and neural network models. Accurate bedside risk stratification may be achieved with these simple models.

  17. 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

  18. 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

  19. 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

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

    PubMed

    Ciampi, Quirino; Villari, Bruno

    2007-10-02

    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.

  1. Prognostic value of cardiac biomarkers in the risk stratification of syncope: a systematic review.

    PubMed

    Thiruganasambandamoorthy, Venkatesh; Ramaekers, Rosa; Rahman, Mohammed Omair; Stiell, Ian Gilmour; Sikora, Lindsey; Kelly, Sarah-Louise; Christ, Michael; Claret, Pierre-Geraud; Reed, Matthew James

    2015-12-01

    The role of cardiac biomarkers in risk stratification of syncope is unclear. We undertook a systematic review to assess their predictive value for short-term major adverse cardiovascular events (MACE). We conducted a systematic review using MEDLINE, EMBASE, DARE and Cochrane databases from inception to July 2014. We included studies involving adult syncope patients that evaluated cardiac biomarker levels for risk stratification during acute management and excluded case reports, reviews and studies involving children. Primary outcome (MACE) included death, cardiopulmonary resuscitation, myocardial infarction (MI), structural heart disease, pulmonary embolism, significant hemorrhage or cardiac procedural interventions. Secondary outcome analysis assessed for prediction of MI, cardiac syncope and death. Two reviewers extracted patient-level data based on the cut-off reported. Pooled sensitivities and specificities were calculated using patient-level data. A total of 1862 articles were identified, and 11 studies with 4246 patients were included. Studies evaluated 3 biomarkers: contemporary troponin (2693 patients), natriuretic peptides (1353 patients) and high-sensitive troponin (819 patients). The pooled sensitivities and specificities for MACE were: contemporary troponin 0.29 (95 % CI 0.24, 0.34) and 0.88 (95 % CI 0.86, 0.89); natriuretic peptides 0.77 (95 % CI 0.69, 0.85) and 0.73 (95 % CI 0.70, 0.76); high-sensitive troponin 0.74 (95 % CI 0.65, 0.83) and 0.65 (95 % CI 0.62, 0.69), respectively. Natriuretic peptides and high-sensitive troponin showed good diagnostic characteristics for both primary and secondary outcomes. Natriuretic peptides and high-sensitive troponin might be useful in risk stratification.

  2. Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment.

    PubMed

    Dalle, Jean-Hugues; Giralt, Sergio A

    2016-03-01

    Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), can develop in a subset of patients, primarily after myeloablative hematopoietic stem cell transplantation, but it also may occur after reduced-intensity conditioning. Severe VOD/SOS, typically characterized by multiorgan failure, has been associated with a mortality rate greater than 80%. Therefore, an accurate and prompt diagnosis of VOD/SOS is essential for early initiation of appropriate therapy to improve clinical outcomes. Moreover, some studies have support the use of prophylaxis for patients who are at high risk of developing VOD/SOS. This review summarizes risk factors associated with development of VOD/SOS, including pretransplantation patient characteristics and factors related to stem cell transplantation, that can facilitate patient stratification according to risk. The incidence of VOD/SOS, clinical features, and diagnostic criteria are reviewed. Data on emerging treatment strategies for patients with VOD/SOS are discussed in the context of recent treatment guidelines. Additionally, options for prophylaxis in individuals who are at increased risk are presented. Although historically only those patients with moderate to severe VOD/SOS have been treated, early therapy and prophylaxis may be appropriate for many patients and may have the potential to improve patients' outcomes and survival, including for those with nonsevere disease.

  3. 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

  4. Establishment and Application of Early Risk Stratification Method for Acute Abdominal Pain in Adults

    PubMed Central

    Wang, Yu; Zhao, Hong; Zhou, Zhen; Tian, Ci; Xiao, Hong-Li; Wang, Bao-En

    2017-01-01

    Background: Acute abdominal pain is a common symptom of emergency patients. The severity was always evaluated based on physicians’ clinical experience. The aim of this study was to establish an early risk stratification method (ERSM) for addressing adults with acute abdominal pain, which would guide physicians to take appropriate and timely measures following the established health-care policies. Methods: In Cohort 1, the records of 490 patients with acute abdominal pain that developed within the past 72 h were enrolled in this study. Measurement data and numeration data were compared with analysis of variance and Chi-square test, respectively. Multiple regression analysis calculated odd ratio (OR) value. P and OR values showed the impacts of factors. ERSM was established by clinical experts and statistical experts according to Youden index. In Cohort 2, data from 305 patients with acute abdominal pain were enrolled to validate the accuracy of the ERSM. Then, ERSM was prospectively used in clinical practice. Results: The ERSM was established based on the scores of the patient's clinical characteristics: right lower abdominal pain + 3 × diffuse abdominal pain + 3 × cutting abdominal pain + 3 × pain frequency + 3 × pain duration + fever + 2 × vomiting + 5 × stop defecation + 3 × history of abdominal surgery + hypertension history + diabetes history + hyperlipidemia history + pulse + 2 × skin yellowing + 2 × sclera yellowing + 2 × double lung rale + 10 × unconsciousness + 2 × right lower abdominal tenderness + 5 × diffuse abdominal tenderness + 4 × peritoneal irritation + 4 × bowel sounds abnormal + 10 × suspicious diagnosis + white blood cell count + hematocrit + glucose + 2 × blood urea nitrogen + 3 × creatine + 4 × serum albumin + alanine aminotransferase + total bilirubin + 3 × conjugated bilirubin + amylase. When the score was <18, the patient did not need hospitalization. A score of ≥18 and <38 indicated that the patient should be under

  5. Pulmonary embolism risk stratification by European Society of Cardiology is associated with recurrent venous thromboembolism: Findings from a long-term follow-up study.

    PubMed

    Zhang, Shuai; Zhai, Zhenguo; Yang, Yuanhua; Zhu, Jianguo; Kuang, Tuguang; Xie, Wanmu; Yang, Suqiao; Liu, Fangfang; Gong, Juanni; Shen, Ying H; Wang, Chen

    2016-01-01

    Venous thromboembolism (VTE) recurrence carries significant mortality and morbidity. Accurate risk assessment and effective treatment for patients with acute pulmonary embolism (PE) is important for VTE recurrence prevention. We examined the association of VTE recurrence with risk stratification and PE treatment. We enrolled 627 patients with a first episode of confirmed PE. Baseline clinical information was collected. PE severity was assessed by the European Society of Cardiology's (ESC) risk stratification, the simplified PE Severity Index (sPESI) and the Qanadli score of clot burden. Patients were followed for 1-5 years. The cumulative recurrent VTE and all-cause death were documented. The association between recurrent VTE and risk factors was analyzed. The cumulative incidences of recurrent VTE were 4.5%, 7.3%, and 13.9% at 1, 2, and 5 years of follow-up, respectively. The VTE recurrence was associated with higher (high- and intermediate-) risk stratification predicted by ESC model (HR 1.838, 95% CI 1.318-2.571, P<0.001), as well as with unprovoked PE (HR 2.809, 95% CI 1.650-4.781, P b 0.001) and varicose veins (HR 4.747, 95% CI 2.634-8.557, P<0.001). The recurrence was negatively associated with longer (≥6 months) anticoagulation (HR 0.473, 95% CI 0.285-0.787, P=0.004), especially in patients with higher risk (HR 0.394, 95% CI 0.211-0.736, P=0.003) and unprovoked PE (HR 0.248, 95% CI 0.122-0.504, P<0.001). ESC high-risk and intermediate-risk PE, unprovoked PE and varicose veins increase recurrence risk. Longer anticoagulation treatment reduces recurrence, especially in higher risk and unprovoked PE patients.

  6. Risk Stratification for Athletes and Adventurers in High-Altitude Environments: Recommendations for Preparticipation Evaluation.

    PubMed

    Campbell, Aaron D; McIntosh, Scott E; Nyberg, Andy; Powell, Amy P; Schoene, Robert B; Hackett, Peter

    2015-12-01

    High-altitude athletes and adventurers face a number of environmental and medical risks. Clinicians often advise participants or guiding agencies before or during these experiences. Preparticipation evaluation (PPE) has the potential to reduce risk of high-altitude illnesses in athletes and adventurers. Specific conditions susceptible to high-altitude exacerbation also important to evaluate include cardiovascular and lung diseases. Recommendations by which to counsel individuals before participation in altitude sports and adventures are few and of limited focus. We reviewed the literature, collected expert opinion, and augmented principles of a traditional sport PPE to accommodate the high-altitude wilderness athlete/adventurer. We present our findings with specific recommendations on risk stratification during a PPE for the high-altitude athlete/adventurer.

  7. 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.

  8. 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

  9. Selectively predictive calcium supplementation using NCCN risk stratification system after thyroidectomy with differentiated thyroid cancer

    PubMed Central

    Sun, Ronghao; Zhang, Jie; Zhang, Fenghua; Fan, Jinchuan; Yuan, Ying; Li, Chao

    2015-01-01

    Background: Hypocalcemia is a common complication following thyroidectomy. To explore reasonable and simple methods for predicting postoperative hypocalcemia and identify the optimal strategies for selective calcium supplement are meaningful for surgeon. Methods: Based on the NCCN risk stratification system, patients were divided into 4 groups (A-D): low-risk group A, who only underwent limited thyroidectomy (LT) and high-risk groups B, C and D, who had received total thyroidectomy (TT) and selective central and/or lateral neck dissection (SND). After surgery, group C patients were orally given calcium gluconate and group D patients were intravenously given calcium 2 g/day for 7 days, while group B patients did not receive any calcium supplement. Serum calcium and parathyroid hormone (PTH) levels were collected before and after surgery. The incidence of asymptomatic and symptomatic hypocalcemia in each group was recorded. Results: A total of 132 patients with differentiated thyroid carcinoma (DTC) were included who received surgical treatment. No a significant change was observed in serum calcium and PTH levels in group A, while significant decreases in serum calcium and PTH levels were seen in group B (P < 0.05). Intravenous calcium supplement in group D resulted in a more rapid recovery in serum calcium levels (P < 0.05). The incidences of symptomatic hypocalcemia and asymptomatic hypocalcemia were significantly lower in group A and group D respectively compared to the other groups (All P values < 0.05). In group B, a highest asymptomatic and symptomatic hypocalcemia incidence was detected. Conclusion: Selective calcium supplementation for DTC based on NCCN risk stratification system could be recommended for the high-risk patients. PMID:26885165

  10. 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.

  11. Drug-induced liver injury: Towards early prediction and risk stratification

    PubMed Central

    Raschi, Emanuel; De Ponti, Fabrizio

    2017-01-01

    Drug-induced liver injury (DILI) is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications and agents listed as causing liver damage (http://livertox.nih.gov/). As it was the case in the past decade with drug-induced QT prolongation/arrhythmia, there is an urgent unmet clinical need to develop tools for risk assessment and stratification in clinical practice and, in parallel, to improve prediction of pre-clinical models to support regulatory steps and facilitate early detection of liver-specific adverse drug events. Although drug discontinuation and therapy reconciliation still remain the mainstay in patient management to minimize occurrence of DILI, especially acute liver failure events, different multidisciplinary attempts have been proposed in 2016 to predict and assess drug-related risk in individual patients; these promising, albeit preliminary, results strongly support the need to pursue this innovative pathway. PMID:28105256

  12. 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

  13. SIOP‐PODC adapted risk stratification and treatment guidelines: Recommendations for neuroblastoma in low‐ and middle‐income settings

    PubMed Central

    Howard, Scott C.; Chantada, Guillermo; Israels, Trijn; Khattab, Mohammed; Alcasabas, Patricia; Lam, Catherine G.; Faulkner, Lawrence; Park, Julie R.; London, Wendy B.; Matthay, Katherine K.

    2015-01-01

    Neuroblastoma is the most common extracranial solid tumor in childhood in high‐income countries (HIC), where consistent treatment approaches based on clinical and tumor biological risk stratification have steadily improved outcomes. However, in low‐ and middle‐ income countries (LMIC), suboptimal diagnosis, risk stratification, and treatment may occur due to limited resources and unavailable infrastructure. The clinical practice guidelines outlined in this manuscript are based on current published evidence and expert opinions. Standard risk stratification and treatment explicitly adapted to graduated resource settings can improve outcomes for children with neuroblastoma by reducing preventable toxic death and relapse. Pediatr Blood Cancer 2015;62:1305–1316. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc. PMID:25810263

  14. Carotid ultrasound in the cardiovascular risk stratification of patients with rheumatoid arthritis: when and for whom?

    PubMed

    González-Gay, Miguel A; González-Juanatey, Carlos; Llorca, Javier

    2012-06-01

    Adequate stratification of cardiovascular (CV) risk is one of the major points of interest in the management of patients with rheumatoid arthritis (RA). A task force of the European League Against Rheumatism has proposed to adapt CV risk management calculated in RA patients according to the systematic coronary risk evaluation (SCORE) function by application of a multiplier factor of 1.5 in those patients with two of the following three criteria: disease duration >10 years, rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibody positivity, and presence of severe extra-articular manifestations. However, a major concern when using the modified SCORE is to know whether the effect of chronic inflammation on the CV risk of RA patients can be fully determined using this tool. As increased carotid intima-media thickness (IMT) and carotid plaques have been proved to predict the development of CV events in RA, the authors suggest performing carotid ultrasound when SCORE does not yield results indicating high CV risk in RA patients with extra-articular manifestations, RF or anti-CCP positivity as well as in patients with 10 years disease duration or longer. The presence of abnormal carotid IMT (>0.90 mm) or carotid plaques would lead to these patients being considered as having high CV risk regardless of the results derived from the modified SCORE.

  15. 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

  16. 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.

  17. Foresight begins with FMEA. Delivering accurate risk assessments.

    PubMed

    Passey, R D

    1999-03-01

    If sufficient factors are taken into account and two- or three-stage analysis is employed, failure mode and effect analysis represents an excellent technique for delivering accurate risk assessments for products and processes, and for relating them to legal liability. This article describes a format that facilitates easy interpretation.

  18. Risk stratification in motor area-related glioma surgery based on navigated transcranial magnetic stimulation data.

    PubMed

    Rosenstock, Tizian; Grittner, Ulrike; Acker, Güliz; Schwarzer, Vera; Kulchytska, Nataliia; Vajkoczy, Peter; Picht, Thomas

    2017-04-01

    OBJECTIVE Navigated transcranial magnetic stimulation (nTMS) is a noninvasive method for preoperatively localizing functional areas in patients with tumors in presumed motor eloquent areas. The aim of this study was to establish an nTMS-based risk stratification model by examining whether the results of nTMS mapping and its neurophysiological data predict postoperative motor outcome in glioma surgery. METHODS Included in this study were prospectively collected data for 113 patients undergoing bihemispheric nTMS examination prior to surgery for gliomas in presumed motor eloquent locations. Multiple ordinal logistic regression analysis was performed to test for any association between preoperative nTMS-related variables and postoperative motor outcome. RESULTS A new motor deficit or deterioration due to a preexisting deficit was observed in 20% of cases after 7 days and in 22% after 3 months. In terms of tumor location, no new permanent deficit was observed when the distance between tumor and corticospinal tract was greater than 8 mm and the precentral gyrus was not infiltrated (p = 0.014). New postoperative deficits on Day 7 were associated with a pathological excitability of the motor cortices (interhemispheric resting motor threshold [RMT] ratio < 90% or > 110%, p = 0.031). Interestingly, motor function never improved when the RMT was significantly higher in the tumorous hemisphere than in the healthy hemisphere (RMT ratio > 110%). CONCLUSIONS The proposed risk stratification model, based on objective functional-anatomical and neurophysiological measures, enables one to counsel patients about the risk of functional deterioration or the potential for recovery.

  19. Pulmonary embolism: the diagnosis, risk-stratification, treatment and disposition of emergency department patients

    PubMed Central

    Corrigan, Daniel; Prucnal, Christiana; Kabrhel, Christopher

    2016-01-01

    The diagnosis or exclusion of pulmonary embolism (PE) remains challenging for emergency physicians. Symptoms can be vague or non-existent, and the clinical presentation shares features with many other common diagnoses. Diagnostic testing is complicated, as biomarkers, like the D-dimer, are frequently false positive, and imaging, like computed tomography pulmonary angiography, carries risks of radiation and contrast dye exposure. It is therefore incumbent on emergency physicians to be both vigilant and thoughtful about this diagnosis. In recent years, several advances in treatment have also emerged. Novel, direct-acting oral anticoagulants make the outpatient treatment of low risk PE easier than before. However, the spectrum of PE severity varies widely, so emergency physicians must be able to risk-stratify patients to ensure the appropriate disposition. Finally, PE response teams have been developed to facilitate rapid access to advanced therapies (e.g., catheter directed thrombolysis) for patients with high-risk PE. This review will discuss the clinical challenges of PE diagnosis, risk stratification and treatment that emergency physicians face every day. PMID:27752629

  20. Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques.

    PubMed

    Zannad, Faiez; De Backer, Guy; Graham, Ian; Lorenz, Matthias; Mancia, Giuseppe; Morrow, David A; Reiner, Zeljko; Koenig, Wolfgang; Dallongeville, Jean; Macfadyen, Robert J; Ruilope, Luis M; Wilhelmsen, Lars

    2012-04-01

    The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A(2) , genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

  1. Genetic Stratification to Identify Risk Groups for Alzheimer’s Disease

    PubMed Central

    Marioni, Riccardo E.; Campbell, Archie; Hagenaars, Saskia P.; Nagy, Reka; Amador, Carmen; Hayward, Caroline; Porteous, David J.; Visscher, Peter M.; Deary, Ian J.

    2017-01-01

    Stratification by genetic risk factors for Alzheimer’s disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60–70 years (subset n = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus. Additive and multiplicative effects of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta –0.04, p = 0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes (p = 0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5% of the distribution) show cognitive decrements, albeit much smaller than for APOE ɛ4ɛ4 compared to ɛ3ɛ3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD. PMID:28222519

  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. Psychosis Prediction: Stratification of Risk Estimation With Information-Processing and Premorbid Functioning Variables

    PubMed Central

    Nieman, Dorien H.; Ruhrmann, Stephan; Dragt, Sara; Soen, Francesca; van Tricht, Mirjam J.; Koelman, Johannes H. T .M.; Bour, Lo J; Velthorst, Eva; Becker, Hiske E.; Weiser, Mark; Linszen, Don H.; de Haan, Lieuwe

    2014-01-01

    Background: The period preceding the first psychotic episode is regarded as a promising period for intervention. We aimed to develop an optimized prediction model of a first psychosis, considering different sources of information. The outcome of this model may be used for individualized risk estimation. Methods: Sixty-one subjects clinically at high risk (CHR), participating in the Dutch Prediction of Psychosis Study, were assessed at baseline with instruments yielding data on neuropsychology, symptomatology, environmental factors, premorbid adjustment, and neurophysiology. The follow-up period was 36 months. Results: At 36 months, 18 participants (29.5%) had made a transition to psychosis. Premorbid adjustment (P = .001, hazard ratio [HR] = 2.13, 95% CI = 1.39/3.28) and parietal P300 amplitude (P = .004, HR = 1.27, 95% CI = 1.08/1.45) remained as predictors in the Cox proportional hazard model. The resulting prognostic score (PS) showed a sensitivity of 88.9% and a specificity of 82.5%. The area under the curve of the PS was 0.91 (95% CI = 0.83–0.98, cross-validation: 0.86), indicating an outstanding ability of the model to discriminate between transition and nontransition. The PS was further stratified into 3 risk classes establishing a prognostic index. In the class with the worst social-personal adjustment and lowest P300 amplitudes, 74% of the subjects made a transition to psychosis. Furthermore, transition emerged on average more than 17 months earlier than in the lowest risk class. Conclusions: Our results suggest that predicting a first psychotic episode in CHR subjects could be improved with a model including premorbid adjustment and information-processing variables in a multistep algorithm combining risk detection and stratification. PMID:24142369

  4. [Diagnosis, sudden death risk stratification, and treatment of main long QT syndrome molecular-genetic variants].

    PubMed

    Shkol'nikova, M A; Kharlap, M S; Il'darova, R A; Bereznitskaia, V V; Kalinin, L A

    2011-01-01

    Inherited long QT syndrome (LQTS) refers to the primary electrical diseases of the heart. It is characterized by QT prolongation on resting ECG and syncope due to life-threatening ventricular arrhythmias. This review focuses on diagnosis, differential diagnosis, risk stratification of sudden cardiac death, and treatment strategy of patients with most prevalent genetic fOrms of LQTS - LQT1, LQT2 and LQT3, which accounted for about 90% of all genetically confirmed cases. Recent advances in understanding of relationship between clinical, electrocardiographic features (on ECG, body surface mapping, stress test) and genetic variants of LQT presented. Characteristics of syncopal events and ECG features of LQTl, LQT2 and LQT3 in the majority of cases are helpful to make an appropriate choice for therapy, even before positive result of molecular genetic testing. Management has focused on the use of beta blockers as first-line treatment and exclusion of triggers of life-threatening arrhythmia which are specific for each molecular-genetic variant. Implantation of cardioverter defibrillator for secondary prevention of sudden death in the high-risk patients or patients with insufficient effect of antiarrhythmic therapy is required.

  5. 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.

  6. Chronic heart failure in the elderly: value of cardiopulmonary exercise testing in risk stratification

    PubMed Central

    Davies, L; Francis, D; Piepoli, M; Scott, A; Ponikowski, P; Coats, A

    2000-01-01

    OBJECTIVE—To assess the value of cardiopulmonary exercise testing in predicting prognosis in a cohort of elderly patients with chronic heart failure (CHF).
DESIGN—A retrospective cohort study of all patients with CHF over the age of 70 years assessed between January 1992 and May 1997.
SETTING—Tertiary centre.
PATIENTS—50 patients (mean (SD) age 75.9 (4.5) years, 8 women) with CHF New York Heart Association (NYHA) class I (3 patients), II (25 patients), III (20 patients), and IV (2 patients). Follow up was complete for two years in all patients.
RESULTS—The patients underwent cardiopulmonary exercise testing (peak oxygen consumption 15.2 (4.5) ml/kg/min, minute ventilation/carbon dioxide production (VE/VCO2) slope 38.7 (11.8)); radionucleide ventriculography (left ventricular ejection fraction 32.8 (14.3)%); serum sodium measurement (139 (2.8) mmol/l); and echocardiography (left ventricular end diastolic dimension 6.1 (1.1) cm, left ventricular end systolic dimension 4.7 (1.5) cm). At the end of follow up in May 1999, 26 patients had died. The median follow up of the survivors was 47.7 months (interquartile range 31.5-53.5 months). On univariate analysis VE/VCO2 slope (p < 0.0001), NYHA class (p < 0.001), peak oxygen uptake (VO2) (p < 0.01), left ventricular end systolic dimension (p < 0.05), and serum sodium concentration (p < 0.05) had significant predictive power. Stepwise multivariate analysis identified only VE/VCO2 slope (p < 0.01), NYHA class (p < 0.05), and peak VO2 (p< 0.05) as conveying significant independent prognostic information.
CONCLUSION—Elderly patients with CHF have a high mortality, with the majority dead within two years. Cardiopulmonary exercise testing provides important information for risk stratification within this group and its use should not be neglected.


Keywords: cardiopulmonary exercise testing; chronic heart failure; elderly patients; risk factor stratification PMID

  7. Multiparametric analysis of heart rate variability used for risk stratification among survivors of acute myocardial infarction.

    PubMed

    Voss, A; Hnatkova, K; Wessel, N; Kurths, J; Sander, A; Schirdewan, A; Camm, A J; Malik, M

    1998-01-01

    A multiparametric heart rate variability analysis was performed to prove if combined heart rate variability (HRV) measures of different domains improve the result of risk stratification in patients after myocardial infarction. In this study, standard time domain, frequency domain and non-linear dynamics measures of HRV assessment were applied to 572 survivors of acute myocardial infarction. Three parameter sets each consisting of 4 parameters were applied and compared with the standard measurement of global heart rate variability HRVi. Discriminant analysis technique and t-test were performed to separate the high risk groups from the survivors. The predictive value of this approach was evaluated with receiver operator (ROC) and positive predictive accuracy (PPA) curves. Results--The discriminant analysis shows a separation of patients suffered by all cause mortality in 80% (best single parameter 74%) and sudden arrhythmic death in 86% (73%). All parameters of set 1 show a high significant difference (p < 0.001) between survivors and non-survivors based on two-tailed t-test. The specificity level of the multivariate parameter sets is at the 70% sensitivity level (ROC) about 85-90%, whereas HRVi shows maximum levels of 70%. The PPA in the all cause mortality group is at the 70% sensitivity level twice as high as the univariate HRV measure and increases to more than fourfold as high within the VT/VF group. In conclusion, in this population, the multiparametric approach with the combination of four parameters from all domains especially from NLD seems to be a better predictor of high arrhythmia risk than the standard measurement of global heart rate variability.

  8. 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.

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

    PubMed Central

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

    2014-01-01

    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

  10. The incremental value of brachial flow-mediated dilation measurements in risk stratification for incident cardiovascular events: a systematic review.

    PubMed

    Peters, Sanne A E; den Ruijter, Hester M; Bots, Michiel L

    2012-06-01

    Abstract Adequate risk assessment for cardiovascular disease (CVD) is essential as a guide to initiate drug treatment. Current methods based on traditional risk factors could be improved considerably. Although brachial flow-mediated dilation (FMD) predicts subsequent cardiovascular events, its predictive value on top of traditional risk factors is unknown. We performed a systematic review to evaluate the incremental predictive value of FMD on top of traditional risk factors in asymptomatic individuals. Using PubMed and reference tracking, three studies were identified that reported on the incremental value of FMD using change in the area under the curve (AUC). Two large cohort studies found no improvement in AUC when FMD was added to traditional risk prediction models, whereas one small case-control study found an improvement. One study used the net reclassification improvement (NRI) to assess whether FMD measurement leads to correct risk stratification in risk categories. Although this study did not find an improvement in AUC, the NRI was statistically significant. Based on the reclassification results of this study, FMD measurement might be helpful in risk prediction. Evidence supporting the use of FMD measurement in clinical practice for risk stratification for CVD on top of traditional risk factors is limited, and future studies are needed.

  11. Analysis of agreement between cardiac risk stratification protocols applied to participants of a center for cardiac rehabilitation

    PubMed Central

    Santos, Ana A. S.; Silva, Anne K. F.; Vanderlei, Franciele M.; Christofaro, Diego G. D.; Gonçalves, Aline F. L.; Vanderlei, Luiz C. M.

    2016-01-01

    ABSTRACT Background Cardiac risk stratification is related to the risk of the occurrence of events induced by exercise. Despite the existence of several protocols to calculate risk stratification, studies indicating that there is similarity between these protocols are still unknown. Objective To evaluate the agreement between the existing protocols on cardiac risk rating in cardiac patients. Method The records of 50 patients from a cardiac rehabilitation program were analyzed, from which the following information was extracted: age, sex, weight, height, clinical diagnosis, medical history, risk factors, associated diseases, and the results from the most recent laboratory and complementary tests performed. This information was used for risk stratification of the patients in the protocols of the American College of Sports Medicine, the Brazilian Society of Cardiology, the American Heart Association, the protocol designed by Frederic J. Pashkow, the American Association of Cardiovascular and Pulmonary Rehabilitation, the Société Française de Cardiologie, and the Sociedad Española de Cardiología. Descriptive statistics were used to characterize the sample and the analysis of agreement between the protocols was calculated using the Kappa coefficient. Differences were considered with a significance level of 5%. Results Of the 21 analyses of agreement, 12 were considered significant between the protocols used for risk classification, with nine classified as moderate and three as low. No agreements were classified as excellent. Different proportions were observed in each risk category, with significant differences between the protocols for all risk categories. Conclusion The agreements between the protocols were considered low and moderate and the risk proportions differed between protocols. PMID:27556385

  12. Anomalous Coronary Arteries and Myocardial Bridges: Risk Stratification in Children Using Novel Cardiac Catheterization Techniques.

    PubMed

    Agrawal, Hitesh; Molossi, Silvana; Alam, Mahboob; Sexson-Tejtel, S Kristen; Mery, Carlos M; McKenzie, E Dean; Fraser, Charles D; Qureshi, Athar M

    2017-02-18

    The evaluation of the vast majority of children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridges is performed with non-invasive testing. However, a subset of these patients may benefit from invasive testing for risk stratification. All patients included in the Coronary Anomalies Program (CAP) at Texas Children's Hospital who underwent cardiac catheterization were included. Techniques included selective coronary angiograms (SCA), intravascular ultrasound (IVUS), and fractional flow reserve (FFR) measurements with provocative testing using adenosine and/or dobutamine infusions. Out of the 131 patients followed by the CAP between 12/12-4/16, 8 (6%) patients underwent 9 cath investigations at median age 13.1 (2.6-18.7) years and median weight 49.5 (11.4-142.7) kg. Six patients presented with cardiac signs/symptoms. Four patients had myocardial bridges of the left anterior descending (LAD) coronary artery, 2 patients had isolated AAOCA, and 2 patients had an anomalous left coronary artery (LCA) with an intramyocardial course of the LAD. SCA was performed in all patients. FFR was positive in 4/6 patients: IVUS showed >70% intraluminal narrowing in 3/5 patients. One patient had hemodynamic instability that reversed with catheter removal from the coronary ostium. Based on the catheterization data obtained, findings were reassuring in three patients, surgery was performed in three patients, and two patients are being medically managed/restricted from competitive sports. In our small cohort of patients, we demonstrated that IVUS and FFR can safely be performed in children and may help to risk stratify some patients with AAOCA and myocardial bridges.

  13. Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management

    PubMed Central

    2014-01-01

    Background and hypothesis Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. Objective and method To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. Results (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. Conclusions The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps

  14. Arrhythmia Phenotype during Fetal Life Suggests LQTS Genotype: Risk Stratification of Perinatal Long QT Syndrome

    PubMed Central

    Cuneo, Bettina F.; Etheridge, Susan P.; Horigome, Hitoshi; Sallee, Denver; Moon-Grady, Anita; Weng, Hsin-Yi; Ackerman, Michael J.; Benson, D. Woodrow

    2014-01-01

    Background Fetal arrhythmias characteristic of long QT syndrome (LQTS) include torsades de pointes (TdP) and/or 2° atrioventricular block (AVB), but sinus bradycardia, defined as fetal heart rate <3% for gestational age, is most common. We hypothesized that prenatal rhythm phenotype might predict LQTS genotype and facilitate improved risk stratification and management. Method and Results Records of subjects exhibiting LQTS fetal arrhythmias were reviewed. Fetal echocardiograms, neonatal ECG, and genetic testing were evaluated. We studied 43 subjects exhibiting fetal LQTS arrhythmias: TdP ± 2° AVB (Group 1, n=7), isolated 2° AVB (Group 2, n=4) and sinus bradycardia (Group 3, n=32). Mutations in known LQTS genes were found in 95% of subjects tested. SCN5A mutations occurred in 71% of Group 1 while 91% of subjects with KCNQ1 mutations were in Group 3. Small numbers of subjects with KCNH2 mutations (n=4) were scattered in all 3 groups. Age at presentation did not differ among groups, and most subjects (n=42) were live born with gestational ages of 37.5±2.8 wks (mean±SD). However, those with TdP were typically delivered earlier. Prenatal treatment in Group 1 terminated (n=2) or improved (n=4) TdP. The neonatal QTc (mean±SE) of Group 1 (664.7±24.9) was longer than neonatal QTc in both Group 2 (491.2±27.6, p=0.004) and Group 3 (483.1±13.7, p<0.001). Despite medical and pacemaker therapy, postnatal cardiac arrest (n=4) or sudden death (n=1) was common among subjects with fetal/neonatal TdP. Conclusions Rhythm phenotypes of fetal LQTS have genotype-suggestive features which, along with QTc duration, may risk stratify perinatal management. PMID:23995044

  15. 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

  16. The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study

    PubMed Central

    Hausfater, Pierre; Amin, Devendra; Amin, Adina; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Conca, Antoinette; Haubitz, Sebastian; Struja, Tristan; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2016-01-01

    Introduction The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. Methods We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. Results Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75–1.5nmol/L, >1.5nmol/L, p ANOVA <0.0001). Risk stratification by combining ProADM within cut-off groups and the triage score resulted in the identification of 1662 patients (25.2% of the population) at a very low risk of mortality (0.3%, n = 5) and 425 patients (6.5% of the population) at very high risk of mortality (19.3%, n = 82). Risk estimation by using ProADM and the triage score from a logistic regression model allowed for a more accurate risk estimation in the whole population with a classification of 3255 patients (49.4% of the population) in the low risk group (0.3% mortality, n = 9) and 1673 (25.4% of the population) in the high-risk group (15.1% mortality, n = 252). Conclusions Within this large international multicenter study, a combined triage score based on ProADM and established triage scores allowed a more accurate mortality risk discrimination. The TRIAGE-ProADM score improved identification of both patients at the highest risk of mortality who may benefit from early therapeutic interventions (rule in), and low risk patients where deferred treatment without negatively affecting outcome may be possible (rule out). PMID:28005916

  17. Stroke Risk Stratification and its Validation using Ultrasonic Echolucent Carotid Wall Plaque Morphology: A Machine Learning Paradigm.

    PubMed

    Araki, Tadashi; Jain, Pankaj K; Suri, Harman S; Londhe, Narendra D; Ikeda, Nobutaka; El-Baz, Ayman; Shrivastava, Vimal K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Gupta, Ajay; Suri, Jasjit S

    2017-01-01

    Stroke risk stratification based on grayscale morphology of the ultrasound carotid wall has recently been shown to have a promise in classification of high risk versus low risk plaque or symptomatic versus asymptomatic plaques. In previous studies, this stratification has been mainly based on analysis of the far wall of the carotid artery. Due to the multifocal nature of atherosclerotic disease, the plaque growth is not restricted to the far wall alone. This paper presents a new approach for stroke risk assessment by integrating assessment of both the near and far walls of the carotid artery using grayscale morphology of the plaque. Further, this paper presents a scientific validation system for stroke risk assessment. Both these innovations have never been presented before. The methodology consists of an automated segmentation system of the near wall and far wall regions in grayscale carotid B-mode ultrasound scans. Sixteen grayscale texture features are computed, and fed into the machine learning system. The training system utilizes the lumen diameter to create ground truth labels for the stratification of stroke risk. The cross-validation procedure is adapted in order to obtain the machine learning testing classification accuracy through the use of three sets of partition protocols: (5, 10, and Jack Knife). The mean classification accuracy over all the sets of partition protocols for the automated system in the far and near walls is 95.08% and 93.47%, respectively. The corresponding accuracies for the manual system are 94.06% and 92.02%, respectively. The precision of merit of the automated machine learning system when compared against manual risk assessment system are 98.05% and 97.53% for the far and near walls, respectively. The ROC of the risk assessment system for the far and near walls is close to 1.0 demonstrating high accuracy.

  18. 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.

  19. BRAF V600E and risk stratification of thyroid microcarcinoma: a multicenter pathological and clinical study.

    PubMed

    Tallini, Giovanni; de Biase, Dario; Durante, Cosimo; Acquaviva, Giorgia; Bisceglia, Michele; Bruno, Rocco; Bacchi Reggiani, Maria Letizia; Casadei, Gian Piero; Costante, Giuseppe; Cremonini, Nadia; Lamartina, Livia; Meringolo, Domenico; Nardi, Francesco; Pession, Annalisa; Rhoden, Kerry J; Ronga, Giuseppe; Torlontano, Massimo; Verrienti, Antonella; Visani, Michela; Filetti, Sebastiano

    2015-10-01

    Studies from single institutions have analyzed BRAF in papillary microcarcinomas, sometimes with contradictory results. Most of them have provided limited integration of histological and clinical data. To obtain a comprehensive picture of BRAF V600E-mutated microcarcinomas and to evaluate the role of BRAF testing in risk stratification we performed a retrospective multicenter analysis integrating microscopical, pathological, and clinical information. Three hundred and sixty-five samples from 300 patients treated at six medical institutions covering different geographical regions of Italy were analyzed with central review of all cases. BRAF V600E statistical analysis was conducted on 298 microcarcinomas from 264 patients after exclusion of those that did not meet the required criteria. BRAF V600E was identified in 145/298 tumors (49%) including the following subtypes: 35/37 (95%, P<0.0001) tall cell and 72/114 (64%, P<0.0001) classic; conversely 94/129 follicular variant papillary microcarcinomas (73%, P<0.0001) were BRAF wild type. BRAF V600E-mutated microcarcinomas were characterized by markedly infiltrative contours (P<0.0001) with elongated strings of neoplastic cells departing from the tumor, and by intraglandular tumor spread (P<0.0001), typically within 5 mm of the tumor border. Multivariate analysis correlated BRAF V600E with specific microscopic features (nuclear grooves, optically clear nuclei, tall cells within the tumor, and tumor fibrosis), aggressive growth pattern (infiltrative tumor border, extension into extrathyroidal tissues, and intraglandular tumor spread), higher American Thyroid Association recurrence risk group, and non-incidental tumor discovery. The following showed the strongest link to BRAF V600E: tall cell subtype, many neoplastic cells with nuclear grooves or with optically clear nuclei, infiltrative growth, intraglandular tumor spread, and a tumor discovery that was non-incidental. BRAF V600E-mutated microcarcinomas represent a

  20. Procedures for risk-stratification of lung cancer using buccal nanocytology.

    PubMed

    Subramanian, H; Viswanathan, P; Cherkezyan, L; Iyengar, R; Rozhok, S; Verleye, M; Derbas, J; Czarnecki, J; Roy, H K; Backman, V

    2016-09-01

    Lung cancer is the leading cause of cancer deaths in the U.S. with survival dramatically depending on stage at diagnosis. We had earlier reported that nanocytology of buccal cells can accurately risk-stratify smokers for the presence of early and late-stage lung cancer. To translate the technique into clinical practice, standardization of operating procedures is necessary to consistently yield precise and repeatable results. Here, we develop and validate simple, robust, and easily implementable procedures for specimen collection, processing, etc. in addition to a commercially-viable instrument prototype. Results of this work enable translation of the technology from academic lab to physicians' office.

  1. Procedures for risk-stratification of lung cancer using buccal nanocytology

    PubMed Central

    Subramanian, H.; Viswanathan, P.; Cherkezyan, L.; Iyengar, R.; Rozhok, S.; Verleye, M.; Derbas, J.; Czarnecki, J.; Roy, H. K.; Backman, V.

    2016-01-01

    Lung cancer is the leading cause of cancer deaths in the U.S. with survival dramatically depending on stage at diagnosis. We had earlier reported that nanocytology of buccal cells can accurately risk-stratify smokers for the presence of early and late-stage lung cancer. To translate the technique into clinical practice, standardization of operating procedures is necessary to consistently yield precise and repeatable results. Here, we develop and validate simple, robust, and easily implementable procedures for specimen collection, processing, etc. in addition to a commercially-viable instrument prototype. Results of this work enable translation of the technology from academic lab to physicians’ office. PMID:27699138

  2. Risk Stratification Model to Detect Early Pulmonary Disease in Infants With Cystic Fibrosis Diagnosed by Newborn Screening

    PubMed Central

    Britton, Lacrecia J.; Oates, Gabriela R.; Oster, Robert A.; Self, Staci T.; Troxler, Robert B.; Hoover, Wynton C.; Gutierrez, Hector H.; Harris, William T.

    2017-01-01

    Summary Objective The clinical benefit of newborn screening (NBS) for cystic fibrosis (CF) has been primarily nutritional, with less overt respiratory impact. Identification of risk factors for infant CF lung disease could facilitate targeted interventions to improve pulmonary outcomes. Methods This retrospective study evaluated socioeconomic information, clinical data, and results from routine infant pulmonary function testing (iPFT) of infants diagnosed with CF through NBS (N = 43) at a single CF center over a 4-year period (2008–2012). A five-item composite clinical score was developed and combined with socioeconomic indicators to facilitate identification of CF infants at increased risk of early-onset respiratory impairment. Results Paternal education was positively associated with lung function (P = 0.02). Clinical score <7 (on a scale of 0–10) predicted diminished pulmonary measure (P < 0.005). Retrospective risk stratification by clinical score and paternal education identified CF infants at low, intermediate, or high risk of pulmonary disease. Forced expiratory volume (FEV0.5%, mean ± SD) averaged 115 ± 19% in the low-risk group, 97 ± 17% in the intermediate-risk group, and 90 ± 8% in the high-risk group (P < 0.005). Results were similar for mid-expiratory flows (FEF25–75%). Multiple regression analysis confirmed the predictive value of this risk stratification model of CF infant pulmonary health. Conclusion We combined socioeconomic and clinical data to risk-stratify CF infants for early-onset lung disease as quantified by iPFT. Our model showed significant differences in infant pulmonary function across risk groups. The developed tool offers an easily available, inexpensive, and non-invasive way to assess risk of respiratory decline in CF infants and identify those meriting targeted therapeutic attention. PMID:27556254

  3. Use of risk stratification to guide ambulatory management of neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee.

    PubMed

    Worth, L J; Lingaratnam, S; Taylor, A; Hayward, A M; Morrissey, S; Cooney, J; Bastick, P A; Eek, R W; Wei, A; Thursky, K A

    2011-01-01

    Utilization of risk-stratification tools in the setting of neutropenic fever is currently limited by inadequate knowledge and lack of awareness. Within this context, the approach to management of low-risk patients with neutropenic fever is inconsistent with the available evidence across many Australian treating centres. These clinical guidelines define and clarify an accepted standard of care for this patient group given the current evidence base. The Multinational Association for Supportive Care in Cancer risk index is presented as the preferred risk assessment tool for determining patient risk. Suitability of ambulatory care within specific patient populations is discussed, with defined eligibility criteria provided to guide clinical decision-making. Detailed recommendations for implementing appropriate ambulatory strategies, such as early discharge and outpatient antibiotic therapy, are also provided. Due consideration is given to infrastructural requirements and other supportive measures at a resourcing and operational level. An analysis of the relevant health economics is also presented.

  4. The Role of Cardiac MRI in the Diagnosis and Risk Stratification of Hypertrophic Cardiomyopathy

    PubMed Central

    Maron, Martin S

    2016-01-01

    Hypertrophic cardiomyopathy (HCM), the most common genetic cardiomyopathy, is a disease characterised by substantial heterogeneity. Although the majority of patients with HCM remain asymptomatic with near-normal longevity, a small, but important, subset remain at risk for a wide range of clinical outcomes including sudden death. Cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as an imaging modality particularly well suited to characterise the phenotypic expression of HCM. CMR helps in the diagnosis of HCM by identifying areas of hypertrophy not well visualised by echocardiography, providing more accurate wall thickness measurements and differentiating HCM from other causes of left ventricular (LV) hypertrophy. CMR has led to the identification of novel subgroups of patients with HCM, including those with LV apical aneurysms (a subgroup at increased risk for ventricular arrhythmias and thromboembolic stroke), as well as abnormalities that contribute to LV outflow obstruction. Additionally, contrast-enhanced CMR with late-gadolinium enhancement (LGE) has recognised patients with extensive LGE (≥15 % LV myocardium) as individuals who may be at increased risk of sudden death, independent of other high-risk features, with implications on management strategies including consideration for primary prevention implantable cardioverter defibrillator therapy. These observations justify an expanded role of CMR in the routine clinical assessment of patients with HCM. PMID:28116085

  5. 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

  6. 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

  7. Coronary CT and the Coronary Calcium Score, the Future of ED Risk Stratification?

    PubMed Central

    Fernandez-Friera, Leticia; Garcia-Alvarez, Ana; Guzman, Gabriela; Garcia, Mario J

    2012-01-01

    Accurate and efficient evaluation of acute chest pain remains clinically challenging because traditional diagnostic modalities have many limitations. Recent improvement in non-invasive imaging technologies could potentially improve both diagnostic efficiency and clinical outcomes of patients with acute chest pain while reducing unnecessary hospitalizations. However, there is still controversy regarding much of the evidence for these technologies. This article reviews the role of coronary artery calcium score and the coronary computed tomography in the assessment of individual coronary risk and their usefulness in the emergency department in facilitating appropriate disposition decisions. The evidence base and clinical applications for both techniques are also described, together with cost- effectiveness and radiation exposure considerations. PMID:22708911

  8. The influence of preoperative risk stratification on fast-tracking patients after pulmonary resection.

    PubMed

    Bryant, Ayesha S; Cerfolio, Robert J

    2008-02-01

    Fast-tracking protocols or postoperative care computerized algorithms have been shown to reduce hospital length of stay and reduce costs; however, not all patients can be fast-tracked. Certain patient characteristics may put patients at increased risk to fail fast-tracking. Additionally some patients have multiple risk factors that have an additive effect that puts them at an even increased risk to fail fast-tracking, and more importantly, to significant morbidity. It is a mistake to force these protocols on all patients because it can lead to increased complications, readmissions, and low patient and family satisfaction. By carefully analyzing surgical results via accurate prospective databases, the types of patients who fail fast-tracking and the reasons they fail can be identified. Once these characteristics are pinpointed, specific changes to the postoperative algorithm can be implemented, and these alterations can lead to improved outcomes. The authors have shown that by using pain pumps instead of epidurals in elderly patients we can improve outcomes and still fast-track octogenarians with minimal morbidity and high-patient satisfaction. We have also shown that the increased use of physical therapy and respiratory treatments (important parts of the care of all patients after pulmonary resection, but a limited resource in most hospitals) may also lead to improved surgical results for those who have low FEV1% and DLco%. Further studies are needed. Although fast-tracking protocols cannot be applied to all, the vast majority of patients who undergo elective pulmonary resection, even those at high risk, can undergo safe, efficient, and cost-saving care via preset postoperative algorithms. When the typical daily events are convened each morning and the planned date of discharge is frequently communicated with the patient and family before surgery and each day in the hospital, most patients can be safely fast-tracked with high satisfaction and outstanding results.

  9. Clinical utility of genetic signatures in selecting adjuvant treatment: Risk stratification for early vs. late recurrences.

    PubMed

    Hayes, Daniel F

    2015-11-01

    Adjuvant endocrine therapy (ET) reduces the odds of distant recurrence and mortality by nearly one-half in women with hormone receptor (HR) positive early stage breast cancer. While the risk of recurrence is lower for HR positive than negative patients during the first 5-7 years, HR positive patients suffer ongoing recurrences between 0.5 and 2% year over subsequent years. Extended adjuvant ET further reduces recurrence during this late phase of follow-up. ET is associated with post-menopausal side effects (hot flashes, sexual dysfunction, mood changes, and weight gain), and occasional major toxicities (thrombosis and endometrial cancer with tamoxifen; bone mineral loss and possibly heart disease with AIs) persist throughout therapy. Accurate and reliable estimates of the risk of recurrence after five years of ET for women with prior HR positive breast cancer would permit appropriate extended ET decisions. The risk of long-term relapse is related to lymph node status and size of tumor, but these are relatively crude. Several groups have investigated whether multi-parameter tumor biomarker tests might identify those patients whose risk of recurrence is so low that extended ET is not justified. These assays include IHC4, the 21-gene "OncotypeDX", the 12-gene "Endopredict," the PAM50, and the 2-gene "Breast Cancer Index (BCI)" assays. The clinical validity of all these tests for this use context have been established, with at least one paper for each that shows a statistically significant difference in risk of distant recurrence during the 5-10 years after the initial five years of adjuvant endocrine therapy. However, the stakes are high, and although each of these represents a "prospective retrospective" study, they require further validation in subsequent datasets before they should be considered to have "clinical utility" and are used to withhold potentially life-saving treatment. Perhaps more importantly, the clinical breast cancer community, and especially the

  10. New ventures require accurate risk analyses and adjustments.

    PubMed

    Eastaugh, S R

    2000-01-01

    For new business ventures to succeed, healthcare executives need to conduct robust risk analyses and develop new approaches to balance risk and return. Risk analysis involves examination of objective risks and harder-to-quantify subjective risks. Mathematical principles applied to investment portfolios also can be applied to a portfolio of departments or strategic business units within an organization. The ideal business investment would have a high expected return and a low standard deviation. Nonetheless, both conservative and speculative strategies should be considered in determining an organization's optimal service line and helping the organization manage risk.

  11. Cardiac Health Risk Stratification System (CHRiSS): a Bayesian-based decision support system for left ventricular assist device (LVAD) therapy.

    PubMed

    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.

  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. Diagnostic evaluation of people with hypertension in low income country: cohort study of “essential” method of risk stratification

    PubMed Central

    Montalvo, Gregorio; Anselmi, Mariella; Prandi, Rosanna; Ibarra, Samuel; Marquez, Monica; Armani, Daniela; Moreira, Juan-Martín; Caicedo, Cynthia; Roncaglioni, Maria Carla; Colombo, Fabio; Camisasca, Paola; Milani, Valentina; Quimì, Simon; Gonzabay, Felix; Tognoni, Gianni

    2008-01-01

    Objectives To explore the predictive power of a risk stratification method for people with hypertension based on “essential” procedures (that is, available in economically less developed areas of the world), comparing it in the same population with the results given by the method suggested by the 1999 World Health Organization-International Society of Hypertension (WHO-ISH) guidelines. Design Prospective cohort study of outcomes according to cardiovascular risk profile at baseline. Setting Primary care in a poor rural area of the Ecuadorian forest. Participants 504 people with hypertension prospectively monitored for a mean of 6.7 (SD 2.3) years. Interventions Essential data included blood pressure, medical history, smoking, age, sex, and diagnosis of diabetes; the WHO-ISH methods additionally included measurement of fasting blood glucose, total cholesterol, and creatinine, urinalysis, and electrocardiography. Main outcome measures Cardiovascular events and total deaths. Results With both methods there was a highly significant association between the level of predicted risk and the incidence of cardiovascular events and of total deaths: up to three quarters of all cardiovascular events and two thirds of all deaths were reported among people classified as at high or very high risk with either method. The predictive discrimination of the essential method is comparable with the WHO-ISH with C statistics (95% confidence interval) of 0.788 (0.721 to 0.855) and 0.744 (0.673 to 0.815), respectively, for cardiovascular events and 0.747 (0.678 to 0.816) and 0.705 (0.632 to 0.778) for total mortality. Conclusions The risk stratification of patients with hypertension with an essential package of variables (that is, available and practicable even in the economically less developed areas of the world) serves at least as well as the more comprehensive method proposed by WHO-ISH. PMID:18805835

  14. 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.

  15. Stratification systems as prognostic tools for defining risk of lymph node metastasis in penile squamous cell carcinomas.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-05-01

    Inguinal lymph node metastasis is the single most important factor for predicting survival in patients with penile squamous cell carcinomas. To estimate the likelihood of this event, investigators have combined pathologic features of the primary tumor in the form of stratification systems. In this article we review 3 such systems (Solsona et al, J Urol 2001;165:1506; Hungerhuber et al, Urology 68:621, 2006; and Chaux et al, Am J Surg Pathol 2009;33:1049) built upon histologic grade, extent and depth of tumor invasion, and perineural invasion. We evaluate their usefulness, limitations, and possible implications for the management of patients with penile cancer. We also provide clues for the proper identification and interpretation of these pathologic features. Inguinal metastases were observed in 64% to 83% of patients in high-risk groups, 20% to 33% of intermediate groups, and 0% to 8% of low-risk groups. The results of these studies suggest that patients in high-risk groups could benefit from prophylactic bilateral groin dissection. In addition, patients in low-risk groups might be managed by surveillance alone. Finally, the authors suggest that additional approaches, such as sentinel lymph node biopsy, should be used for the intermediate-risk group. The identification of other pathologic features, such as vascular and perineural invasion, could tip the scales in problematic or paradoxical cases. The fate of these risk groups would be better defined by the identification of molecular biomarkers and genetic profiling.

  16. Enhancing risk stratification for use in integrated care: a cluster analysis of high-risk patients in a retrospective cohort study

    PubMed Central

    Vuik, Sabine I; Mayer, Erik; Darzi, Ara

    2016-01-01

    Objective To show how segmentation can enhance risk stratification tools for integrated care, by providing insight into different care usage patterns within the high-risk population. Design A retrospective cohort study. A risk score was calculated for each person using a logistic regression, which was then used to select the top 5% high-risk individuals. This population was segmented based on the usage of different care settings using a k-means cluster analysis. Data from 2008 to 2011 were used to create the risk score and segments, while 2012 data were used to understand the predictive abilities of the models. Setting and participants Data were collected from administrative data sets covering primary and secondary care for a random sample of 300 000 English patients. Main measures The high-risk population was segmented based on their usage of 4 different care settings: emergency acute care, elective acute care, outpatient care and GP care. Results While the risk strata predicted care usage at a high level, within the high-risk population, usage varied significantly. 4 different groups of high-risk patients could be identified. These 4 segments had distinct usage patterns across care settings, reflecting different levels and types of care needs. The 2008–2011 usage patterns of the 4 segments were consistent with the 2012 patterns. Discussion Cluster analyses revealed that the high-risk population is not homogeneous, as there exist 4 groups of patients with different needs across the care continuum. Since the patterns were predictive of future care use, they can be used to develop integrated care programmes tailored to these different groups. Conclusions Usage-based segmentation augments risk stratification by identifying patient groups with different care needs, around which integrated care programmes can be designed. PMID:27993905

  17. Recent biologic and genetic advances in neuroblastoma: Implications for diagnostic, risk stratification, and treatment strategies.

    PubMed

    Newman, Erika A; Nuchtern, Jed G

    2016-10-01

    Neuroblastoma is an embryonic cancer of neural crest cell lineage, accounting for up to 10% of all pediatric cancer. The clinical course is heterogeneous ranging from spontaneous regression in neonates to life-threatening metastatic disease in older children. Much of this clinical variance is thought to result from distinct pathologic characteristics that predict patient outcomes. Consequently, many research efforts have been focused on identifying the underlying biologic and genetic features of neuroblastoma tumors in order to more clearly define prognostic subgroups for treatment stratification. Recent technological advances have placed emphasis on the integration of genetic alterations and predictive biologic variables into targeted treatment approaches to improve patient survival outcomes. This review will focus on these recent advances and the implications they have on the diagnostic, staging, and treatment approaches in modern neuroblastoma clinical management.

  18. The use of adenosine and adenosine triphosphate testing in the diagnosis, risk stratification and management of patients with syncope: current evidence and future perspectives.

    PubMed

    Fragakis, Nikolaos; Antoniadis, Antonios P; Saviano, Massimo; Vassilikos, Vassilios; Pappone, Carlo

    2015-03-15

    Syncope is a significant source of cardiovascular-related morbidity yet the etiology is frequently obscure and the identification of patients at highest risk is challenging. Adenosine (AD) and adenosine triphosphate (ATP) administrations have been suggested as potentially useful non-invasive tools in the diagnostic workup of patients with neurally-mediated or bradycardia-related syncope. It has been postulated that both compounds by modulating the autonomic innervation in the heart and exerting negative chronotropic and dromotropic effects in the conduction system, may unmask the mechanism of syncope. However, the clinical implications derived from the efficacy of both tests in the investigation of syncope remain unclear mainly due to inconclusive and occasionally contradictory results of published studies. This review article summarizes recent and past information in the use of ATP and AD in the investigation of syncope with emphasis on clinical trials. We present the current level of evidence for the use of these agents in clinical practice, identify areas where further research is warranted and highlight the future perspectives of these agents as complements to an accurate risk-stratification of patients with syncope.

  19. Cardiac Magnetic Resonance-Verified Myocardial Fibrosis in Chagas Disease: Clinical Correlates and Risk Stratification

    PubMed Central

    Uellendahl, Marly; de Siqueira, Maria Eduarda Menezes; Calado, Eveline Barros; Kalil-Filho, Roberto; Sobral, Dário; Ribeiro, Clébia; Oliveira, Wilson; Martins, Silvia; Narula, Jagat; Rochitte, Carlos Eduardo

    2016-01-01

    Background Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score. Methods This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score. Results Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76). Conclusions CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD. PMID:27982271

  20. Integrating clinical trial findings into practice through risk stratification: the case of heart failure management.

    PubMed

    Smith, David H; Johnson, Eric S; Thorp, Micah L; Crispell, Kathy A; Yang, Xiuhai; Petrik, Amanda F

    2010-06-01

    Heart failure case management programs have been shown in clinical trials to be highly effective at preventing future hospitalizations. But the absolute benefits of these programs depend on the baseline risk of outcome in the treated population. Because baseline risks of hospitalization in trials are often higher than community-based samples, translating trial results to the community setting may be misleading. One solution is to identify subgroups for intervention that have sufficiently high baseline risk. Using estimates of hospitalizations averted from a previously published systematic review of heart failure management, we estimated a program's efficiency based on level of predicted risk. Medical history and demographic data on heart failure patients from a large integrated US health plan were used to build a logistic regression-based prognostic risk score for cardiovascular-related hospitalization over 1 year. We calculated the crude rate of hospitalizations for comparison with trial data. We also calculated the program's potential dollar savings from averting hospitalizations. The average risk of hospitalization in the systematic review's trials was 45%; our population's average observed risk was 18% and the risk among the highest risk patients was 33%. After accounting for the assumed annual intervention cost of $700, the base-case analysis (at $6000 per hospitalization) shows a savings of $122/patient at highest risk; failing to intervene according to predicted risk (no targeting) would actually cost $211/patient. Our findings illustrate how clinical trial findings can be efficiently integrated into community settings by using a prognostic risk score to focus attention on high-risk subgroups.

  1. Risk stratification in the patient with non ST segment elevation acute coronary syndrome.

    PubMed

    Escabí-Mendoza, José; Rosales-Alvarez, Claudia

    2005-12-01

    Patients hospitalized with unstable angina (UA) or with a non-ST segment elevation myocardial infarct (NSTEMI) are at increased risk of suffering refractory angina, recurrent myocardial infarct (MI), and death. These patients need to be evaluated more aggressively. According to the last published guidelines (2002) of UA/NSTEMI by the ACC/AHA Task Force, these patients should be categorized in a risk scale as: low, intermediate or high. This should be done in the initial evaluation, which includes: medical history, physical exam, an electrocardiogram (ECG) and cardiac markers. The TIMI risk score should also be used as complementary in this risk assessment. High risk patients, without contraindications, should be managed more aggressively with coronary angiography. On the other end, low risk patients, and some intermediate, may be evaluated more conservatively with early non-invasive studies for further assessment of ischemia and prognosis.

  2. Risk Stratification for Proven Acute Pulmonary Embolism: What Information Is Needed?

    PubMed

    Barrios, Deisy; Yusen, Roger D; Jiménez, David

    2017-02-01

    Classification of risk drives treatment decisions for patients with acute symptomatic pulmonary embolism (PE). High-risk patients with acute symptomatic PE have hemodynamic instability (i.e., shock or hypotension present), and treatment guidelines suggest systemically administered thrombolytic therapy in this setting. Normotensive PE patients at low risk for early complications (low-risk PE) might benefit from treatment at home or early discharge, while normotensive patients with preserved systemic arterial pressure deemed as having a high risk for PE-related adverse clinical events (intermediate-high-risk PE) might benefit from close observation and consideration of escalation of therapy. Prognostic tools (e.g., clinical prognostic scoring systems, imaging testing, and cardiac laboratory biomarkers) assist with the classification of patients into these categories.

  3. Decreased ADAMTS-13 level is related to inflammation factors and risk stratification of acute lymphoblastic leukemia patients

    PubMed Central

    Liu, Chen; Zhao, Lei; Zhao, Jingzhong; Xu, Qinzhu; Song, Ying; Wang, Hui

    2017-01-01

    Abstract As a kind of metalloprotease of the ADAMTS family, ADAMTS-13 is crucial for maintaining the normal size of von Willebrand factor. Reduced ADAMTS-13 had been reported in patients with both localized and disseminated malignancies. However, the expression and potential role of ADAMTS-13 in hematological malignancies remain unclear. In this research, we measured and compared ADAMTS-13 levels in plasma of 35 acute lymphoblastic leukemia (ALL) patients and 30 healthy controls and found that ALL patients possessed lower level of ADAMTS-13 than controls. Correlations between ADAMTS-13 and inflammation factors were calculated and ADAMTS-13 was negatively correlated with C-reactive protein and interleukin-1β. ALL patients with infections had lower level of ADAMTS-13 than patients without infections. In addition, high-risk ALL patients possessed lower ADAMTS-13 than patients at low risk. To conclude, ADAMTS-13 level is decreased in the plasma of ALL patients and the level of ADAMTS-13 is related to plasma inflammation factors and risk stratification of ALL patients, which could contribute to better understanding of the clinical significance of ADAMTS-13. PMID:28207543

  4. 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.

  5. Integration of Different Risk Assessment Tools to Improve Stratification of Patients with Coronary Artery Disease.

    PubMed

    Paredes, S; Rocha, T; de Carvalho, P; Henriques, J; Morais, J; Ferreira, J

    2015-10-01

    Cardiovascular disease (CVD) causes unaffordable social and health costs that tend to increase as the European population ages. In this context, clinical guidelines recommend the use of risk scores to predict the risk of a cardiovascular disease event. Some useful tools have been developed to predict the risk of occurrence of a cardiovascular disease event (e.g. hospitalization or death). However, these tools present some drawbacks. These problems are addressed through two methodologies: (i) combination of risk assessment tools: fusion of naïve Bayes classifiers complemented with a genetic optimization algorithm and (ii) personalization of risk assessment: subtractive clustering applied to a reduced-dimensional space to create groups of patients. Validation was performed based on two ACS-NSTEMI patient data sets. This work improved the performance in relation to current risk assessment tools, achieving maximum values of sensitivity, specificity, and geometric mean of, respectively, 79.8, 83.8, and 80.9 %. Additionally, it assured clinical interpretability, ability to incorporate of new risk factors, higher capability to deal with missing risk factors and avoiding the selection of a standard CVD risk assessment tool to be applied in the clinical practice.

  6. 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

  7. 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.

  8. A risk stratification algorithm using non-invasive respiratory volume monitoring to improve safety when using post-operative opioids in the PACU.

    PubMed

    Voscopoulos, Christopher; Theos, Kimberly; Tillmann Hein, H A; George, Edward

    2017-04-01

    Late detection of respiratory depression in non-intubated patients compromises patient safety. SpO2 is a lagging indicator of respiratory depression and EtCO2 has proven to be unreliable in non-intubated patients. A decline in minute ventilation (MV) is the earliest sign of respiratory depression. A non-invasive respiratory volume monitor (RVM) that provides accurate, continuous MV measurements enables clinicians to predict and quantify respiratory compromise. For this observational study, practitioners were blinded to the RVM measurements and pain management followed the usual routine. Patients were stratified by their MV on PACU admission and classified as "At-Risk" or "Not-At-Risk," with progression to "Low MV" status following opioids assessed for each category. The purpose was to determine if stratifying based on MV on PACU arrival could identify patients at higher risk for respiratory depression. Ability to identify in advance patients at higher risk for respiratory depression following standard opioid dosing would drive changes in pain management and improve patient care. RVM and opioid administration data from 150 PACU patients following elective joint-replacement surgery were collected in an observational study. "Predicted" MV (MVPRED) and "Percent Predicted" (MVMEASURED/MVPRED × 100 %) were calculated for each patient using standard formulas. Prior to opioid administration, patients were classified as either "Not-At-Risk" (MV ≥ 80 % MVPRED) or "At-Risk" (MV < 80 % MVPRED). "Low MV" was defined as MV < 40 % MVPRED. Post-operative apnea (POA) was defined as ≥5 ten-second apneas per hour of PACU stay. We compared the incidences of Low MV following a single opioid dose, POA, and Low MV at discharge for both groups. In the PACU, 74/150 patients received opioids. Within 15 min of opioid administration, 32 % (24/74) developed Low MV. The risk-stratification algorithm identified 22/24 patients (92 % sensitivity). Only 46 % of them had POA

  9. 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

  10. Effect of Preoperative Risk Group Stratification on Oncologic Outcomes of Patients with Adverse Pathologic Findings at Radical Prostatectomy

    PubMed Central

    Jang, Won Sik; Kim, Lawrence H. C.; Yoon, Cheol Yong; Rha, Koon Ho; Choi, Young Deuk; Hong, Sung Joon; Ham, Won Sik

    2016-01-01

    Background Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy based only on adverse pathologic findings (APFs), irrespective of preoperative risk group. We assessed whether a model incorporating both the preoperative risk group and APFs could predict long-term oncologic outcomes better than a model based on APFs alone. Methods We retrospectively reviewed 4,404 men who underwent radical prostatectomy (RP) at our institution between 1992 and 2014. After excluding patients receiving neoadjuvant therapy or with incomplete pathological or follow-up data, 3,092 men were included in the final analysis. APFs were defined as extraprostatic extension (EPE), seminal vesicle invasion (SVI), or a positive surgical margin (PSM). The adequacy of model fit to the data was compared using the likelihood-ratio test between the models with and without risk groups, and model discrimination was compared with the concordance index (c-index) for predicting biochemical recurrence (BCR) and prostate cancer-specific mortality (PCSM). We performed multivariate Cox proportional hazard model and competing risk regression analyses to identify predictors of BCR and PCSM in the total patient group and each of the risk groups. Results Adding risk groups to the model containing only APFs significantly improved the fit to the data (likelihood-ratio test, p <0.001) and the c-index increased from 0.693 to 0.732 for BCR and from 0.707 to 0.747 for PCSM. A RP Gleason score (GS) ≥8 and a PSM were independently associated with BCR in the total patient group and also each risk group. However, only a GS ≥8 and SVI were associated with PCSM in the total patient group (GS ≥8: hazard ratio [HR] 5.39 and SVI: HR 3.36) and the high-risk group (GS ≥8: HR 6.31 and SVI: HR 4.05). Conclusion The postoperative estimation of oncologic outcomes in men with APFs at RP was improved by considering preoperative risk group stratification. Although a PSM was an

  11. HO-1, RET and PML as possible markers for risk stratification of acute myelocytic leukemia and prognostic evaluation.

    PubMed

    Yu, Meisheng; Wang, Jishi; Ma, Dan; Chen, Shuya; Lin, Xiaojing; Fang, Qin; Zhe, Nana

    2015-11-01

    Heme oxygenase-1 (HO-1) is an inducible isoform of HO that is activated in response to oxidative stress and has anti-apoptotic and pro-proliferative effects on leukemia cells. RET, a tyrosine kinase receptor; its expression levels are associated with the differentiation degree of acute myelocytic leukemia (AML) cells. The promyelocytic leukemia (PML) gene inhibits cell proliferation and tumor growth, participates in the differentiation of hematopoietic progenitor cells and induces cell apoptosis. However, the association between the expression levels of HO-1, RET and PML genes and the risk stratification of AML and prognosis have not previously been reported. In the present study, HO-1 was expressed in the human AML Kasumi-1, HL-60 and THP-1 cell lines, and HO-1 expression was regulated by Hemin (20 µmol/l) and ZnPPIX (10 µmol/l). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that expression of RET and PML were positively and negatively correlated with HO-1 expression, respectively. Bone marrow samples (18 favorable, 55 intermediate, 15 adverse and 2 unknown karyotype AML cases and 20 healthy donors) were collected from 90 randomly selected AML patients upon their first visit. The mRNA and protein expression of HO-1, RET and PML in samples was detected by RT-qPCR and western blot analysis. At the mRNA level, the adverse group expressed significantly higher levels of HO-1 and RET compared with the levels in the favorable and normal groups. The PML mRNA expression levels in adverse patient samples was lower compared with those of the intermediate group and favorable group. Western blot analysis demonstrated that the expression levels of HO-1, RET and PML proteins in all risk groups exhibited the same pattern of expression as was observed for the mRNA levels. The overall survival and relapse-free survival rates were shortest in AML patients with high HO-1 expression (Kaplan-Meier; log-rank, P<0.01). The results of the

  12. An electrophysiologist perspective on risk stratification in heart failure: can better understanding of the condition of the cardiac sympathetic nervous system help?

    PubMed

    Borgquist, Rasmus; Singh, Jagmeet P

    2015-06-01

    Heart failure is often complicated by arrhythmias that can adversely affect the quality of life and increase the risk for sudden cardiac death. Current risk stratification strategies for sudden cardiac death in the heart failure patient are not ideal, with much potential for further refinement. Overactivation of the sympathetic nervous system has been shown to be associated with worsening heart failure as well as arrhythmic events. Recent advances in our understanding of the autonomic nervous system and new methods for quantification of the pathologic activation of the sympathetic nerves have triggered increasing interest in this field. This viewpoint focuses on the need for and challenges of risk stratification of sudden death in the heart failure patient and discusses the potential value of measuring sympathetic nervous system activity to better stratify risk and to select patients with heart failure for implantable cardioverter defibrillator therapy.

  13. Monoclonal gammopathy of undetermined significance: Using risk stratification to guide follow-up.

    PubMed

    Uddin, Zia; Maennle, Diane; Russell, Kimberly; Boltri, John M

    2015-07-01

    Varying combinations of 3 measurable factors determine a patient's risk of progressing toward multiple myeloma and influence monitoring decisions. This review--and accompanying algorithm--can guide your approach. For monoclonal gammopathy of undetermined significance (MGUS) patients at low risk, repeat serum protein electrophoresis (SPE) in 6 months. If no significant elevation of M-protein is found, repeat SPE every 2 to 3 years.

  14. Development of a Bayesian Classifier for Breast Cancer Risk Stratification: A Feasibility Study

    DTIC Science & Technology

    2010-03-29

    women, and raloxifene may be considered in postmenopausal women, with lobular carcinoma in situ or with a 5-year breast cancer risk estimate of 1.66% or...Multiple Outcomes of Raloxifene Evaluation (MORE), Continuing Outcomes Relevant to Evista (CORE), Raloxifene Use for the Heart (RUTH,) and NSABP Study of...Tamoxifen and Raloxifene (STAR) trials demonstrated consistent significant reductions in estrogen receptor-positive breast cancer incidence in at-risk

  15. Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

    PubMed Central

    García-Fernández, Amaya; Roldán, Vanessa; Rivera-Caravaca, José Miguel; Hernández-Romero, Diana; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y. H.; Marín, Francisco

    2017-01-01

    Von Willebrand factor (vWF) is a biomarker of endothelial dysfunction. We investigated its role on prognosis in anticoagulated atrial fibrillation (AF) patients and determined whether its addition to clinical risk stratification schemes improved event-risk prediction. Consecutive outpatients with non-valvular AF were recruited and rates of thrombotic/cardiovascular events, major bleeding and mortality were recorded. The effect of vWF on prognosis was calculated using a Cox regression model. Improvements in predictive accuracy over current scores were determined by calculating the integrated discrimination improvement (IDI), net reclassification improvement (NRI), comparison of receiver-operator characteristic (ROC) curves and Decision Curve Analysis (DCA). 1215 patients (49% males, age 76 (71–81) years) were included. Follow-up was almost 7 years. Significant associations were found between vWF and cardiovascular events, stroke, mortality and bleeding. Based on IDI and NRI, addition of vWF to CHA2DS2-VASc statistically improved its predictive value, but c-indexes were not significantly different. For major bleeding, the addition of vWF to HAS-BLED improved the c-index but not IDI or NRI. DCA showed minimal net benefit. vWF acts as a simple prognostic biomarker in AF and, whilst its addition to current scores statistically improves prediction for some endpoints, absolute changes and impact on clinical decision-making are marginal. PMID:28134282

  16. 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.

  17. 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

  18. Risk stratification of patients with non-ST-elevation acute coronary syndromes by assessing global longitudinal strain.

    PubMed

    Hoshi, Hiromi; Takagi, Atsushi; Uematsu, Shoko; Ashihara, Kyomi; Hagiwara, Nobuhisa

    2014-05-01

    Noninvasive detection of left main/three-vessel diseases (LM/3VD) among patients with non-ST-elevation acute coronary syndromes (NSTEACS) has been difficult using echocardiography. However, two-dimensional (2D) strain/strain-rate analysis is more sensitive in quantitatively assessing contractile abnormality. Accordingly, we aimed to clarify the usefulness of 2D strain/strain-rate analysis for risk stratification of NSTEACS. A total of 50 patients with NSTEACS underwent echocardiography and coronary angiography. We evaluated global longitudinal peak strain (global PS), peak systolic strain rate (global SSR), early diastolic global peak strain rate (global ESR), time from aortic valve closure to peak strain (TAVC-global PS), and global ESR (TAVC-global ESR) in apical four-, two-, and three-chamber views. Patients were divided into two groups according to coronary angiographic findings, the high-risk group (n = 15) with either of left main or three-vessel disease, and the low-risk group (n = 35). There were no significant differences in global SSR and global ESR between the two groups. The amplitude of global PS was significantly reduced in high-risk patients with LM/3VD in comparison with low-risk patients (-17.5 ± 2.4% vs -19.8 ± 2.7%, P = 0.007, respectively). TAVC-global PS and TAVC-global ESR were significantly prolonged in high-risk patients with LM/3VD in comparison with low-risk patients (15.3 ± 25.7 ms vs -36.8 ± 32.7 ms, P < 0.0001 and 162.8 ± 32.7 ms vs 135.7 ± 41.5 ms, P < 0.03, respectively). Receiver-operating characteristic analysis demonstrated that TAVC-global PS most strongly detected high-risk patients with sensitivity of 100% and specificity of 74.3% (area under the curve = 0.938, 95 % confidence interval 0.832-0.986, P = 0.0001). Temporal analysis of 2D strain appeared to be useful in detecting high-risk patients with LM/3VD among patients with NSTEACS.

  19. 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

  20. Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features

    PubMed Central

    Palomo, Laura; Garcia, Olga; Arnan, Montse; Xicoy, Blanca; Fuster, Francisco; Cabezón, Marta; Coll, Rosa; Ademà, Vera; Grau, Javier; Jiménez, Maria-José; Pomares, Helena; Marcé, Sílvia; Mallo, Mar; Millá, Fuensanta; Alonso, Esther; Sureda, Anna; Gallardo, David; Feliu, Evarist; Ribera, Josep-Maria; Solé, Francesc; Zamora, Lurdes

    2016-01-01

    Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC. PMID:27486981

  1. 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

  2. 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

  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. Call for Standardized Definitions of Osteoarthritis and Risk Stratification for Clinical Trials and Clinical Use

    PubMed Central

    Kraus, Virginia Byers; Blanco, Francisco J.; Englund, Martin; Karsdal, Morten A.; Lohmander, L. Stefan

    2015-01-01

    Osteoarthritis is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for osteoarthritis (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 Osteoarthritis Development) and ROAP (Risk of Osteoarthritis 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

  5. Brugada syndrome and fitness to fly: risk stratification in two pilot applicants.

    PubMed

    Dobler, Diana; Huber, Samuel W; Maire, René

    2010-08-01

    Brugada syndrome is a condition associated with a characteristic ECG and sudden arrhythmic death. Due to this risk of sudden death, patients with Brugada syndrome are generally not considered fit to fly. In recent years we have gained new insight into this condition and Brugada syndrome patients can now be classified into different risk categories. This then raises the question of whether a subset of patients with the Brugada syndrome exists in whom the risk of sudden death is sufficiently low and is compatible with fitness to fly. We discuss this question with two case reports of persons with Brugada syndrome who applied for an airman medical certificate and we propose an algorithm to aid decision making in this situation.

  6. 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.

  7. A genetic approach to stratification of risk for age-related macular degeneration.

    PubMed

    Zanke, Brent; Hawken, Steven; Carter, Ronald; Chow, David

    2010-02-01

    The genetic determinants of age-related macular degeneration (AMD) are reviewed and a novel approach to risk determination based upon inherited genetic polymorphisms and smoking history is presented. Although AMD was long thought to have primarily an environmental etiology, genetic variation is now known to account for the majority of the disease risk, with variations in the genes of the complement pathways playing a prominent role. Independent and validated clinical studies have implicated the C3 gene and its regulator, complement factor H (1q31.1), complement component 2 (6q21.33), and complement factor B (6q21.33). Subtle variations in complement activity increase the risk of symptomatic macular inflammation with age. A second group of AMD-associated genetic markers may aggravate complement-mediated inflammation by permitting retinal oxidative damage. Variation within the chromosomal site (10q26) coding a mitochondrial-associated protein (age-related maculopathy susceptibility 2) and an independent variation within the mitochondrial genome itself (A4917G) suggest a contributing pathophysiological role of retinal oxidative stress. A genetic panel of disease-susceptibility markers and smoking history can identify a group of individuals with greater than 65% lifetime risk of AMD. The introduction of genetic marker testing into clinical practice may identify patients with early disease who may be aided by presymptomatic monitoring or inclusion into trials of newer prophylactic agents.

  8. Computational cardiology and risk stratification for sudden cardiac death: one of the grand challenges for cardiology in the 21st century.

    PubMed

    Hill, Adam P; Perry, Matthew D; Abi-Gerges, Najah; Couderc, Jean-Philippe; Fermini, Bernard; Hancox, Jules C; Knollmann, Bjorn C; Mirams, Gary R; Skinner, Jon; Zareba, Wojciech; Vandenberg, Jamie I

    2016-12-01

    Risk stratification in the context of sudden cardiac death has been acknowledged as one of the major challenges facing cardiology for the past four decades. In recent years, the advent of high performance computing has facilitated organ-level simulation of the heart, meaning we can now examine the causes, mechanisms and impact of cardiac dysfunction in silico. As a result, computational cardiology, largely driven by the Physiome project, now stands at the threshold of clinical utility in regards to risk stratification and treatment of patients at risk of sudden cardiac death. In this white paper, we outline a roadmap of what needs to be done to make this translational step, using the relatively well-developed case of acquired or drug-induced long QT syndrome as an exemplar case.

  9. Computational cardiology and risk stratification for sudden cardiac death: one of the grand challenges for cardiology in the 21st century

    PubMed Central

    Perry, Matthew D.; Abi‐Gerges, Najah; Couderc, Jean‐Philippe; Fermini, Bernard; Hancox, Jules C.; Knollmann, Bjorn C.; Mirams, Gary R.; Skinner, Jon; Zareba, Wojciech; Vandenberg, Jamie I.

    2016-01-01

    Abstract Risk stratification in the context of sudden cardiac death has been acknowledged as one of the major challenges facing cardiology for the past four decades. In recent years, the advent of high performance computing has facilitated organ‐level simulation of the heart, meaning we can now examine the causes, mechanisms and impact of cardiac dysfunction in silico. As a result, computational cardiology, largely driven by the Physiome project, now stands at the threshold of clinical utility in regards to risk stratification and treatment of patients at risk of sudden cardiac death. In this white paper, we outline a roadmap of what needs to be done to make this translational step, using the relatively well‐developed case of acquired or drug‐induced long QT syndrome as an exemplar case. PMID:27060987

  10. 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.

  11. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations.

    PubMed

    Pagano, Livio; Busca, Alessandro; Candoni, Anna; Cattaneo, Chiara; Cesaro, Simone; Fanci, Rosa; Nadali, Gianpaolo; Potenza, Leonardo; Russo, Domenico; Tumbarello, Mario; Nosari, Annamaria; Aversa, Franco

    2017-03-01

    Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. The extensive use of antifungal prophylaxis has reduced the infections from yeasts (e.g., candidemia) even though they are still associated with high mortality rates. This paper analyzes concurrent multiple predisposing factors that could favor the onset of fungal infections. Although neutropenia is common to almost all hematologic patients, other factors play a key role in specific patients, in particular in patients with AML or allogeneic HSCT recipients. Defining those patients at higher risk of IFIs may help to design the most appropriate diagnostic work-up and antifungal strategy.

  12. Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

    PubMed Central

    Oran, Betül; Jorgensen, Jeff L.; Marin, David; Wang, Sa; Ahmed, Sairah; Alousi, Amin M.; Andersson, Borje S.; Bashir, Qaiser; Bassett, Roland; Lyons, Genevieve; Chen, Julianne; Rezvani, Katy; Popat, Uday; Kebriaei, Partow; Patel, Keyur; Rondon, Gabriela; Shpall, Elizabeth J.; Champlin, Richard E.

    2017-01-01

    Our aim was to improve outcome prediction after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia by combining cytogenetic and molecular data at diagnosis with minimal residual disease assessment by multicolor flow-cytometry at transplantation. Patients with acute myeloid leukemia in first complete remission in whom minimal residual disease was assessed at transplantation were included and categorized according to the European LeukemiaNet classification. The primary outcome was 1-year relapse incidence after transplantation. Of 152 patients eligible, 48 had minimal residual disease at the time of their transplant. Minimal residual disease-positive patients were older, required more therapy to achieve first remission, were more likely to have incomplete recovery of blood counts and had more adverse risk features by cytogenetics. Relapse incidence at 1 year was higher in patients with minimal residual disease (32.6% versus 14.4%, P=0.002). Leukemia-free survival (43.6% versus 64%, P=0.007) and overall survival (48.8% versus 66.9%, P=0.008) rates were also inferior in patients with minimal residual disease. In multivariable analysis, minimal residual disease status at transplantation independently predicted 1-year relapse incidence, identifying a subgroup of intermediate-risk patients, according to the European LeukemiaNet classification, with a particularly poor outcome. Assessment of minimal residual disease at transplantation in combination with cytogenetic and molecular findings provides powerful independent prognostic information in acute myeloid leukemia, lending support to the incorporation of minimal residual disease detection to refine risk stratification and develop a more individualized approach during hematopoietic stem cell transplantation. PMID:27540139

  13. Artificial Neural Networks and risk stratification models in Emergency Departments: The policy maker's perspective.

    PubMed

    Casagranda, Ivo; Costantino, Giorgio; Falavigna, Greta; Furlan, Raffaello; Ippoliti, Roberto

    2016-01-01

    The primary goal of Emergency Department (ED) physicians is to discriminate between individuals at low risk, who can be safely discharged, and patients at high risk, who require prompt hospitalization. The problem of correctly classifying patients is an issue involving not only clinical but also managerial aspects, since reducing the rate of admission of patients to EDs could dramatically cut costs. Nevertheless, a trade-off might arise due to the need to find a balance between economic interests and the health conditions of patients. This work considers patients in EDs after a syncope event and presents a comparative analysis between two models: a multivariate logistic regression model, as proposed by the scientific community to stratify the expected risk of severe outcomes in the short and long run, and Artificial Neural Networks (ANNs), an innovative model. The analysis highlights differences in correct classification of severe outcomes at 10 days (98.30% vs. 94.07%) and 1 year (97.67% vs. 96.40%), pointing to the superiority of Neural Networks. According to the results, there is also a significant superiority of ANNs in terms of false negatives both at 10 days (3.70% vs. 5.93%) and at 1 year (2.33% vs. 10.07%). However, considering the false positives, the adoption of ANNs would cause an increase in hospital costs, highlighting the potential trade-off which policy makers might face.

  14. Usefulness of Neutrophil-to-Lymphocyte Ratio in Risk Stratification of Patients with Advanced Heart Failure

    PubMed Central

    Benites-Zapata, Vicente A.; Hernandez, Adrian V.; Nagarajan, Vijaiganesh; Cauthen, Clay A.; Starling, Randall C.; Tang, W. H. Wilson

    2014-01-01

    Elevated neutrophil-to-lymphocyte Ratio (NLR) has been associated with increased mortality in patients with acute heart failure (HF) as well as in neoplastic diseases. We investigated the association between NLR and mortality or cardiac transplantation in a retrospective cohort of 527 patients presented to the Cleveland Clinic for evaluation of advanced HF therapy options between 2007 and 2010. Patients were divided according to low, intermediate, and high tertiles of NLR, and were followed longitudinally for time to all-causes mortality or heart transplantation (primary outcome). The median NLR was 3.9 (IQR 2.5, 6.5). In univariate analysis, intermediate and highest tertiles of NLR had a higher risk than the lowest tertile for the primary outcome and all-causes mortality. Compared to the lowest tertile, there was no difference in the risk of heart transplantation for intermediate and high tertiles. In multivariate analysis, when compared to the lowest tertile, the intermediate and high NLR tertiles remained significantly associated with the primary outcome (HR=1.61 [95%CI 1.10 to 2.37] and HR=1.55 [95%CI 1.02 to 2.36], respectively), and all-causes mortality (HR=1.83 [95%CI 1.07 to 3.14] and HR=2.16 [95%CI 1.21 to 3.83], respectively). In conclusion, elevated NLR is associated with increased mortality or heart transplantation risk in patients with advanced HF. PMID:25456873

  15. Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure.

    PubMed

    Benites-Zapata, Vicente A; Hernandez, Adrian V; Nagarajan, Vijaiganesh; Cauthen, Clay A; Starling, Randall C; Tang, W H Wilson

    2015-01-01

    Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in patients with acute heart failure (HF) and neoplastic diseases. We investigated the association between NLR and mortality or cardiac transplantation in a retrospective cohort of 527 patients presented to the Cleveland Clinic for evaluation of advanced HF therapy options from 2007 to 2010. Patients were divided according to low, intermediate, and high tertiles of NLR and were followed longitudinally for time to all-cause mortality or heart transplantation (primary outcome). The median NLR was 3.9 (interquartile range 2.5 to 6.5). In univariate analysis, intermediate and highest tertiles of NLR had a higher risk than the lowest tertile for the primary outcome and all-causes mortality. Compared with the lowest tertile, there was no difference in the risk of heart transplantation for intermediate and high tertiles. In multivariate analysis, compared with the lowest tertile, the intermediate and high NLR tertiles remained significantly associated with the primary outcome (hazard ratio [HR] = 1.61, 95% confidence interval [CI] 1.10 to 2.37 and HR = 1.55, 95% CI 1.02 to 2.36, respectively) and all-cause mortality (HR = 1.83, 95% CI 1.07 to 3.14 and HR = 2.16, 95% CI 1.21 to 3.83, respectively). In conclusion, elevated NLR is associated with increased mortality or heart transplantation risk in patients with advanced HF.

  16. 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.

  17. A comparison of non-symmetric entropy-based classification trees and support vector machine for cardiovascular risk stratification.

    PubMed

    Singh, Anima; Guttag, John V

    2011-01-01

    Classification tree-based risk stratification models generate easily interpretable classification rules. This feature makes classification tree-based models appealing for use in a clinical setting, provided that they have comparable accuracy to other methods. In this paper, we present and evaluate the performance of a non-symmetric entropy-based classification tree algorithm. The algorithm is designed to accommodate class imbalance found in many medical datasets. We evaluate the performance of this algorithm, and compare it to that of SVM-based classifiers, when applied to 4219 non-ST elevation acute coronary syndrome patients. We generated SVM-based classifiers using three different strategies for handling class imbalance: cost-sensitive SVM learning, synthetic minority oversampling (SMOTE), and random majority undersampling. We used both linear and radial basis kernel-based SVMs. Our classification tree models outperformed SVM-based classifiers generated using each of the three techniques. On average, the classification tree models yielded a 14% improvement in G-score and a 21% improvement in F-score relative to the linear SVM classifiers with the best performance. Similarly, our classification tree models yielded a 12% improvement in G-score and a 21% improvement in the F-score over the best RBF kernel-based SVM classifiers.

  18. Risk stratification in multiple myeloma, part 2: the significance of genetic risk factors in the era of currently available therapies.

    PubMed

    Biran, Noa; Jagannath, Sundar; Chari, Ajai

    2013-01-01

    Multiple myeloma (MM) is a heterogeneous disease, and a variety of risk factors at the time of initial diagnosis can be used to stratify patients. In the first part of this 2-part series, we reviewed the currently identified prognostic factors, characterized by disease burden, host factors, tumor biology, and depth of response to therapy. However, these risk factors cannot be interpreted independently of therapies. Novel therapies have the potential to worsen or improve outcomes compared with conventional therapy in high-risk patients, or actually overcome the high-risk status, thereby resulting in reclassification as standard risk. For example, thalidomide (Thalomid, Celgene) is associated with worse outcomes in patients with high-risk cytogenetic abnormalities, such as deletion of chromosomes 13 and 17p, whereas proteasome inhibitors appear to overcome t(4;14). The second part of this series reviews the significance of various genetic risks in the era of novel therapies for MM.

  19. 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

  20. Risk stratification in the hormonal treatment of patients with prostate cancer.

    PubMed

    Uhlman, Matthew A; Moul, Judd W; Tang, Ping; Stackhouse, Danielle A; Sun, Leon

    2009-09-01

    Prostate cancer (PCa) is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be 186,320 new cases of prostate cancer in the United States in 2008. About 28,660 men will die of this disease this year and PCa remains the second-leading cause of cancer death in men. One in six men will get PCa during his lifetime and one in 35 will die of the disease. Today, more than 2 million men in the United States who have had PCa are still alive. The death rate for PCa continues to decline, chiefly due to early detection and treatment, and improved salvage therapy such as hormone therapy (HT). HT continues to be a mainstay for primary-recurrent PCa and locally-advanced PCa. However, HT is associated with many undesirable side effects including sexual dysfunction, osteoporosis and hot flashes, all of which can lead to decreased quality of life (QOL). These risks are seen in both long- and short-term HT regimens. Additionally, research in recent years has revealed trends related to clinico pathological variables and their predictive ability in HT outcomes. Awareness of the potential adverse effects, the risks associated with HT and the prognostic ability of clinical and pathological variables is important in determining optimal therapy for individual patients. A rigorous evaluation of the current scientific literature associated with HT was conducted with the goal of identifying the most favorable balance of benefits and risks associated with HT.

  1. Accurate numerical simulation of the far-field tsunami caused by the 2011 Tohoku earthquake, including the effects of Boussinesq dispersion, seawater density stratification, elastic loading, and gravitational potential change

    NASA Astrophysics Data System (ADS)

    Baba, Toshitaka; Allgeyer, Sebastien; Hossen, Jakir; Cummins, Phil R.; Tsushima, Hiroaki; Imai, Kentaro; Yamashita, Kei; Kato, Toshihiro

    2017-03-01

    In this study, we considered the accurate calculation of far-field tsunami waveforms by using the shallow water equations and accounting for the effects of Boussinesq dispersion, seawater density stratification, elastic loading, and gravitational potential change in a finite difference scheme. By comparing numerical simulations that included and excluded each of these effects with the observed waveforms of the 2011 Tohoku tsunami, we found that all of these effects are significant and resolvable in the far field by the current generation of deep ocean-bottom pressure gauges. Our calculations using previously published, high-resolution models of the 2011 Tohoku tsunami source exhibited excellent agreement with the observed waveforms to a degree that has previously been possible only with near-field or regional observations. We suggest that the ability to model far-field tsunamis with high accuracy has important implications for tsunami source and hazard studies.

  2. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management

    PubMed Central

    Wilcox, Ryan A.

    2015-01-01

    Disease overview Cutaneous T-cell lymphomas are a heterogenous group of T-cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Diagnosis The diagnosis of MF or SS requires the integration of clinical and histopathologic data. Risk-adapted therapy TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk-adapted,” multi-disciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or blood involvement are generally approached with biologic-response modifiers or histone deacetylase inhibitors prior to escalating therapy to include systemic, single-agent chemotherapy. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients. PMID:26607183

  3. Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature.

    PubMed

    Tomioka, N; Oba, S; Ohira, M; Misra, A; Fridlyand, J; Ishii, S; Nakamura, Y; Isogai, E; Hirata, T; Yoshida, Y; Todo, S; Kaneko, Y; Albertson, D G; Pinkel, D; Feuerstein, B G; Nakagawara, A

    2008-01-17

    Human neuroblastoma remains enigmatic because it often shows spontaneous regression and aggressive growth. The prognosis of advanced stage of sporadic neuroblastomas is still poor. Here, we investigated whether genomic and molecular signatures could categorize new therapeutic risk groups in primary neuroblastomas. We conducted microarray-based comparative genomic hybridization (array-CGH) with a DNA chip carrying 2464 BAC clones to examine genomic aberrations of 236 neuroblastomas and used in-house cDNA microarrays for gene-expression profiling. Array-CGH demonstrated three major genomic groups of chromosomal aberrations: silent (GGS), partial gains and/or losses (GGP) and whole gains and/or losses (GGW), which well corresponded with the patterns of chromosome 17 abnormalities. They were further classified into subgroups with different outcomes. In 112 sporadic neuroblastomas, MYCN amplification was frequent in GGS (22%) and GGP (53%) and caused serious outcomes in patients. Sporadic tumors with a single copy of MYCN showed the 5-year cumulative survival rates of 89% in GGS, 53% in GGP and 85% in GGW. Molecular signatures also segregated patients into the favorable and unfavorable prognosis groups (P=0.001). Both univariate and multivariate analyses revealed that genomic and molecular signatures were mutually independent, powerful prognostic indicators. Thus, combined genomic and molecular signatures may categorize novel risk groups and confer new clues for allowing tailored or even individualized medicine to patients with neuroblastoma.

  4. Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies.

    PubMed

    Pryma, Daniel A; Mandel, Susan J

    2014-09-01

    Differentiated thyroid cancers are typically iodine-avid and can be effectively treated with radioiodine. In most patients, radioiodine treatment is done for ablation of residual tissue, and in these cases the focus should be on using the minimum effective dose. Adjuvant therapy can be done to reduce the risk of recurrence, but optimal patient selection and dose are unclear. Patients with advanced disease benefit most from treatment with the maximum-tolerated dose. Recent research has focused on better patient selection and reduced radioiodine doses for remnant ablation. There are emerging targeted therapeutic approaches in patients who are appropriately shown to have iodine-refractory disease, with 1 drug approved by the Food and Drug Administration. Numerous trials are ongoing to assess targeted therapeutics alone or in combination with radioiodine.

  5. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.

    PubMed

    Morita, Hiroshi; Zipes, Douglas P; Wu, Jiashin

    2009-11-01

    Brugada syndrome (BrS), caused by ion channel abnormalities, is characterized by ST segment elevation and negative T waves in the right precordial electrocardiographic (ECG) leads recorded over the right ventricular outflow tract (RVOT). BrS is sensitive to body temperature and can lead to T-wave alternans (TWA), ventricular tachycardia, and sudden death. Recent studies in an isolated canine RVOT model of BrS demonstrated that reversal of the transmural gradient of repolarization caused the ECG characteristics and that major intraepicardial and transmural dispersion of action potentials (APs) initiated phase 2 reentry, premature ventricular activations, and tachyarrhythmias. Hypothermia enhanced the heterogeneity of the AP and promoted the origination of phase 2 reentry in the epicardium of the RVOT, but the prolonged AP duration frequently blocked reentry. Hyperthermia abbreviated the AP and facilitated the maintenance of reentry and tachyarrhythmias. Bradycardia promoted alternans in the phase 2 dome of the AP within the epicardium of the RVOT, resulting in TWA. The above phenomena were localized in the epicardium of the RVOT. Blockade of the transient outward current, I(to), reduced AP heterogeneity and prevented arrhythmias in the BrS model. In addition, epicardial activation delay led to fragmented QRS, a risk marker of prognosis in BrS. Body surface mapping in patients with BrS supported these experimental findings. In conclusion, the AP heterogeneity within the epicardium of the RVOT contributes to the ECG characteristics, temperature sensitivity, TWA, and arrhythmias in BrS, and body surface mapping and fragmented QRS can be effective predictors of risk in patients with BrS.

  6. Validation of a risk stratification tool for fall-related injury in a state-wide cohort

    PubMed Central

    McCoy, Thomas H; Castro, Victor M; Cagan, Andrew; Roberson, Ashlee M; Perlis, Roy H

    2017-01-01

    details. This translatable approach to stratification allows for identification of high-risk individuals in whom interventions are likely to be cost-effective. PMID:28167743

  7. Stage II/III rectal cancer with intermediate response to preoperative radiochemotherapy: Do we have indications for individual risk stratification?

    PubMed Central

    2010-01-01

    Background Response to preoperative radiochemotherapy (RCT) in patients with locally advanced rectal cancer is very heterogeneous. Pathologic complete response (pCR) is accompanied by a favorable outcome. However, most patients show incomplete response. The aim of this investigation was to find indications for risk stratification in the group of intermediate responders to RCT. Methods From a prospective database of 496 patients with rectal adenocarcinoma, 107 patients with stage II/III cancers and intermediate response to preoperative 5-FU based RCT (ypT2/3 and TRG 2/3), treated within the German Rectal Cancer Trials were studied. Surgical treatment comprised curative (R0) total mesorectal excision (TME) in all cases. In 95 patients available for statistical analyses, residual transmural infiltration of the mesorectal compartment, nodal involvement and histolologic tumor grading were investigated for their prognostic impact on disease-free (DFS) and overall survival (OS). Results Residual tumor transgression into the mesorectal compartment (ypT3) did not influence DFS and OS rates (p = 0.619, p = 0.602, respectively). Nodal involvement after preoperative RCT (ypN1/2) turned out to be a valid prognostic factor with decreased DFS and OS (p = 0.0463, p = 0.0236, respectively). Persistent tumor infiltration of the mesorectum (ypT3) and histologic tumor grading of residual tumor cell clusters were strongly correlated with lymph node metastases after neoadjuvant treatment (p < 0.001). Conclusions Advanced transmural tumor invasion after RCT does not affect prognosis when curative (R0) resection is achievable. Residual nodal status is the most important predictor of individual outcome in intermediate responders to preoperative RCT. Furthermore, ypT stage and tumor grading turn out to be additional auxiliary factors. Future clinical trials for risk-adapted adjuvant therapy should be based on a synopsis of clinicopathologic parameters. PMID:20388220

  8. 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.

  9. Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease: Long-Term Cohort Study.

    PubMed

    Minutolo, Roberto; Gabbai, Francis B; Chiodini, Paolo; Garofalo, Carlo; Stanzione, Giovanna; Liberti, Maria Elena; Pacilio, Mario; Borrelli, Silvio; Provenzano, Michele; Conte, Giuseppe; De Nicola, Luca

    2015-09-01

    In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m(2), and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04-1.21 and 1.18, 1.08-1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005-0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29-3.59 and 1.71, 1.07-2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.

  10. 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.

  11. Usefulness of the QRS-T angle to improve long-term risk stratification of patients with acute myocardial infarction and depressed left ventricular ejection fraction.

    PubMed

    Raposeiras-Roubín, Sergio; Virgós-Lamela, Alejandro; Bouzas-Cruz, Noelia; López-López, Andrea; Castiñeira-Busto, María; Fernández-Garda, Rita; García-Castelo, Alberto; Rodríguez-Mañero, Moisés; García-Acuña, José María; Abu-Assi, Emad; González-Juanatey, José Ramón

    2014-04-15

    In light of the low cost, the widespread availability of the electrocardiogram, and the increasing economic burden of the health-related problems, we aimed to analyze the prognostic value of automatic frontal QRS-T angle to predict mortality in patients with left ventricular (LV) systolic dysfunction after acute myocardial infarction (AMI). About 467 consecutive patients discharged with diagnosis of AMI and with LV ejection fraction ≤40% were followed during 3.9 years (2.1 to 5.9). From them, 217 patients (47.5%) died. The frontal QRS-T angle was higher in patients who died (116.6±52.8 vs 77.9±55.1, respectively, p<0.001). The QRS-T angle value of 90° was the most accurate to predict all-cause cardiac death. After multivariate analysis, frontal QRS-T angle remained as an excellent predictor of all-cause and cardiac deaths, increasing the mortality 6% per each 10°. For the global mortality, the hazard ratio for a QRS-T angle>90° was 2.180 (1.558 to 3.050), and for the combined end point of cardiac death and appropriate implantable cardioverter defribrillator therapy, it was 2.385 (1.570 to 3.623). This independent predictive value was maintained even after adjusting by bundle brunch block, ST-elevation AMI, and its localization. In conclusion, a wide automatic frontal QRS-T angle (>90°) is a good discriminator of long-term mortality in patients with LV systolic dysfunction after an AMI. The ability to easily measure it from a standard 12-lead electrocardiogram together with its prognostic value makes the frontal QRS-T angle an attractive tool to help clinicians to improve risk stratification of those patients.

  12. 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

  13. The DecisionDx-UM Gene Expression Profile Test Provides Risk Stratification and Individualized Patient Care in Uveal Melanoma.

    PubMed

    Harbour, J William; Chen, Royce

    2013-04-09

    Uveal melanoma (UM) is the most common primary cancer of the eye and has a strong propensity for metastasis. Although there have been many recent improvements in the diagnosis and treatment of UM, and only 2-4% of patients present with detectable metastasis, up to half of patients are at risk for dying of metastatic disease. Clinicopathologic factors are not accurate enough for individualized patient care. Chromosomal alterations have been used for prognostic purposes, but the routine clinical use of these methods is limited by their susceptibility to sampling error resulting from tumor heterogeneity, limited clinical validation, lack of standardized testing platforms, and high technical failure rates. In contrast, the DecisionDx-UM gene expression profile test is a stand-alone platform which requires no other information for maximal prognostic accuracy and which circumvents many of the drawbacks of chromosomal methods through the use of a highly sensitive microfluidics, PCR-based platform that simultaneously measures the expression of 15 carefully selected genes from primary uveal melanoma samples obtained by fine needle biopsy. Low metastatic risk is reported as Class 1, and high metastatic risk as Class 2. The test allows patients to be stratified into risk categories such that high-risk patients can be offered intensive metastatic surveillance and adjuvant therapy while low-risk patients can be spared these interventions. This test is now used as part of the standard of care in many ocular oncology centers.

  14. Development and Validation of a Stratification Tool for Predicting Risk of Deep Sternal Wound Infection after Coronary Artery Bypass Grafting at a Brazilian Hospital

    PubMed Central

    Sá, Michel Pompeu Barros Oliveira; Ferraz, Paulo Ernando; Soares, Artur Freire; Miranda, Rodrigo Gusmão Albuquerque; Araújo, Mayara Lopes; Silva, Frederico Vasconcelos; Lima, Ricardo de Carvalho

    2017-01-01

    Objective Deep sternal wound infection following coronary artery bypass grafting is a serious complication associated with significant morbidity and mortality. Despite the substantial impact of deep sternal wound infection, there is a lack of specific risk stratification tools to predict this complication after coronary artery bypass grafting. This study was undertaken to develop a specific prognostic scoring system for the development of deep sternal wound infection that could risk-stratify patients undergoing coronary artery bypass grafting and be applied right after the surgical procedure. Methods Between March 2007 and August 2016, continuous, prospective surveillance data on deep sternal wound infection and a set of 27 variables of 1500 patients were collected. Using binary logistic regression analysis, we identified independent predictors of deep sternal wound infection. Initially we developed a predictive model in a subset of 500 patients. Dataset was expanded to other 1000 consecutive cases and a final model and risk score were derived. Calibration of the scores was performed using the Hosmer-Lemeshow test. Results The model had area under Receiver Operating Characteristic (ROC) curve of 0.729 (0.821 for preliminary dataset). Baseline risk score incorporated independent predictors of deep sternal wound infection: obesity (P=0.046; OR 2.58; 95% CI 1.11-6.68), diabetes (P=0.046; OR 2.61; 95% CI 1.12-6.63), smoking (P=0.008; OR 2.10; 95% CI 1.12-4.67), pedicled internal thoracic artery (P=0.012; OR 5.11; 95% CI 1.42-18.40), and on-pump coronary artery bypass grafting (P=0.042; OR 2.20; 95% CI 1.13-5.81). A risk stratification system was, then, developed. Conclusion This tool effectively predicts deep sternal wound infection risk at our center and may help with risk stratification in relation to public reporting and targeted prevention strategies in patients undergoing coronary artery bypass grafting.

  15. Identifying inequities in maternal and child health through risk stratification to inform health systems strengthening in Northern Togo

    PubMed Central

    McCarthy, Katharine J.; Braganza, Sandra; Fiori, Kevin; Gbeleou, Christophe; Kpakpo, Vivien; Lopez, Andrew; Schechter, Jennifer; Singham Goodwin, Alicia; Jones, Heidi E.

    2017-01-01

    Objective In Togo, substantial progress in maternal and child health is needed to reach global development goals. To better inform clinic and community-based health services, this study identifies factors associated with maternal and child health care utilization in the Kara region of Northern Togo. Methods We conducted a population-representative household survey of four health clinic catchment areas of 1,075 women of reproductive age in 2015. Multivariable logistic regression was used to model individual and structural factors associated with utilization of four maternal and child health services. Key outcomes were: facility-based delivery, maternal postnatal health check by a health professional within the first six weeks of birth, childhood vaccination, and receipt of malaria medication for febrile children under age five within 72 hours of symptom onset. Results 83 percent of women who gave birth in the last 2 years delivered at a health facility. In adjusted models, the strongest predictor of facility delivery in the rural catchment areas was proximity to a health center, with women living under three kilometers having 3.7 (95% CI 1.7, 7.9) times the odds of a facility birth. Only 11 percent of women received a health check by a health provider at any time in the postnatal period. Postnatal health checks were less likely for women in the poorest households and for women who resided in rural areas. Children of polygamous mothers had half the odds of receiving malaria medication for fever within 72 hours of symptom onset, while children with increased household wealth status had increased odds of childhood vaccination and receiving treatment for malaria. Conclusion Our analysis highlights the importance of risk stratification analysis to inform the delivery and scope of maternal and child health programs needed to reach those with the least access to care. PMID:28301539

  16. Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients.

    PubMed

    Demir, Münevver; Grünewald, Friederike; Lang, Sonja; Schramm, Christoph; Bowe, Andrea; Mück, Vera; Kütting, Fabian; Goeser, Tobias; Steffen, Hans-Michael

    2016-09-01

    We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool.

  17. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse.

    PubMed

    Leonardi, Daiana B; Abbate, Mercedes; Riccheri, María C; Nuñez, Myriam; Alfonso, Graciela; Gueron, Geraldine; De Siervi, Adriana; Vazquez, Elba; Cotignola, Javier

    2017-01-03

    The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03-6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17-8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09-7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14-7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths.

  18. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

    PubMed Central

    Riccheri, María C.; Nuñez, Myriam; Alfonso, Graciela; Gueron, Geraldine; De Siervi, Adriana; Vazquez, Elba; Cotignola, Javier

    2017-01-01

    The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03–6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17–8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09–7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14–7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths. PMID:27058755

  19. Do We Know Whether Researchers and Reviewers are Estimating Risk and Benefit Accurately?

    PubMed

    Hey, Spencer Phillips; Kimmelman, Jonathan

    2016-10-01

    Accurate estimation of risk and benefit is integral to good clinical research planning, ethical review, and study implementation. Some commentators have argued that various actors in clinical research systems are prone to biased or arbitrary risk/benefit estimation. In this commentary, we suggest the evidence supporting such claims is very limited. Most prior work has imputed risk/benefit beliefs based on past behavior or goals, rather than directly measuring them. We describe an approach - forecast analysis - that would enable direct and effective measure of the quality of risk/benefit estimation. We then consider some objections and limitations to the forecasting approach.

  20. Usefulness of quantitative versus qualitative ST-segment depression for risk stratification of non-ST elevation acute coronary syndromes in contemporary clinical practice.

    PubMed

    Yan, Raymond T; Yan, Andrew T; Granger, Christopher B; Lopez-Sendon, Jose; Brieger, David; Kennelly, Brian; Budaj, Andrzej; Steg, Ph Gabriel; Georgescu, Alina A; Hassan, Quamrul; Goodman, Shaun G

    2008-04-01

    This aim of this study was to assess the clinical utility of quantitative ST-segment depression (STD) for refining the risk stratification of non-ST elevation acute coronary syndromes in the prospective, multinational Global Registry of Acute Coronary Events (GRACE). Quantitative measurements of STD on admission electrocardiograms were evaluated independently by a core laboratory, and their predictive value for in-hospital and cumulative 6-month mortality was examined. Although more severe STD is a marker of increased short- and long-term mortality, it is also associated with higher risk clinical features and biomarkers. Thus, after adjustment for these clinically important predictors, quantitative STD does not provide incremental prognostic value beyond simple dichotomous evaluation for the presence of STD. Furthermore, adopting quantitative instead of the prognostically proven qualitative evaluation of STD does not improve risk discrimination afforded by the validated GRACE risk models. In conclusion, the findings do not support the quantification of STD in routine clinical practice beyond simple evaluation for the presence of STD as an integral part of comprehensive risk stratification using the GRACE risk score.

  1. The Value of Elastic Modulus Index as a Novel Surrogate Marker for Cardiovascular Risk Stratification by Dimensional Speckle-Tracking Carotid Ultrasonography

    PubMed Central

    Yoon, Ji Hyun; Cho, In-Jeong; Sung, Ji Min; Lee, Jinyong; Ryoo, Hojin; Shim, Chi Young; Hong, Geu-Ru; Chung, Namsik

    2016-01-01

    Background Carotid intima media thickness (CIMT) and the presence of carotid plaque have been used for risk stratification of cardiovascular disease (CVD). To date, however, the association between multi-directional functional properties of carotid artery and CVD has not been fully elucidated. We sought to explore the multi-directional mechanics of the carotid artery in relation to cardiovascular risk. Methods Four hundred one patients who underwent carotid ultrasound were enrolled between January 2010 and April 2013. A high risk of CVD was defined as more than 20% of 10-year risk based on the Framingham risk score. Using a speckle-tracking technique, the longitudinal and radial movements were analyzed in the B-mode images. Peak longitudinal and radial displacements, strain and strain rate were also measured. Beta stiffness and elastic modulus index were calculated from the radial measurements. Results Of the overall sample, 13% (52) of patients comprised the high-risk group. In multivariate logistic regression, CIMT and elastic modulus index were independently associated with a high-risk of CVD {odds ratio (OR): 1.810 [95% confidence interval (CI) 1.249–2.622] and OR: 1.767 (95% CI: 1.177–2.652); p = 0.002, 0.006, respectively}. The combination of CIMT and elastic modulus index correlated with a high-risk of CVD more so than CIMT alone. Conclusion The elastic modulus index of the carotid artery might serve as a novel surrogate marker of high-risk CVD. Measurement of the multi-directional mechanics of the carotid artery using the speckle tracking technique has potential for providing further information over conventional B-mode ultrasound for stratification of CVD risk. PMID:27721952

  2. 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

  3. Post-operative stimulated thyroglobulin and neck ultrasound as personalized criteria for risk stratification and radioactive iodine selection in low- and intermediate-risk papillary thyroid cancer.

    PubMed

    Orlov, Steven; Salari, Farnaz; Kashat, Lawrence; Freeman, Jeremy L; Vescan, Allan; Witterick, Ian J; Walfish, Paul G

    2015-09-01

    The purpose of this study was to demonstrate the utility of a personalized risk stratification and radioactive iodine (RAI) selection protocol (PRSP) using post-operative stimulated thyroglobulin (Stim-Tg) and neck ultrasound in low- and intermediate-risk papillary thyroid carcinoma (PTC) patients. Patients with PTC tumors ≥1 cm were prospectively followed after total thyroidectomy and selective therapeutic central compartment neck dissection. Low/intermediate risk was defined as PTC confined to the thyroid or central (level VI) lymph nodes. Stim-Tg and neck ultrasound were performed approximately 3 months after surgery and used to guide RAI selection. Patients with Stim-Tg < 1 µg/L did not receive RAI, while those with Stim-Tg >5 µg/L routinely did. Those with Stim-Tg 1-5 µg/L received RAI on the basis of several clinical risk factors. Patients were followed for >6 years with serial neck ultrasound and basal/stimulated thyroglobulin. Among the 129 patients, 84 (65 %) had undetectable Stim-Tg after initial surgery, 40 (31 %) had Stim-Tg of 1-5 µg/L, and 5 (4 %) had Stim-Tg >5 µg/L. RAI was administered to 8 (20 %) patients with Stim-Tg 1-5 µg/L and 5 (100 %) with Stim-Tg >5 µg/L. Using this approach, RAI therapy was avoided in 17/20 (85 %) patients with tumors >4 cm, in 72/81 (89 %) patients older than 45 years, and in 6/9 (67 %) patients with central lymph node involvement. To date, 116 (90 %) patients in this cohort have not received RAI therapy with no evidence of residual/recurrent disease, whereas among the 13 patients who received RAI, 1 (8 %) had pathologic residual/recurrence disease. Using the proposed PRSP, RAI can be avoided in the majority of low/intermediate-risk PTC patients. Moreover, traditional risk factors considered to favor RAI treatment were not always concordant with the PRSP and may lead to overtreatment.

  4. Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy.

    PubMed

    Diotti, Roberta Antonia; Mancini, Nicasio; Clementi, Nicola; Sautto, Giuseppe; Moreno, Guisella Janett; Criscuolo, Elena; Cappelletti, Francesca; Man, Petr; Forest, Eric; Remy, Louise; Giannecchini, Simone; Clementi, Massimo; Burioni, Roberto

    2014-08-01

    JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment.

  5. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study.

    PubMed

    von Rundstedt, Friedrich-Carl; Mata, Douglas A; Kryvenko, Oleksandr N; Shah, Anup A; Jhun, Iny; Lerner, Seth P

    2017-01-27

    Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30-40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall

  6. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study

    PubMed Central

    von Rundstedt, Friedrich-Carl; Mata, Douglas A.; Kryvenko, Oleksandr N.; Shah, Anup A.; Jhun, Iny; Lerner, Seth P.

    2016-01-01

    Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30–40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall

  7. Development and applications of the Veterans Health Administration's Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdose and suicide.

    PubMed

    Oliva, Elizabeth M; Bowe, Thomas; Tavakoli, Sara; Martins, Susana; Lewis, Eleanor T; Paik, Meenah; Wiechers, Ilse; Henderson, Patricia; Harvey, Michael; Avoundjian, Tigran; Medhanie, Amanuel; Trafton, Jodie A

    2017-02-01

    Concerns about opioid-related adverse events, including overdose, prompted the Veterans Health Administration (VHA) to launch an Opioid Safety Initiative and Overdose Education and Naloxone Distribution program. To mitigate risks associated with opioid prescribing, a holistic approach that takes into consideration both risk factors (e.g., dose, substance use disorders) and risk mitigation interventions (e.g., urine drug screening, psychosocial treatment) is needed. This article describes the Stratification Tool for Opioid Risk Mitigation (STORM), a tool developed in VHA that reflects this holistic approach and facilitates patient identification and monitoring. STORM prioritizes patients for review and intervention according to their modeled risk for overdose/suicide-related events and displays risk factors and risk mitigation interventions obtained from VHA electronic medical record (EMR)-data extracts. Patients' estimated risk is based on a predictive risk model developed using fiscal year 2010 (FY2010: 10/1/2009-9/30/2010) EMR-data extracts and mortality data among 1,135,601 VHA patients prescribed opioid analgesics to predict risk for an overdose/suicide-related event in FY2011 (2.1% experienced an event). Cross-validation was used to validate the model, with receiver operating characteristic curves for the training and test data sets performing well (>.80 area under the curve). The predictive risk model distinguished patients based on risk for overdose/suicide-related adverse events, allowing for identification of high-risk patients and enrichment of target populations of patients with greater safety concerns for proactive monitoring and application of risk mitigation interventions. Results suggest that clinical informatics can leverage EMR-extracted data to identify patients at-risk for overdose/suicide-related events and provide clinicians with actionable information to mitigate risk. (PsycINFO Database Record

  8. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial.

    PubMed

    Zhu, Hong-Hu; Zhang, Xiao-Hui; Qin, Ya-Zhen; Liu, Dai-Hong; Jiang, Hao; Chen, Huan; Jiang, Qian; Xu, Lan-Ping; Lu, Jin; Han, Wei; Bao, Li; Wang, Yu; Chen, Yu-Hong; Wang, Jing-Zhi; Wang, Feng-Rong; Lai, Yue-Yun; Chai, Jun-Yue; Wang, Li-Ru; Liu, Yan-Rong; Liu, Kai-Yan; Jiang, Bin; Huang, Xiao-Jun

    2013-05-16

    We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P = .001). Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P = .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR-OCH-12002406.

  9. Clinical use of high mobility group box 1 and the receptor for advanced glycation end products in the prognosis and risk stratification of heart failure: a literature review.

    PubMed

    Marsh, Amanda M; Nguyen, Austin Huy; Parker, Taylor M; Agrawal, Devendra K

    2017-03-01

    Heart failure (HF) is a clinical syndrome that represents the end stage of heart disease and remains the leading cause of morbidity and mortality worldwide. As heart failure mortality rates remain elevated, additional biomarkers that facilitate early detection or risk stratification in HF is of particularly great interest. High mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) cause the activation of intracellular signaling, gene expression, and production of inflammatory cytokines and have been linked to many inflammatory disease states such as diabetes mellitus and atherosclerosis. Few studies have investigated their role in the pathophysiology of HF and any significant correlation remains uncertain. Review of the available literature discussing HMGB1 and RAGE clinical values as independent prognostic variables in HF resulted in the inclusion of 11 studies, which enrolled a total of 2025 heart failure patients. Overall, the data suggests a statistically significant positive correlation between RAGE and HF, with increasing RAGE levels associated with increasing New York Heart Association (NYHA) functional class of heart failure. HMGB1 correlations were not as extensively studied, but there is evidence that both HMGB1 and RAGE have a definite potential as biomarkers for the prognosis and risk stratification of HF patients.

  10. Risk Stratification For Axillary Lymph Node Metastases in Breast Cancer Patients: What Clinicopathological and Radiological Factors of Primary Breast Cancer Can Predict Preoperatively Axillary Lymph Node Metastases?

    PubMed

    Yun, Seong Jong; Sohn, Yu-Mee; Seo, Mirinae

    2017-03-01

    This study was to investigate clinicopathological features including immunohistochemical subtype and radiological factors of primary breast cancer to predict axillary lymph node metastasis (ALNM) and preoperative risk stratification.From June 2004 to May 2014, 369 breast cancer patients (mean age, 54.7 years; range, 29-82 years) who underwent surgical axillary node sampling were included. Two radiologists retrospectively reviewed clinicopathological features, initial mammography, and initial breast ultrasonography (US). Univariate and multivariate logistic regression analyses were used to evaluate associations between ALNM and variables. Odds ratio with 95% confidence interval and risk of ALNM were calculated.Among 369 patients, 117 (31.7%) had ALNM and 252 (68.3%) had no ALNM revealed surgically. On multivariate analysis, four factors showed positive association with ALNM: the presence of symptoms (P < 0.001), triple-negative breast cancer subtype (P = 0.001), mass size on US (>10 mm, P < 0.001), and Breast Imaging Reporting and Data System category on US (≥4c, P < 0.001). The significant risk of ALNM was particularly seen in patients with two or more factors (2, P = 0.013; 3, P < 0.001; 4, P < 0.001).The estimated risks of ALNM increased in patients with two, three, and four factors with odds ratios of 5.5, 14.3, and 60.0, respectively.The presence of symptoms, triple-negative breast cancer subtype, larger size mass on US (>10 mm), and higher Breast Imaging Reporting and Data System category on US (≥4c) were positively associated with ALNM. Radiologically, US findings are significant factors that can affect the decision making process regarding ALNM. Based on risk stratification, the possibility of ALNM can be better predicted if 2 or more associated factors existed preoperatively.

  11. 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.

  12. A Simple Risk Stratification Model for ST-Elevation Myocardial Infarction (STEMI) from the Combination of Blood Examination Variables: Acute Myocardial Infarction-Kyoto Multi-Center Risk Study Group

    PubMed Central

    Nakamura, Takeshi; Yokota, Isao; Zen, Kan; Yamano, Tetsuhiro; Shiraishi, Hirokazu; Shiraishi, Jun; Sawada, Takahisa; Kohno, Yoshio; Kitamura, Makoto; Furukawa, Keizo; Matoba, Satoaki

    2016-01-01

    Background Many mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice. Methods and Findings We developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/μL, <10 g/dL, >1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened in-hospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the in-hospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II substudy; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01). Conclusions This laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index. PMID

  13. Risk stratification, treatment selection, and transplant eligibility in multiple myeloma: a qualitative study of the perspectives and self-reported practices of oncologists

    PubMed Central

    LeBlanc, T.W.; Howson, A.; Turell, W.; Sheldon, P.; Locke, S.C.; Tuchman, S.A.; Gasparetto, C.; Kaura, S.; Khan, Z.M.; Abernethy, A.P.

    2016-01-01

    Background Since the early 2000s, treatment options for multiple myeloma have rapidly expanded, adding significant complexity to the management of this disease. To our knowledge, no systematic qualitative research on clinical decision-making in multiple myeloma has been published. We sought to characterize how physicians view and implement guidelines and incorporate novel approaches into patient care. Methods We designed a semi-structured qualitative interview guide informed by literature review and an expert advisory panel. We conducted 60-minute interviews with a diverse sample of oncology physicians in the southeast United States. We used a constant comparative method to code and analyze interview transcripts. The research team and advisory panel discussed and validated emergent themes. Results Participants were 13 oncologists representing 5 academic and 4 community practices. Academic physicians reported using formal risk-stratification schemas; community physicians typically did not. Physicians also described differences in eligibility criteria for transplantation; community physicians emphasized distance, social support, and psychosocial capacity in making decisions about transplantation referral; the academic physicians reported using more specific clinical criteria. All physicians reported using a maintenance strategy both for post-transplant and for transplant-ineligible patients; however, determining the timing of maintenance therapy initiation and the response were reported as challenging, as was recognition or definition of relapse, especially in terms of when treatment re-initiation is indicated. Conclusions Practices reported by both academic and community physicians suggest opportunities for interventions to improve patient care and outcomes through optimal multiple myeloma management and therapy selection. Community physicians in particular might benefit from targeted education interventions about risk stratification, transplant eligibility, and

  14. Risk-benefit stratification as a guide to lidocaine prophylaxis of primary ventricular fibrillation in acute myocardial infarction: an analytic review.

    PubMed Central

    Goldman, L.; Batsford, W. P.

    1979-01-01

    Early investigators suggested that ventricular fibrillation without heart failure in acute myocardial infarction was reliably preceded by warning arrhythmias, and that suppression of such arrhythmias with intravenous lidocaine could avoid the need for resuscitation. While the efficacy and safety of lidocaine have been substantiated, the reliability of warning arrhythmias as predictors for primary ventricular fibrillation has not. We present data showing that the risk of primary ventricular fibrillation is most dependent on the patient's age and the interval since the onset of his symptoms, rather than on the presence of warning arrhythmias. We have estimated that lidocaine prophylaxis would have to be given to about 12 patients in the highest risk group (patients under age 50 and within six hours of the onset of symptoms), compared to about 400 patients in the lowest risk group (patients above age 70 and more than 24 hours since the onset of symptoms), to prevent one episode of primary ventricular fibrillation in each group. We propose that these risk stratifications, as adapted to the conditions in specific hospitals, provide the most rational approach to lidocaine prophylaxis of primary ventricular fibrillation. PMID:392960

  15. 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.

  16. Risk Stratification in Cervical Cancer Screening by Complete Screening History- Applying Bioinformatics to a General Screening Population.

    PubMed

    Baltzer, Nicholas; Sundström, Karin; Nygård, Jan F; Dillner, Joakim; Komorowski, Jan

    2017-04-06

    Women screened for cervical cancer in Sweden are currently treated under a one-size-fits-all programme, which has been successful in reducing the incidence of cervical cancer but does not use all of the participants' available medical information. This study aimed to use women's complete cervical screening histories to identify diagnostic patterns that may indicate an increased risk of developing cervical cancer. A nationwide case-control study was performed where cervical cancer screening data from 125,476 women with a maximum follow-up of 10 years were evaluated for patterns of SNOMED diagnoses. The cancer development risk was estimated for a number of different screening history patterns and expressed as Odds Ratios (OR), with a history of 4 benign cervical tests as reference, using logistic regression. The overall performance of the model was moderate (64% accuracy, 71% Area Under Curve (AUC)) with 61-62% of the study population showing no specific patterns associated with risk. However, predictions for high-risk groups as defined by screening history patterns were highly discriminatory with ORs ranging from 8 to 36. The model for computing risk performed consistently across different screening history lengths, and several patterns predicted cancer outcomes. The results show the presence of risk-increasing and risk-decreasing factors in the screening history. Thus it is feasible to identify subgroups based on their complete screening histories. Several high-risk subgroups identified might benefit from an increased screening density. Some low-risk subgroups identified could likely have a moderately reduced screening density without additional risk. This article is protected by copyright. All rights reserved.

  17. Risk Stratification using Human Papillomavirus Testing among Women with Equivocally Abnormal Cytology: Results from a State-wide Surveillance Program

    PubMed Central

    Gage, Julia C; Hunt, William C; Schiffman, Mark; Katki, Hormuzd A; Cheung, Li C; Cuzick, Jack; Myers, Orrin; Castle, Philip E; Wheeler, Cosette M.

    2016-01-01

    Background Clinical guidelines for cervical cancer screening have incorporated comparative risks of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) for various screening outcomes to determine management. Few cohorts are large enough to distinguish CIN3+ risks among women with minor abnormalities vs. negative cytology because of low incidence. The New Mexico HPV Pap Registry offers a unique opportunity to evaluate cervical cancer screening in a diverse population across a broad-spectrum of health service delivery. Methods Kaplan-Meier and logistic-Weibull survival models were used to estimate cumulative risks of CIN3+ among women aged 21–64 who were screened in New Mexico between 2007–2011 with negative, equivocal or mildly abnormal cytology, i.e., atypical squamous cells of undetermined significance (ASC-US; with or without HPV triage), or low-grade squamous intraepithelial lesions. Results We identified 452,045 women meeting the selection criteria. The 3-year CIN3+ risks for women with negative, ASC-US and LSIL cytology were: 0.30%, 2.6%, and 5.2%, respectively. HPV triage of ASC-US stratified 3-year CIN3+ risks were 0.72% for HPV-negative and 7.7% for HPV-positive. Risks tended to decline after age 30 for all screening results. Conclusions In this state-wide population-based cohort, cytology and HPV triage of ASC-US stratified women’s CIN3+ risk into similar patterns observed previously, suggesting the validity of screening guidelines for diverse populations in the United States (U.S.). Absolute risk estimates should be compared across other large populations. Impact Strategies for HPV triage of ASC-US derived from clinical trials are upheld in large clinical practice settings and across diverse screening populations in the U.S.. PMID:26518316

  18. 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

  19. 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

  20. 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

  1. Use of three-dimensional transesophageal echocardiography to evaluate mitral valve morphology for risk stratification prior to mitral valvuloplasty.

    PubMed

    Francis, Loren; Finley, Alan; Hessami, Walead

    2017-02-01

    Mitral stenosis is often managed percutaneously with an interventional procedure such as balloon commissurotomy. Although this often results in an increased mitral valve area and improved clinical symptoms, this procedure is not benign and may have serious complications including the development of hemodynamically significant mitral valve regurgitation. Multiple scoring systems have been developed to attempt to risk stratify these patients prior to their procedure.

  2. Polymerase chain reaction-assisted papillomavirus detection in cervicovaginal smears: stratification by clinical risk and cytology reports.

    PubMed

    Kühler-Obbarius, C; Milde-Langosch, K; Helling-Giese, G; Salfelder, A; Peimann, C; Löning, T

    1994-01-01

    Seven hundred and twelve patients from cancer screening, pregnancy care, outpatient clinics for patients at risk for cervical dysplasia and human immunodeficiency virus (HIV) infection were tested simultaneously for cytological aberrations and human papillomavirus (HPV). Classification of these cases, and of all cytology records throughout 1991 and 1992 was performed according to the "Münchner Nomenklatur" and the Bethesda classification. HPV-directed polymerase chain reaction analysis was carried out with general primers, patients at risk for cervical dysplasia were tested by subsequent hybridization with HPV 16 and 18 probes. Patients from cancer screening and pregnancy care showed similar HPV prevalences ranging between 19.4%-24.6%. In contrast, patients from dysplasia and HIV units were infected in 56.2%-62.3% and 75.0%-76.9% respectively in centre of disease control stage III-IV, HPV detection rates in patients from dysplasia and HIV units increased gradually from 40.1%-52.9% in non-suspicious smears to 80.8%-100% in atypical smears. High risk HPV 16 and 18 infections were detected in 64% of smears with cytological evidence of HPV infection (koilocytosis) to 84.2% in severe dysplasia. Following the Bethesda guidelines, 2.9%-14.7% of all smears initially reported as Pap 2 K (suggestive of HPV infection) would be qualified as risk lesions (low grade squamous intraepithelial lesions), although they tested HPV negative in more than a third of cases. Thus, when using the Bethesda system, HPV analysis is needed to prevent overclassification and overtreatment. The "Münchner Nomenklatur" avoids this dilemma by not mixing morphological statements on infection, atypia and cancer risk.

  3. 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…

  4. A MicroRNA Panel in Pancreatic Cyst Fluid for the Risk Stratification of Pancreatic Cysts in a Prospective Cohort

    PubMed Central

    Utomo, WK; Looijenga, LH; Bruno, MJ; Hansen, BE; Gillis, AJM; Biermann, K; Peppelenbosch, MP; Fuhler, GM; Braat, H

    2016-01-01

    A subset of pancreatic cystic neoplasms are regarded as precursor lesions of pancreatic cancer, but only a minority of all pancreatic cystic neoplasms will undergo malignant transformation. MicroRNAs are increasingly recognized as molecular targets in carcinogenesis. Previously, a 9-microRNA (miR) signature was suggested to discriminate between high risk and low risk pancreatic cystic neoplasm. In this study, we aimed to validate this 9-miR panel in a prospective cohort. Total miR was isolated from pancreatic cyst fluid and expression of miR18a, miR24, miR30a-3p, miR92a, miR99b, miR106b, miR142-3p, miR342-3p, and miR532-3p was analyzed by singleplex Taqman MicroRNA Assay. A total of 62 patient samples were analyzed. During follow-up, 24 (38.7%) patients underwent resection, of which 6 (9.7%) patients showed at least high grade dysplasia. A logistic regression model presented a “predicted risk” score which significantly differed between low and high risk cysts, either including all patients or only those with histological confirmation of diagnosis. Using a set cut-off of 50%, the sensitivity of the model for the total cohort was 10.0%, specificity 100.0%, positive predicted value 100.0%, negative predicted value 85.2%, and diagnostic accuracy of 85.5%. Thus, while observing a significant difference between low and high risk cysts, clinical implementation of this biomarker panel is as yet unlikely to be beneficial in the management of pancreatic cysts. PMID:28131248

  5. 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

  6. Mutant-specific BRAF and CD117 immunocytochemistry potentially facilitate risk stratification for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens.

    PubMed

    Meng, Zhilan; Lu, Junliang; Wu, Huanwen; Zhao, Yu; Luo, Yufeng; Gao, Jie; Zhu, Qingli; Jiang, Yuxin; Li, Wenbo; Liang, Zhiyong

    2016-01-01

    The study aims to test whether combination of mutant-specific BRAF and CD117 immunocytochemical (ICC) staining stratifies probability for papillary thyroid carcinoma (PTC) in thyroid fine-needle aspiration biopsy (FNAB) specimens. A consecutive cohort of cases diagnosed as atypia of undetermined significance (AUS) or suspicious for malignancy-suspicious for papillary thyroid carcinoma (SM-SPTC) from 30 December, 2011 to 23 October, 2014 in a single institute was enrolled. Forty cytologically benign and 50 cytologically diagnosed PTC within the same time span were also included. CD117 and mutant-specific BRAF (BRAF VE1) ICC staining was performed. Association of BRAF VE1 and CD117 expression with final diagnosis was analyzed. Both BRAF VE1 and CD117 showed good performance in distinguishing PTC from benign nodules. Combination of BRAF VE1 and CD117 stratified 180 cases into three categories: BRAF VE1 positive regardless of CD117 expression (ICC-malignant), BRAF VE1 negative plus low level of CD117 expression (ICC-intermediate), and BRAF VE1 negative plus high level of CD117 expression (ICC-benign), which was associated with 100, 75.6, and 0 % of malignancy. Combination of mutant-specific BRAF and CD117 ICC may potentially facilitate the PTC risk stratification in FNAB thyroid nodule specimens.

  7. 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.

  8. Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

    SciTech Connect

    Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2012-09-01

    Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size {>=}2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.

  9. 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

  10. The Burden of Hard Atherosclerotic Plaques Does Not Promote Endoleak Development After Endovascular Aortic Aneurysm Repair: A Risk Stratification

    SciTech Connect

    Petersen, Johannes Glodny, Bernhard

    2011-10-15

    Purpose: To objectify the influence of the atherosclerotic burden in the proximal landing zone on the development of endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) or thoracic endovascular aneurysm repair (TEVAR) using objective aortic calcium scoring (ACS). Materials and Methods: This retrospective observation study included 267 patients who received an aortic endograft between 1997 and 2010 and for whom preoperative computed tomography (CT) was available to perform ACS using the CT-based V600 method. The mean follow-up period was 2 {+-} 2.3 years. Results: Type I endoleaks persisted in 45 patients (16.9%), type II in 34 (12.7%), type III in 8 (3%), and type IV or V in 3 patients, respectively (1.1% each). ACS in patients with type I endoleaks was not increased: 0.029 {+-} 0.061 ml compared with 0.075 {+-} 0.1349 ml in the rest of the patients, (p > 0.05; Whitney-Mann U-Test). There were significantly better results for the indication 'traumatic aortic rupture' than for the other indications (p < 0.05). In multivariate logistic regression analyses, age was an independent risk factor for the development of type I endoleaks in the thoracic aorta (Wald 9.5; p = 0.002), whereas ACS score was an independent protective factor (Wald 6.9; p = 0.009). In the abdominal aorta, neither age nor ACS influenced the development of endoleaks. Conclusion: Contrary to previous assumptions, TEVAR and EVAR can be carried out without increasing the risk of an endoleak of any type, even if there is a high atherosclerotic 'hard-plaque' burden of the aorta. The results are significantly better for traumatic aortic.

  11. 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

  12. A retrospective study of ultrasound and FNA cytology investigation of thyroid nodules: working towards combined risk stratification.

    PubMed

    Liu, Zi Wei; Fox, Richard; Unadkat, Samit; Farrell, Roy

    2017-03-10

    The British Thyroid Association recommended in new guidelines on thyroid cancer treatment [Kwak et al. (Korean J Radiol 14:110-117, 2013)] that ultrasound grading of thyroid nodules should be incorporated into MDT management. A retrospective study was carried out to determine that the impact of US grading has had on MDT decision making in practice. The design used in the study is a retrospective review of case notes. The study was carried out in the hub hospital for thyroid cancer in the North west London Cancer network. We included consecutive patients referred to the regional thyroid multidisciplinary meeting between August 2014 and May 2015 for investigation of thyroid nodules. Data were collected on patient demographics, co-morbidity, thy grading, ultrasound grading, surgery, post-operative histology, and radioactive iodine treatment details. Accuracy of cytology and ultrasound in diagnosing malignancy was correlated to definitive histology. 99 patients with thyroid nodules were included in the study. 97% of patients had at least one fine needle aspiration and 75% had ultrasound grading. Thy3f (Bethesda IV) nodules were more likely to be carcinoma if associated with a U4 grade rather than U3 (67 vs 18%, p = 0.028). Ultrasound grading has recently been introduced to the standard practice in investigation of thyroid nodules. Further assessment of the accuracy of ultrasound grading in clinical practice may allow us to risk-stratify thy3a/thy3f (Bethesda III/IV) lesions and personalise treatment.

  13. The Your Disease Risk Index for colorectal cancer is an inaccurate risk stratification tool for advanced colorectal neoplasia at screening colonoscopy.

    PubMed

    Schroy, Paul C; Coe, Alison M; Mylvaganam, Shamini R; Ahn, Lynne B; Lydotes, Maria A; Robinson, Patricia A; Davis, Julie T; Chen, Clara A; Ashba, Jacqueline; Atkinson, Michael L; Colditz, Graham A; Heeren, Timothy C

    2012-08-01

    Tailoring the use of screening colonoscopy based on the risk of advanced colorectal neoplasia (ACN) could optimize the cost-effectiveness of colorectal cancer (CRC) screening. Our goal was to assess the accuracy of the Your Disease Risk (YDR) CRC risk index for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN. The YDR risk assessment tool was administered to 3,317 asymptomatic average risk patients 50 to 79 years of age just before their screening colonoscopy. Associations between YDR-derived relative risk (RR) scores and ACN prevalence were examined using logistic regression and χ(2) analyses. ACN was defined as a tubular adenoma ≥1 cm, tubulovillous or villous adenoma of any size, and the presence of high-grade dysplasia or cancer. The overall prevalence of ACN was 5.6%. Although YDR-derived RR scores were linearly associated with ACN after adjusting for age and gender (P = 0.033), the index was unable to discriminate "below average" from "above/average" risk patients [OR, 1.01; 95% confidence interval (CI), 0.75-1.37]. Considerable overlap in rates of ACN was also observed between the different YDR risk categories in our age- and gender-stratified analyses. The YDR index lacks accuracy for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN.

  14. Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery

    PubMed Central

    Lim, Chetana; Compagnon, Philippe; Sebagh, Mylène; Salloum, Chady; Calderaro, Julien; Luciani, Alain; Pascal, Gérard; Laurent, Alexis; Levesque, Eric; Maggi, Umberto; Feray, Cyrille; Cherqui, Daniel; Castaing, Denis; Azoulay, Daniel

    2015-01-01

    Objectives Appropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC. Methods The outcomes of 149 patients with huge HCCs who underwent resection during 1995–2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility. Results Independent predictors of 3-month mortality (18.1%) were: total bilirubin level <34 μmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1-year recurrence-related mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease. Conclusions According to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery. PMID:25980326

  15. 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

  16. Time-dependent propensity score and collider-stratification bias: an example of beta2-agonist use and the risk of coronary heart disease.

    PubMed

    Sanni Ali, M; Groenwold, Rolf H H; Pestman, Wiebe R; Belitser, Svetlana V; Hoes, Arno W; de Boer, A; Klungel, Olaf H

    2013-04-01

    Stratification and conditioning on time-varying cofounders which are also intermediates can induce collider-stratification bias and adjust-away the (indirect) effect of exposure. Similar bias could be expected when one conditions on time-dependent PS. We explored collider-stratification and confounding bias due to conditioning or stratifying on time-dependent PS using a clinical example on the effect of inhaled short- and long-acting beta2-agonist use (SABA and LABA, respectively) on coronary heart disease (CHD). In an electronic general practice database we selected a cohort of patients with an indication for SABA and/or LABA use and ascertained potential confounders and SABA/LABA use per three month intervals. Hazard ratios (HR) were estimated using PS stratification as well as covariate adjustment and compared with those of Marginal Structural Models (MSMs) in both SABA and LABA use separately. In MSMs, censoring was accounted for by including inverse probability of censoring weights.The crude HR of CHD was 0.90 [95 % CI: 0.63, 1.28] and 1.55 [95 % CI: 1.06, 2.62] in SABA and LABA users respectively. When PS stratification, covariate adjustment using PS, and MSMs were used, the HRs were 1.09 [95 % CI: 0.74, 1.61], 1.07 [95 % CI: 0.72, 1.60], and 0.86 [95 % CI: 0.55, 1.34] for SABA, and 1.09 [95 % CI: 0.74, 1.62], 1.13 [95 % CI: 0.76, 1.67], 0.77 [95 % CI: 0.45, 1.33] for LABA, respectively. Results were similar for different PS methods, but higher than those of MSMs. When treatment and confounders vary during follow-up, conditioning or stratification on time-dependent PS could induce substantial collider-stratification or confounding bias; hence, other methods such as MSMs are recommended.

  17. Natural history of definitive diverticular hemorrhage based upon stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis

    PubMed Central

    Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O.G.; Jutabha, Rome; Ghassemi, Kevin; Dulai, Gareth S.; Machicado, Gustavo A.

    2015-01-01

    BACKGROUND AND AIMS Few prospective reports describe the short term natural history of colon diverticular hemorrhage based upon stigmata of recent hemorrhage and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes are to report the 30 day natural history of definitive diverticular hemorrhage based upon stigmata and to describe Doppler probe blood flow detection and as a guide to definitive hemostasis. METHODS Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30 day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. Natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after washing away clots are reported. Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis is also reported in a recent cohort. RESULTS For natural history patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. Doppler probe detected arterial blood flow in 92% of major stigmata, none after hemostasis and no one rebled. CONCLUSIONS 1. Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. 2. Patients with clean diverticula or only flat spots had no rebleeding. 3. High rates of arterial blood flow were detected under major stigmata with Doppler probe but with obliteration by hemostasis no rebleeding occurred. PMID:26227931

  18. 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.

  19. 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),…

  20. Aggregate versus individual-level sexual behavior assessment: how much detail is needed to accurately estimate HIV/STI risk?

    PubMed

    Pinkerton, Steven D; Galletly, Carol L; McAuliffe, Timothy L; DiFranceisco, Wayne; Raymond, H Fisher; Chesson, Harrell W

    2010-02-01

    The sexual behaviors of HIV/sexually transmitted infection (STI) prevention intervention participants can be assessed on a partner-by-partner basis: in aggregate (i.e., total numbers of sex acts, collapsed across partners) or using a combination of these two methods (e.g., assessing five partners in detail and any remaining partners in aggregate). There is a natural trade-off between the level of sexual behavior detail and the precision of HIV/STI acquisition risk estimates. The results of this study indicate that relatively simple aggregate data collection techniques suffice to adequately estimate HIV risk. For highly infectious STIs, in contrast, accurate STI risk assessment requires more intensive partner-by-partner methods.

  1. 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

  2. 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

  3. Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score

    PubMed Central

    2012-01-01

    hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs. PMID:22874067

  4. Risk stratification of early admission to the intensive care unit of patients with no major criteria of severe community-acquired pneumonia: development of an international prediction rule

    PubMed Central

    Renaud, Bertrand; Labarère, José; Coma, Eva; Santin, Aline; Hayon, Jan; Gurgui, Mercé; Camus, Nicolas; Roupie, Eric; Hémery, François; Hervé, Jérôme; Salloum, Mirna; Fine, Michael J; Brun-Buisson, Christian

    2009-01-01

    Introduction To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3. Methods Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support). Results A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population. Conclusions The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions. PMID:19358736

  5. Ambulatory blood pressure monitoring: importance of sampling rate and duration--48 versus 24 hours--on the accurate assessment of cardiovascular risk.

    PubMed

    Hermida, Ramón C; Ayala, Diana E; Fontao, María J; Mojón, Artemio; Fernández, José R

    2013-03-01

    Independent prospective studies have found that ambulatory blood pressure (BP) monitoring (ABPM) is more closely correlated with target organ damage and cardiovascular disease (CVD) risk than clinic BP measurement. This is based on studies in which BP was sampled every 15-30 min for ≤24 h, without taking into account that reproducibility of any estimated parameter from a time series to be potentially used for CVD risk assessment might depend more on monitoring duration than on sampling rate. Herein, we evaluated the influence of duration (48 vs. 24 h) and sampling rate of BP measurements (form every 20-30 min up to every 2 h) on the prognostic value of ABPM-derived parameters. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6 ± 14.5 yrs of age, during a median follow-up of 5.6 yrs. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. At baseline, BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h, and physical activity was simultaneously monitored every min by wrist actigraphy to accurately derive the awake and asleep BP means. Identical assessment was scheduled annually and more frequently (quarterly) if treatment adjustment was required. ABPM profiles were modified to generate time series of identical 48-h duration but with data sampled at 1- or 2-h intervals, or shorter, i.e., first 24 h, time series with data sampled at the original rate (daytime 20-min intervals/nighttime 30-min intervals). Bland-Altman plots indicated that the range of individual differences in the estimated awake and asleep systolic (SBP) and diastolic BP (DBP) means between the original and modified ABPM profiles was up to 3-fold smaller for data sampled every 1 h for 48 h than for data sampled every 20-30 min for the first 24 h. Reduction of ABPM duration to just 24 h resulted in error of the

  6. Stratification of lakes

    NASA Astrophysics Data System (ADS)

    Boehrer, Bertram; Schultze, Martin

    2008-06-01

    Many lakes show vertical stratification of their water masses, at least for some extended time periods. Density differences in water bodies facilitate an evolution of chemical differences with many consequences for living organisms in lakes. Temperature and dissolved substances contribute to density differences in water. The atmosphere imposes a temperature signal on the lake surface. As a result, thermal stratification can be established during the warm season if a lake is sufficiently deep. On the contrary, during the cold period, surface cooling forces vertical circulation of water masses and removal of gradients of water properties. However, gradients of dissolved substances may be sustained for periods much longer than one annual cycle. Such lakes do not experience full overturns. Gradients may be a consequence of external inflows or groundwater seepage. In addition, photosynthesis at the lake surface and subsequent decomposition of organic material in the deeper layers of a lake can sustain a gradient of dissolved substances. Three more geochemical cycles, namely, calcite precipitation, iron cycle, and manganese cycle, are known for sustaining meromixis. A limited number of lakes do not experience a complete overturn because of pressure dependence of temperature of maximum density. Such lakes must be sufficiently deep and lie in the appropriate climate zone. Although these lakes are permanently stratified, deep waters are well ventilated, and chemical differences are small. Turbulent mixing and convective deep water renewal must be very effective. As a consequence, these lakes usually are not termed meromictic. Permanent stratification may also be created by episodic partial recharging of the deep water layer. This mechanism resembles the cycling of the ocean: horizontal gradients result from gradients at the surface, such as differential cooling or enhanced evaporation in adjacent shallow side bays. Dense water parcels can be formed which intrude the deep

  7. Oncological results, functional outcomes and health-related quality-of-life in men who received a radical prostatectomy or external beam radiation therapy for localized prostate cancer: a study on long-term patient outcome with risk stratification.

    PubMed

    Takizawa, Itsuhiro; Hara, Noboru; Nishiyama, Tsutomu; Kaneko, Masaaki; Hoshii, Tatsuhiko; Tsuchida, Emiko; Takahashi, Kota

    2009-05-01

    Health-related quality-of-life (HRQOL) after a radical prostatectomy (RP) or external beam radiation therapy (EBRT) has not been studied in conjunction with oncological outcomes in relation to disease risk stratification. Moreover, the long-term outcomes of these treatment approaches have not been studied. We retrospectively analyzed oncological outcomes between consecutive patients receiving RP (n=86) and EBRT (n=76) for localized prostate cancer. HRQOL and functional outcomes could be assessed in 62 RP (79%) and 54 EBRT (79%) patients over a 3-year follow-up period (median: 41 months) using the Medical Outcomes Study Short Form-36 (SF-36) and the University of California Los Angeles Prostate Cancer Index (UCLA PCI). The 5-year biochemical progression-free survival did not differ between the RP and EBRT groups for low-risk (74.6% vs. 75.0%, P=0.931) and intermediate-risk (61.3% vs. 71.1%, P=0.691) patients. For high-risk patients, progression-free survival was lower in the RP group (45.1%) than in the EBRT group (79.7%) (P=0.002). The general HRQOL was comparable between the two groups. Regarding functional outcomes, the RP group reported lower scores on urinary function and less urinary bother and sexual bother than the EBRT group (P<0.001, P<0.05 and P<0.001, respectively). With risk stratification, the low- and intermediate-risk patients in the RP group reported poorer urinary function than patients in the EBRT group (P<0.001 for each). The sexual function of the high-risk patients in the EBRT group was better than that of the same risk RP patients (P<0.001). Biochemical recurrence was not associated with the UCLA PCI score in either group. In conclusion, low- to intermediate-risk patients treated with an RP may report relatively decreased urinary function during long-term follow-up. The patient's HRQOL after treatment did not depend on biochemical recurrence.

  8. Propellant thermal stratification

    NASA Technical Reports Server (NTRS)

    Winstead, T. W.

    1971-01-01

    The term thermal stratification is used to express nonuniform heat distribution within the bulk propellant. The nonuniform distribution of heat results in significant temperature variations in booster propulsion propellants and causes an undesirable increase in the self-pressurization rate of cryogen storage systems. A semiempirical prediction method has been developed for high gravity environments and is adequate for design purposes; model accuracy is somewhat limited to similarity in tank geometries, and additional work is needed to extend the correlation range. Several low gravity environment models that cover a broad range of predicted results have been developed. There are no applicable data by which any of these models may be selected in preference over the others.

  9. Clinical risk stratification in the emergency department predicts long-term cardiovascular outcomes in a population-based cohort presenting with acute chest pain: primary results of the Olmsted county chest pain study.

    PubMed

    Farkouh, Michael E; Aneja, Ashish; Reeder, Guy S; Smars, Peter A; Bansilal, Sameer; Lennon, Ryan J; Wiste, Heather J; Razzouk, Louai; Traverse, Kay; Holmes, David R; Mathew, Verghese

    2009-09-01

    The long-term cardiovascular outcomes of a population-based cohort presenting to the emergency department (ED) with chest pain and classified with a clinical risk stratification algorithm are not well documented. The Olmsted County Chest Pain Study is a community-based study that included all consecutive patients presenting with chest pain consistent with unstable angina presenting to all EDs in Olmsted County, Minnesota. Patients were classified according to the Agency for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation myocardial infarction and chest pain of noncardiac origin were excluded. Main outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through a median of 16.6 years.The 2271 patients were classified as follows: 436 (19.2%) as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk. Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3 years, significantly more MACCE were recorded in the intermediate-risk (hazard ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p = 0.011) higher mortality, respectively, compared to low-risk patients at 16.6 years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally predictive of cardiovascular risk.In conclusion, a widely applicable rapid clinical algorithm using AHCPR criteria can reliably predict long-term mortality and cardiovascular outcomes. This algorithm, when applied in the ED, affords an excellent opportunity to identify patients who might benefit from a more aggressive cardiovascular risk factor management strategy.

  10. Feasibility of the AML profiler (Skyline™ Array) for patient risk stratification in a multicentre trial: a preliminary comparison with the conventional approach.

    PubMed

    Nomdedéu, Josep F; Puigdecanet, Eulalia; Bussaglia, Elena; Hernández, Juan José; Carricondo, Maite; Estivill, Camino; Martí-Tutusaus, Josep Maria; Tormo, Mar; Zamora, Lurdes; Serrano, Elena; Perea, Granada; de Llano, Maria Paz Queipo; García, Antoni; Sánchez-Ortega, Isabel; Ribera, Josep Maria; Nonell, Lara; Aventin, Anna; Solé, Francesc; Brunet, Maria Salut; Sierra, Jorge

    2016-05-03

    Deoxyribonucleic acid microarrays allow researchers to measure mRNA levels of thousands of genes in a single experiment and could be useful for diagnostic purposes in patients with acute myeloid leukaemia (AML). We assessed the feasibility of the AML profiler (Skyline™ Array) in genetic stratification of patients with de novo AML and compared the results with those obtained using the standard cytogenetic and molecular approach. Diagnostic bone marrow from 31 consecutive de novo AML cases was used to test MLL-PTD, FLT3-ITD and TKD, NPM1 and CEBPAdm mutations. Purified RNA was used to assess RUNX1-RUNX1T1, PML-RARα and CBFβ-MYH11 rearrangements. RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD-NPM1) and BAALC and EVI1 expression. Thirty cases were successfully analysed with both methods. Five cases had FLT3-ITD. In one case, a t(8;21) was correctly detected by both methods. Four cases had inv(16); in one, the RNA quality was unsatisfactory and it was not hybridized, and in the other three, the AML profiler detected the genetic lesion - this being a rare type I translocation in one case. Two cases with acute promyelocytic leukaemia were diagnosed by both methods. Results for NPM1 mutations were concordant in all but two cases (2/11, non-ABD mutations). Analysis of costs and turnaround times showed that the AML profiler was no more expensive than the conventional molecular approach. These results suggest that the AML profiler could be useful in multicentre trials to rapidly identify patients with AML with a good prognosis. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Analyzing nocturnal noise stratification.

    PubMed

    Rey Gozalo, Guillermo; Barrigón Morillas, Juan Miguel; Gómez Escobar, Valentín

    2014-05-01

    Pollution associated to traffic can be considered as one of the most relevant pollution sources in our cities; noise is one of the major components of traffic pollution; thus, efforts are necessary to search adequate noise assessment methods and low pollution city designs. Different methods have been proposed for the evaluation of noise in cities, including the categorization method, which is based on the functionality concept. Until now, this method has only been studied (with encouraging results) for short-term, diurnal measurements, but nocturnal noise presents a behavior clearly different on respect to the diurnal one. In this work 45 continuous measurements of approximately one week each in duration are statistically analyzed to identify differences between the proposed categories. The results show that the five proposed categories highlight the noise stratification of the studied city in each period of the day (day, evening, and night). A comparison of the continuous measurements with previous short-term measurements indicates that the latter can be a good approximation of the former in diurnal period, reducing the resource expenditure for noise evaluation. Annoyance estimated from the measured noise levels was compared with the response of population obtained from a questionnaire with good agreement. The categorization method can yield good information about the distribution of a pollutant associated to traffic in our cities in each period of the day and, therefore, is a powerful tool for town planning and the design of pollution prevention policies.

  12. Stratification Requirements for Seed Dormancy Alleviation in a Wetland Weed

    PubMed Central

    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

  13. 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.

  14. Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy

    PubMed Central

    Park, Inkeun; Choi, Seung Joon; Kim, Young Saing; Ahn, Hee Kyung; Hong, Junshik; Sym, Sun Jin; Park, Jinny; Cho, Eun Kyung; Lee, Jae Hoon; Shin, Yong Ju; Shin, Dong Bok

    2016-01-01

    Purpose The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed. Results A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials. PMID:27034148

  15. 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

  16. 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

  17. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: Noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease.

    PubMed

    Berman, Daniel S; Hachamovitch, Rory; Shaw, Leslee J; Friedman, John D; Hayes, Sean W; Thomson, Louise E J; Fieno, David S; Germano, Guido; Wong, Nathan D; Kang, Xingping; Rozanski, Alan

    2006-07-01

    This review deals with noninvasive imaging for risk stratification and with a conceptual approach to the selection of noninvasive tests in patients with suspected or known chronic coronary artery disease (CAD). Already widely acknowledged with SPECT, there is an increasing body of literature data demonstrating that CT coronary calcium assessment is also of prognostic value. The amount of coronary atherosclerosis, as can be extrapolated from CT coronary calcium score, has been shown to be highly predictive of cardiac events. The principal difference between myocardial perfusion SPECT (MPS) and CT coronary calcium for prognostic application appears to be that the former is an excellent tool for assessing short-term risk, thus effectively guiding decisions regarding revascularization. In contrast, the atherosclerosis imaging methods are likely to provide greater long-term risk assessment and, thus, are more useful in determination of the need for aggressive medical prevention measures. Although the more recent development of CT coronary angiography is promising for diagnosis, there has been no information to date regarding the prognostic value of the CT angiographic data. Similarly, cardiac MRI has not yet been adequately studied for its prognostic content. The selection of the most appropriate test for a given patient depends on the specific question being asked. In patients with a very low likelihood of CAD, no imaging test may be required. In screening the remaining asymptomatic patients, atherosclerosis imaging may be beneficial. In symptomatic patients, MPS, CT coronary angiography, and cardiac MRI play important roles. We consider it likely that, with an increased emphasis on prevention and a concomitant aging of the population, many forms of noninvasive cardiac imaging will continue to grow, with nuclear cardiology continuing to grow.

  18. Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium.

    PubMed

    Zeidan, A M; Al Ali, N; Barnard, J; Padron, E; Lancet, J E; Sekeres, M A; Steensma, D P; DeZern, A; Roboz, G; Jabbour, E; Garcia-Manero, G; List, A; Komrokji, R

    2017-02-24

    While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models. We identified 370 t-MDS patients (19%) among 1950 MDS patients. Prior therapy included chemotherapy alone (48%), chemoradiation (31%), and radiation alone in 21%. Median survival for t-MDS patients was significantly shorter than for d-MDS (19 vs 46 months, P<0.005). All models discriminated survival in t-MDS (P<0.005 for each model). Patients with t-MDS had a significantly higher hazard of death relative to d-MDS in every risk model, and had inferior survival compared to patients with d-MDS within all risk group categories. AIC Scores (lower is better) were 2316 (MPSS), 2343 (TPSS), 2343 (IPSS-R), 2361 (WPSS) and 2364 (IPSS). In conclusion, subsets of t-MDS patients with varying clinical outcomes can be identified using conventional risk stratification models. The MPSS, TPSS and IPSS-R provide the best predictive power.Leukemia advance online publication, 24 February 2017; doi:10.1038/leu.2017.33.

  19. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification.

    PubMed

    Wang, Yu; Wu, De-Pei; Liu, Qi-Fa; Qin, Ya-Zhen; Wang, Jing-Bo; Xu, Lan-Ping; Liu, Yan-Rong; Zhu, Hong-Hu; Chen, Jia; Dai, Min; Huang, Xiao-Jun

    2014-09-18

    We asked whether minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels could identify allogeneic hematopoietic stem cell transplantation (allo- HSCT) t(8;21) (q22;q22) acute myeloid leukemia patients who are at high risk for relapse, together with the impact of c-KIT mutations. Ninety-two consecutive adult t(8;21) patients who received allo-HSCT in complete remission were enrolled. MRD status at 1, 2, and 3 months after HSCT identified relapse patients (P5.05, P < .001, P5.0001, respectively). The 2-year cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) was 32% vs 9% (P 5 .01) and 55% vs 70% (P 5 .12) for patients with and without c-KIT mutations, respectively. In multivariate analysis, MRD at the first 3 months after HSCT, rather than c-KIT mutations,was an independent factor for CIR (P5.001) and LFS(P5.001). In addition, 17 patients received donor lymphocyte infusion (DLI) as interventional therapy for MRD, and the 2-year CIR and LFS for patients with or without DLI was 24% vs 87% (P5.001) and 64%vs 0%(P < .001), respectively. In conclusion, MRD monitoring early after transplant allows further rapid identification of t(8;21) patients at high risk of relapse and was more predictive of relapse risk than c-KIT mutations.

  20. The first Latin-American risk stratification system for cardiac surgery: can be used as a graphic pocket-card score.

    PubMed

    Carosella, Victorio C; Navia, Jose L; Al-Ruzzeh, Sharif; Grancelli, Hugo; Rodriguez, Walter; Cardenas, Cesar; Bilbao, Jorge; Nojek, Carlos

    2009-08-01

    This study aims to develop the first Latin-American risk model that can be used as a simple, pocket-card graphic score at bedside. The risk model was developed on 2903 patients who underwent cardiac surgery at the Spanish Hospital of Buenos Aires, Argentina, between June 1994 and December 1999. Internal validation was performed on 708 patients between January 2000 and June 2001 at the same center. External validation was performed on 1087 patients between February 2000 and January 2007 at three other centers in Argentina. In the development dataset the area under receiver operating characteristics (ROC) curve was 0.73 and the Hosmer-Lemeshow (HL) test was P=0.88. In the internal validation ROC curve was 0.77. In the external validation ROC curve was 0.81, but imperfect calibration was detected because the observed in-hospital mortality (3.96%) was significantly lower than the development dataset (8.20%) (P<0.0001). Recalibration was done in 2007, showing excellent level of agreement between the observed and predicted mortality rates on all patients (P=0.92). This is the first risk model for cardiac surgery developed in a population of Latin-America with both internal and external validation. A simple graphic pocket-card score allows an easy bedside application with acceptable statistic precision.

  1. Plasma Stratification by Planar Shocks

    NASA Astrophysics Data System (ADS)

    Keenan, Brett; Simakov, Andrei; Taitano, William; Chacon, Luis; Daughton, William

    2016-10-01

    A number of experimental observables in neutron yield and capsule compression in Inertial Confinement Fusion (ICF) experiments have been evading explanation by standard, single-fluid, hydrodynamic (hydro) numerical simulations. Fuel stratification - resulting from particle diffusion, multi-ion temperature separation (in the case of OMEGA experiments with gas filled capsules), and certain kinetic effects - is a likely culprit. As a preliminary step to elucidate these effects, we consider mass fraction and temperature stratification by shocks in plasmas with two ion species. We present an analytical solution valid for very weak shocks (M - 1 << 1). Employing the state-of-the-art Vlasov-Fokker-Planck code, iFP, we describe the stratification for shocks with arbitrary mach number, and we rigorously delineate the kinetic and hydrodynamic regimes in terms of Mach number, relative species concentration, and ion species mass ratio - thereby clarifying the conditions under which significant departure from single-fluid hydrodynamics may occur.

  2. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: a review of the current understanding of epidemiology, biology, risk stratification, and management of myeloma precursor disease.

    PubMed

    Agarwal, Amit; Ghobrial, Irene M

    2013-03-01

    The term monoclonal gammopathy of undetermined significance (MGUS) was coined in 1978. The recent advances in our knowledge about MGUS and smoldering multiple myeloma (SMM) have helped us better understand the pathogenesis of myeloma. It seems that myeloma evolves from a precursor state in almost all cases. We do not completely understand the multistep process from the precursor state to myeloma, but studies like whole genome sequencing continue to improve our understanding of this process. The process of transformation may not be linear acquisition of changes, but rather a branched heterogeneous process. Clinical features that are prognostic of rapid transformation have been identified, but no specific molecular markers have been identified. Even with recent advances, multiple myeloma remains an incurable disease in the vast majority, and intervening at the precursor state provides a unique opportunity to alter the natural history of the disease. A limitation is that a vast majority of patients with precursor disease, especially low-risk MGUS, will never progress to myeloma in their lifetime, and treating these patients is not only unnecessary but may be potentially harmful. The challenge is to identify a subset of patients with the precursor state that would definitely progress to myeloma and in whom interventions will have a meaningful impact. As our understanding of the molecular and genetic processes improves, these studies will guide the selection of high-risk patients more appropriately and ultimately direct a tailored management strategy to either delay progression to symptomatic myeloma or even "cure" a person at this premalignant stage.

  3. Monoclonal gammopathy of undetermined significance and Smoldering Multiple Myeloma: A review of the current understanding of epidemiology, biology, risk stratification and management of myeloma precursor disease

    PubMed Central

    Agarwal, Amit; Ghobrial, Irene

    2012-01-01

    The term monoclonal gammopathy of undetermined significance (MGUS) was coined in 1978. The recent advances in our knowledge about MGUS and smoldering MM (SMM) have helped us better understand the pathogenesis of myeloma. It appears that myeloma evolves from a precursor state in almost all cases. We do not completely understand the multistep process from the precursor state to myeloma but studies including whole genome sequencing will continue to help in improving our understanding of this process. The process of transformation may not be linear acquisition of changes but rather a branched heterogeneous process. Clinical features that are prognostic of rapid transformation have been identified but no specific molecular markers have been identified. Even with recent advances, multiple myeloma remains an incurable disease in the vast majority and intervening at the precursor state provides a unique opportunity to alter the natural history of the disease. A limitation is that a vast majority of patients with precursor disease especially low risk MGUS will never progress to myeloma in their lifetime and treating these patients is not only unnecessary but may be potentially harmful. The challenge is to identify a subset of patients with the precursor state that would definitely progress to myeloma and in whom interventions will have a meaningful impact. As our understanding of the molecular and genetic processes improves, these studies will guide the selection of high-risk patients more appropriately and ultimately direct a tailored management strategy to either delay progression to symptomatic myeloma or even “cure” a person at this premalignant stage. PMID:23224402

  4. Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis

    PubMed Central

    Honore, Patrick M.; Nguyen, H. Bryant; Gong, Michelle; Chawla, Lakhmir S.; Bagshaw, Sean M.; Artigas, Antonio; Shi, Jing; Joannes-Boyau, Olivier; Vincent, Jean-Louis

    2016-01-01

    -like growth factor-binding protein 7 was 0.84 (0.73–0.92) and 0.85 (0.76–0.94), in low and high nonrenal Sequential Organ Failure Assessment score subgroups. Performance of the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 test was not modified by nonrenal Sequential Organ Failure Assessment (p = 0.70). In multivariate analysis, the addition of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 significantly improved the performance of a clinical model for predicting acute kidney injury (p = 0.015). Conclusion: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 accurately predicts acute kidney injury in septic patients with or without other organ failures. PMID:27355527

  5. 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

  6. 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…

  7. Orderedness and Stratificational "and" Nodes.

    ERIC Educational Resources Information Center

    Herrick, Earl M.

    It is possible to apply Lamb's stratificational theory and analysis to English graphonomy, but additional notation devices must be used to explain particular graphemes and their characteristics. The author presents cases where Lamb's notation is inadequate. In those cases, he devises new means for performing the analysis. The result of this…

  8. Social Stratification and Education in Industrial Countries

    ERIC Educational Resources Information Center

    Bereday, George Z. F.

    1977-01-01

    Reviews the intersection of social stratification and schools, i.e., how stratification "shows up" in education. Assesses the responsibility and role of the school in creating a balance between the two forces. (Author/RK)

  9. Can the conventional sextant prostate biopsy accurately predict unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, Janice M; Mouraviev, Vladimir; Sun, Leon; Tsivian, Matvey; Madden, John F; Polascik, Thomas J

    2011-01-01

    We evaluate the reliability of routine sextant prostate biopsy to detect unilateral lesions. A total of 365 men with complete records including all clinical and pathologic variables who underwent a preoperative sextant biopsy and subsequent radical prostatectomy (RP) for clinically localized prostate cancer at our medical center between January 1996 and December 2006 were identified. When the sextant biopsy detects unilateral disease, according to RP results, the NPV is high (91%) with a low false negative rate (9%). However, the sextant biopsy has a PPV of 28% with a high false positive rate (72%). Therefore, a routine sextant prostate biopsy cannot provide reliable, accurate information about the unilaterality of tumor lesion(s).

  10. HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway.

    PubMed

    Budal, Elisabeth B; Haugland, Hans K; Skar, Robert; Maehle, Bjørn O; Bjørge, Tone; Vintermyr, Olav K

    2014-02-01

    In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005-2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3-6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34-50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone.

  11. Equine seroprevalence rates as an additional indicator for a more accurate risk assessment of the West Nile virus transmission.

    PubMed

    Vignjević, Goran; Vrućina, Ivana; Sestak, Ivana; Turić, Natasa; Bogojević, Mirta Sudarić; Merdić, Enrih

    2013-09-01

    The West Nile Virus (WNV) is a zoonotic arbovirus that has recently been causing outbreaks in many countries in southern and Central Europe. In 2012, for the first time, it caused an outbreak in eastern Croatia with total of 7 human clinical cases. With an aim of assisting public health personnel in order to improve survey protocols and vector control, the high risk areas of the WNV transmission were estimated and mapped. The study area included cities of Osijek and Slavonski Brod and 8 municipalities in Vukovarsko-Srijemska County. Risk estimation was based on seroprevalence of WNV infections in horses as an indicator of the virus presence, as well as the presence of possible WNV mosquito vectors with corresponding vector competences. Four mosquito species considered as possible WNV vectors are included in this study: Aedes vexans, Culex modestus, Culex pipiens and Ochlerotatus caspius. Mosquitoes were sampled using dry-ice baited CDC trap, twice a month, between May and October. This study suggests that the two mosquito species present the main risk of WNV transmission in eastern Croatia: the Culex pipiens--because of good vector competence and the Aedes vexans--because of the very high abundances. As a result, these two species should be focus of future mosquito surveillance and a vector control management.

  12. Ontological Stratification in an Ecology of Infohabitants

    NASA Astrophysics Data System (ADS)

    Abramov, V. A.; Goossenaerts, J. B. M.; de Wilde, P.; Correia, L.

    This paper reports progress from the EEII research project where ontological stratification is applied in the study of openness. We explain a stratification approach to reduce the overall complexity of conceptual models, and to enhance their modularity. A distinction is made between ontological and epistemological stratification. The application of the stratification approach to agent system design is explained and illustrated. A preliminary characterization of the relevant strata is given. The wider relevance of this result for information infrastructure design is addressed: ontological stratification will be key to the model management and semantic interoperability in a ubiquitous and model driven information infrastructure.

  13. 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

  14. 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.

  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. Interannual variability of upper ocean stratification in Bay of Bengal: observational and modeling aspects

    NASA Astrophysics Data System (ADS)

    Fousiya, T. S.; Parekh, Anant; Gnanaseelan, C.

    2016-10-01

    The annual cycle and interannual variability of stratification in Bay of Bengal (BoB) are studied using both observations and Global Ocean Data Assimilation System (GODAS) analysis during 2003-2012. Annual cycle of stratification and sea surface temperature (SST) evolve coherently, highlighting its role on modulating air-sea interaction over this climatologically important region. Spatial distribution of stratification shows strong seasonality in ARGO observations, whereas it is highly underestimated in GODAS with highest discrepancies during fall and spring. The annual cycle of sea surface salinity (SSS) in GODAS is out of phase with observations implying potential feedbacks. During La Niña years, SSS drop in fall and winter and are lesser than those reported during El Niño years. All these features are misrepresented in GODAS. As stratification modulates air-sea interaction over BoB especially during El Niño and La Niña years, such misrepresentation of ocean stratification may lead to unrealistic thermocline-SST coupling in the models. The mean stratification and its interannual variability in GODAS are weaker than observed even though interannual variability in freshwater flux (P-E) is higher in GODAS. Detailed analysis of GODAS with in situ observations reveals that upper ocean current shear (vertical) is overestimated in GODAS, leading to unrealistically strong mixing which is primarily responsible for the deeper penetration of surface warm and freshwater resulting weaker stratification. As GODAS is used to initialize the ocean component of the coupled forecasting system for seasonal prediction of Asian monsoon, proper representation of stratification is essential. This study advocates the need of accurate representation of upper ocean salinity in GODAS for improved stratification. We speculate that improved stratification and mixing in the BoB improve summer monsoon forecast.

  17. 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.

  18. 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.

  19. Applying optimal model selection in principal stratification for causal inference.

    PubMed

    Odondi, Lang'o; McNamee, Roseanne

    2013-05-20

    Noncompliance to treatment allocation is a key source of complication for causal inference. Efficacy estimation is likely to be compounded by the presence of noncompliance in both treatment arms of clinical trials where the intention-to-treat estimate provides a biased estimator for the true causal estimate even under homogeneous treatment effects assumption. Principal stratification method has been developed to address such posttreatment complications. The present work extends a principal stratification method that adjusts for noncompliance in two-treatment arms trials by developing model selection for covariates predicting compliance to treatment in each arm. We apply the method to analyse data from the Esprit study, which was conducted to ascertain whether unopposed oestrogen (hormone replacement therapy) reduced the risk of further cardiac events in postmenopausal women who survive a first myocardial infarction. We adjust for noncompliance in both treatment arms under a Bayesian framework to produce causal risk ratio estimates for each principal stratum. For mild values of a sensitivity parameter and using separate predictors of compliance in each arm, principal stratification results suggested that compliance with hormone replacement therapy only would reduce the risk for death and myocardial reinfarction by about 47% and 25%, respectively, whereas compliance with either treatment would reduce the risk for death by 13% and reinfarction by 60% among the most compliant. However, the results were sensitive to the user-defined sensitivity parameter.

  20. 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.

  1. Confidence-based stratification of CAD recommendations with application to breast cancer detection

    NASA Astrophysics Data System (ADS)

    Habas, Piotr A.; Zurada, Jacek M.; Elmaghraby, Adel S.; Tourassi, Georgia D.

    2006-03-01

    We present a risk stratification methodology for predictions made by computer-assisted detection (CAD) systems. For each positive CAD prediction, the proposed technique assigns an individualized confidence measure as a function of the actual CAD output, the case-specific uncertainty of the prediction estimated from the system's performance for similar cases and the value of the operating decision threshold. The study was performed using a mammographic database containing 1,337 regions of interest (ROIs) with known ground truth (681 with masses, 656 with normal parenchyma). Two types of decision models (1) a support vector machine (SVM) with a radial basis function kernel and (2) a back-propagation neural network (BPNN) were developed to detect masses based on 8 morphological features automatically extracted from each ROI. The study shows that as requirements on the minimum confidence value are being restricted, the positive predictive value (PPV) for qualifying cases steadily improves (from PPV = 0.73 to PPV = 0.97 for the SVM, from PPV = 0.67 to PPV = 0.95 for the BPNN). The proposed confidence metric was successfully applied for stratification of CAD recommendations into 3 categories of different expected reliability: HIGH (PPV = 0.90), LOW (PPV = 0.30) and MEDIUM (all remaining cases). Since radiologists often disregard accurate CAD cues, an individualized confidence measure should improve their ability to correctly process visual cues and thus reduce the interpretation error associated with the detection task. While keeping the clinically determined operating point satisfied, the proposed methodology draws the CAD users' attention to cases/regions of highest risk while helping them confidently eliminate cases with low risk.

  2. The Need for Accurate Risk Prediction Models for Road Mapping, Shared Decision Making and Care Planning for the Elderly with Advanced Chronic Kidney Disease.

    PubMed

    Stryckers, Marijke; Nagler, Evi V; Van Biesen, Wim

    2016-11-01

    As people age, chronic kidney disease becomes more common, but it rarely leads to end-stage kidney disease. When it does, the choice between dialysis and conservative care can be daunting, as much depends on life expectancy and personal expectations of medical care. Shared decision making implies adequately informing patients about their options, and facilitating deliberation of the available information, such that decisions are tailored to the individual's values and preferences. Accurate estimations of one's risk of progression to end-stage kidney disease and death with or without dialysis are essential for shared decision making to be effective. Formal risk prediction models can help, provided they are externally validated, well-calibrated and discriminative; include unambiguous and measureable variables; and come with readily applicable equations or scores. Reliable, externally validated risk prediction models for progression of chronic kidney disease to end-stage kidney disease or mortality in frail elderly with or without chronic kidney disease are scant. Within this paper, we discuss a number of promising models, highlighting both the strengths and limitations physicians should understand for using them judiciously, and emphasize the need for external validation over new development for further advancing the field.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Prognostic stratification in the treatment of AML.

    PubMed

    Asou, Norio

    Current treatment of acute myeloid leukemia (AML) still relies on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). AML is a heterogeneous neoplasm characterized by distinct chromosomal and genetic abnormalities. Recent comprehensive gene analyses have highlighted distinct genetic subgroups that are associated with different responses to chemotherapy. Therefore, the molecular landscape of AML is fundamental to the development of novel therapeutic approaches and provides opportunities for individualization of therapy. In addition, the age-related incidence of clonal hematopoiesis is high, affecting nearly 10% of healthy people more than 65 years of age. Clonal hematopoiesis is confirmed by the presence of mutations related to AML including genes involved in DNA methylation, chromatin modification and RNA splicing. In the analysis of gene mutation profiles in secondary AML (s-AML) from myelodysplastic syndromes and myeloproliferative neoplasms, secondary-type gene mutations were identified with >95% specificity in s-AML as compared with de novo AML, including RNA splicing, chromatin modification and cohesion complex genes, and were highly associated with poor responses to chemotherapy as well as TP53 mutation. It is important to identify genetic subgroups at relatively high-risk of relapses who should receive allogeneic HSCT during the first remission. In this review, prognostic stratification for individualized treatment of AML is discussed.

  8. Modeling surf zone-inner shelf exchange: Interaction of rip currents and stratification

    NASA Astrophysics Data System (ADS)

    Kumar, N.; Feddersen, F.

    2014-12-01

    Transient rip currents on alongshore uniform beaches develop from the coalescence of surf zone eddies, exchanging tracers between the surf zone and the potentially stratified inner shelf. The interaction of stratification and transient rip currents has not yet been investigated. Surf zone eddies responsible for transient rip currents are generated by short-crested wave breaking, a process included in wave-resolving (WR) Boussinesq models. However, WR models are depth-integrated and cannot account for stratification and vertically sheared flows. Wave-averaged (WA) models can simulate these processes, but cannot create surf zone eddies. A combination of WR and WA models is required to accurately simulate surf zone-inner shelf exchange. Here, WR depth-integrated Boussinessq model funwaveC is coupled to the stratification and depth-resolving WA Coupled-Ocean-Atmosphere-Wave-Sediment Transport (COAWST) modeling system. The surf zone eddy generation forcing is extracted from a funwaveC simulation of normally incident waves on a planar beach, and provided to COAWST as a depth-uniform surf zone force. COAWST model simulations resolving the surf zone to mid-shelf are conducted with surf zone eddy forcing, idealistic surface heating/cooling, stratification, and Coriolis effects. These simulations provide three-dimensional evolution of velocity and temperature, diagnosed to quantify the role of surf zone eddy forcing in surf zone-inner shelf exchange. The impact of stratification on rip currents and exchange is studied by varying the stratification. Funded by the Office of Naval Research.

  9. Clues toward precision medicine in oral squamous cell carcinoma: utility of next-generation sequencing for the prognostic stratification of high-risk patients harboring neck lymph node extracapsular extension

    PubMed Central

    Wang, Hung-Ming; Liao, Chun-Ta; Yen, Tzu-Chen; Chen, Shu-Jen; Lee, Li-Yu; Hsieh, Chia-Hsun; Lin, Chien-Yu; Ng, Shu-Hang

    2016-01-01

    Patients with resected oral squamous cell carcinoma (OSCC) harboring extracapsular extension (ECE) of the involved lymph node, show poor and heterogeneous outcomes. We aim to improve their prognostic stratification by combining genetic information from next-generation sequencing (NGS) using traditional clinicopathological prognosticators. The hotspot mutation regions of 45 cancer-related genes were investigated using NGS with an ultra-deep (>1000×) sequencing approach in formalin-fixed paraffin-embedded samples obtained from 201 patients with resected OSCC harboring ECE. Adjuvant chemoradiotherapy (CRT) and the number of nodes with ECE were the most important traditional prognosticators for disease-specific survival (DSS). The 5-year DSS for patients with CRT versus without, was 55% versus 21% (P < 0.001), and that for 1-3 versus ≥ 4 ECEs was 60% versus 25% (P = 0.001), respectively. Multivariate analysis in patients who received adjuvant CRT for 1-3 ECEs (i.e., those with a favorable expected prognosis) identified the following adverse prognostic factors: 1) margin of < 5 mm for locoregional failure (66% versus 30%, P = 0.007) and DSS (42% versus 63%, P = 0.039); 2) HRAS mutation for distant failure (55% versus 25%, P = 0.007) and DSS (36% versus 63%, P = 0.024); and 3) TP53 DNA-binding domain missense mutations for DSS (52% versus 71%, P = 0.025) and overall survival (39% versus 61%, P = 0.007). We conclude that genetic information from NGS may improve the prognostic stratification offered by traditional prognosticators in resected OSCC patients with ECE. Our findings will contribute to implementation of precision medicine in OSCC patients. PMID:27590518

  10. Stratification and mobility in contemporary Egypt.

    PubMed

    Nagi, Saad Z; Nagi, Omar

    2011-01-01

    The objectives in this statement are to characterize and explain the patterns of change in stratification and mobility in Egypt, over the last half century, by placing them within conceptual, explanatory, and historical contexts. First, literature relevant to the primary concepts of "class" and "status", is reviewed. Second, four institutions whose influence is fundamental in shaping these patterns are identified to form an explanatory context: family, polity, economy, and education. And third, an historical account is presented to demonstrate the interplay of these institutions and their consequences for stratification and mobility. For this, four periods are identified that are marked by change in the dominance of institutions and their corresponding influence on stratification and mobility. In addition to data available in relevant literature, this analysis utilizes primary data generated through a national probability household survey.

  11. A Critique of Duncan's Stratification Research.

    ERIC Educational Resources Information Center

    Crowder, N. David

    Duncan's interpretation of his research on the nature and process of the distribution of rewards in the U.S. stratification system is questioned. Statistical and conceptual flaws are noted in Duncan's work and their implications explored. A reanalysis of primary survey data is presented and, based on a reinterpretation of this data, a…

  12. Stratification dynamics in drying colloidal mixtures.

    PubMed

    Howard, Michael P; Nikoubashman, Arash; Panagiotopoulos, Athanassios Z

    2017-03-28

    Stratification in binary colloidal mixtures was investigated using implicit-solvent molecular dynamics simulations. For large particle size ratios and film Péclet numbers greater than unity, smaller colloids migrated to the top of the film, while big colloids were pushed to the bottom, creating an "inverted" stratification. This peculiar behavior was observed in recent simulations and experiments conducted by Fortini et al. (Phys. Rev. Lett. 2016, 116, 118301). To rationalize this behavior, particle size ratios and drying rates spanning qualitatively different Péclet number regimes were systematically studied, and the dynamics of the inverted stratification were quantified in detail. The stratified layer of small colloids was found to grow faster and to larger thicknesses for larger size ratios. Interestingly, inverted stratification was observed even at moderate drying rates where the film Péclet numbers were comparable to unity, but the thickness of the stratified layer decreased. A model based on dynamical density functional theory is proposed to explain the observed phenomena.

  13. Thermal stratification in liquid storage tanks

    NASA Technical Reports Server (NTRS)

    Christensen, D. L.; Han, S. M.

    1980-01-01

    Comprehensive literature survey indicates thermal stratification in solarenergy/liquid-storage tank improves system performance by as much as 15 percent. Collector efficiency increases when collector inlet fluid is drawn from bottom of storage tank, where fluid is coolest; warmest liquid drawn top of tank to satisfy thermal load.

  14. Stratification in Ap star atmospheres: Simulations

    NASA Astrophysics Data System (ADS)

    Cowley, Charles R.; Castelli, Fiorella

    2017-01-01

    It is now well established that the atmospheres of Ap stars can be chemically stratified (cf. Babel, A\\&A 258, 645, 1992; Ryabchikova et al. A\\&A 384, 545, 2002). The most convincing cases have been made with the profiles of very strong lines, such as Ca II K. Weaker line profiles are less obvious indicators. The collective behavior of sets or groups of lines have also been used. For example, if higher abundances are derived for strong lines in an atmosphere with zero microturbulence, one may assume that the absorbing species has been pushed into the higher photospheres. An example are the medium-strong Mn II lines in HgMn stars. In this paper, we probe this assumption by calculating line strengths with various assumed stratification models, and then determining abundances from those lines using an {\\bf unstratified} model with the same Teff and log(g). We use the model from Castelli, Kurucz \\& and Hubrig (A\\&A, 508, 401, 2009) for HR 6000, whose spectrum shows numerous indications of stratification. A variety of stratification models are considered, for example, ones where the majority of an absorbing species is concentrated above (or below) $log(\\tau_{5000}$ = -2.0. Cloud models are also investigated, where a species is concentrated within a range of photospheric depths. Curves of growth are generated in unstratified atmospheres for lines by holding the abundance fixed, and increasing log(gf). Similar curves are made in stratified models, and the ratios of strong to weak linesare compared with and without stratification. The effects of stratification on ionization are also investigated, as well as on the profiles of strong lines. We find, in agreement with previous work, that severe abundance jumps are sometimes required to account for some of the observed peculiarities.

  15. 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.)

  16. 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)....

  17. 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.

  18. Stratification of ALS patients' survival: a population-based study.

    PubMed

    Marin, Benoît; Couratier, Philippe; Arcuti, Simona; Copetti, Massimiliano; Fontana, Andrea; Nicol, Marie; Raymondeau, Marie; Logroscino, Giancarlo; Preux, Pierre Marie

    2016-01-01

    The natural history of amyotrophic lateral sclerosis (ALS) and patient risk stratification are areas of considerable research interest. We aimed (1) to describe the survival of a representative cohort of French ALS patients, and (2) to identify covariates associated with various patterns of survival using a risk classification analysis. ALS patients recruited in the FRALim register (2000-2013) were included. Time-to-death analyses were performed using Kaplan-Meier method and Cox model. A recursive partitioning and amalgamation (RECPAM) algorithm analysis identified subgroups of patients with different patterns of survival. Among 322 patients, median survival times were 26.2 and 15.6 months from time of onset and of diagnosis, respectively. Four groups of patients were identified, depending on their baseline characteristics and survival (1) ALSFRS-R slope >0.46/month and definite or probable ALS (median survival time (MST) 10.6 months); (2) ALSFRS-R slope >0.46/month and possible or probable laboratory-supported ALS (MST: 18.1 months); (3) ALSFRS-R slope ≤0.46/month and definite or probable ALS (MST: 22.5 months), and (4) ALSFRS-R slope ≤0.46/month and possible or probable laboratory-supported ALS (MST: 37.6 months). Median survival time is among the shortest ever reported by a worldwide population-based study. This is probably related to the age structure of the patients (the oldest identified to date), driven by the underlying population (30 % of subjects older than 60 years). Further research in the field of risk stratification could help physicians better anticipate prognosis of ALS patients, and help improve the design of randomized controlled trials.

  19. Deep circulations under simple classes of stratification

    NASA Technical Reports Server (NTRS)

    Salby, Murry L.

    1989-01-01

    Deep circulations where the motion field is vertically aligned over one or more scale heights are studied under barotropic and equivalent barotropic stratifications. The study uses two-dimensional equations reduced from the three-dimensional primitive equations in spherical geometry. A mapping is established between the full primitive equations and general shallow water behavior and the correspondence between variables describing deep atmospheric motion and those of shallow water behavior is established.

  20. 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.

  1. 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.

  2. [The role of biochemical markers of myocardial damage in clinical practice: the diagnosis of infarct and risk stratification. The Intersociety Interdisciplinary Study Group of the ANMCO-SIBioC-SIMeL, Markers of Muocardial Lesions. L'Associazione Nazionale Medici Cardiologi Ospedalieri-Società Italiana di Biochimica Clinica-Società Italiana di Medicina di Laboratorio].

    PubMed

    Ottani, F; Galvani, M; Panteghini, M; Dolci, A; Plebani, M; Tubaro, M; Zaninotto, M

    2000-01-01

    For many years creatine kinase (CK) and CK-MB isoenzymes were used together with the ECG to confirm the presence of myocardial infarction. During the last decade newer cardiac markers have been introduced and immunological test systems developed for their quantification. Among these new markers, a prominent role has emerged for cardiac troponins (T or I). These technological advanced assays have shown greater sensitivity compared to "conventional cardiac enzymes;, thereby identifying patients with small--at times, microscopic--infarcts who would not have met defining criteria for myocardial infarction in an earlier era. Another major advantage shown by both cardiac troponins with respect to "conventional cardiac enzymes" is their ability to predict clinical outcome over a short- or long-term follow-up in patients with acute coronary syndromes, and this appears to be particularly relevant in patients with micronecrosis, who constitute a high-risk subgroup of unstable angina patients. Recently, myoglobin has also been widely applied as a marker. Although lacking in myocardial specificity, it is the earliest marker to show an increase after coronary occlusion. Thus, the combined use of myoglobin and a cardiospecific structural protein such as troponin T or I may prove an attractive strategy for biochemical testing in chest pain patients. With the routine use of these novel cardiac markers, fascinating opportunities are now open in the field of diagnostic classification (making the World Health Organization definition of myocardial infarction obsolete) and risk stratification in chest pain patients; opportunities that were unforeseen in the era of cardiac enzymes. However, the use of these markers has also posed some important questions on: a) the best and most cost-effective diagnostic strategy in chest pain patients; b) the remaining role of cardiac enzymes; c) the therapeutic consequences of a positive test result.

  3. 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.

  4. An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

    PubMed Central

    Nixon, Iain J.; Wang, Laura Y.; Migliacci, Jocelyn C.; Eskander, Antoine; Campbell, Michael J.; Aniss, Ahmad; Morris, Lilah; Vaisman, Fernanda; Corbo, Rossana; Momesso, Denise; Vaisman, Mario; Carvalho, Andre; Learoyd, Diana; Leslie, William D.; Nason, Richard W.; Kuk, Deborah; Wreesmann, Volkert; Morris, Luc; Palmer, Frank L.; Ganly, Ian; Patel, Snehal G.; Singh, Bhuvanesh; Tuttle, R. Michael; Shaha, Ashok R.; Gönen, Mithat; Pathak, K. Alok; Shen, Wen T.; Sywak, Mark; Kowalski, Luis; Freeman, Jeremy; Perrier, Nancy; Shah, Jatin P.

    2016-01-01

    Background: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. Methods: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan–Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. Results: Using age 45 years as a cutoff, 10-year DSS rates for stage I–IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I–IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. Conclusions: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk. PMID:26914539

  5. Stratification of Landsat data by clustering

    NASA Technical Reports Server (NTRS)

    Bauer, M. E.; Davis, B. J.

    1976-01-01

    Full realization of the potential advantages of the synoptic coverage provided by Landsat will require the development and use of data analysis techniques which take into account the large variation and diversity of patterns found over many Landsat scenes. Stratification of the scene into units which are internally homogeneous is recommended as a first step in the analysis of data for whole or multiple frames of Landsat data. The use of clustering as an objective and efficient method of dividing scenes into areas which are spectrally similar (strata) is discussed and initial results, including classification performances and comparisons of spectral strata with major physical factors, are presented.

  6. Electrical stratification in the middle atmosphere

    NASA Technical Reports Server (NTRS)

    Croskey, C. L.; Hale, L. C.; Mitchell, J. D.

    1990-01-01

    Stratification of the electrical structure of the middle atmosphere (MA) has been observed under a wide range of conditions. 'Ledges' in charged particle density at the bottom of Chapman-like layers are accentuated in conductivity profiles due to the atmospheric density gradient's effect on mobility, but the steepest gradients yet observed occurred in conjunction with the horizontal magnetic field at the equator. High-latitude conductivity ledges are produced by steeply declining energy distributions. Measurements in a noctilucent cloud showed that the free electrons essentially vanished (presumably due to attachment to cloud particles) but the positive ion conductivity remained virtually unchanged.

  7. 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.

  8. Polarity and Stratification of the Epidermis

    PubMed Central

    Muroyama, Andrew; Lechler, Terry

    2012-01-01

    Polarity is a fundamental property of epithelial cells. In this review, we discuss our current knowledge of the polarity of a stratified epithelium, the epidermis, focusing on similarities and differences with simple epithelial models. We highlight how the differences in tissue architecture and physiology result in alterations in some aspects of cell polarity. In addition, we discuss one of the most prominent uses for cell polarity in the epidermis – orienting the mitotic spindle to drive the stratification and differentiation of this tissue during development. PMID:22960184

  9. 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.

  10. 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

  11. The influence of atmospheric stratification on scatterometer data

    NASA Technical Reports Server (NTRS)

    Louis, Jean-Francois; Hoffman, Ross N.

    1989-01-01

    The effects of atmospheric stratification and the stability of the atmospheric stratification on the scatterometer data measuring surface winds over the ocean were investigated using the boundary layer model developed by Louis (1979). A variational analysis method is proposed, which allows direct assimilation of scatterometer data. It is shown that the effect of the stability of atmospheric stratification on the wind increment is relatively small. However, it is a systematic effect, and neglecting it would consistently underestimate the winds in stable regions.

  12. Enrichment and stratification for predementia Alzheimer disease clinical trials.

    PubMed

    Holland, Dominic; McEvoy, Linda K; Desikan, Rahul S; Dale, Anders M

    2012-01-01

    The tau and amyloid pathobiological processes underlying Alzheimer disease (AD) progresses slowly over periods of decades before clinical manifestation as mild cognitive impairment (MCI), then more rapidly to dementia, and eventually to end-stage organ failure. The failure of clinical trials of candidate disease modifying therapies to slow disease progression in patients already diagnosed with early AD has led to increased interest in exploring the possibility of early intervention and prevention trials, targeting MCI and cognitively healthy (HC) populations. Here, we stratify MCI individuals based on cerebrospinal fluid (CSF) biomarkers and structural atrophy risk factors for the disease. We also stratify HC individuals into risk groups on the basis of CSF biomarkers for the two hallmark AD pathologies. Results show that the broad category of MCI can be decomposed into subsets of individuals with significantly different average regional atrophy rates. By thus selectively identifying individuals, combinations of these biomarkers and risk factors could enable significant reductions in sample size requirements for clinical trials of investigational AD-modifying therapies, and provide stratification mechanisms to more finely assess response to therapy. Power is sufficiently high that detecting efficacy in MCI cohorts should not be a limiting factor in AD therapeutics research. In contrast, we show that sample size estimates for clinical trials aimed at the preclinical stage of the disorder (HCs with evidence of AD pathology) are prohibitively large. Longer natural history studies are needed to inform design of trials aimed at the presymptomatic stage.

  13. Genetic testing in Tunisian families with heritable retinoblastoma using a low cost approach permits accurate risk prediction in relatives and reveals incomplete penetrance in adults.

    PubMed

    Ayari Jeridi, Hajer; Bouguila, Hédi; Ansperger-Rescher, Birgit; Baroudi, Olfa; Mdimegh, Imen; Omran, Ines; Charradi, Khaoula; Bouzayene, Hssan; Benammar-Elgaaïed, Amel; Lohmann, Dietmar R

    2014-07-01

    Heritable retinoblastoma is caused by oncogenic mutations in the RB1 tumor suppressor gene. Identification of these mutations in patients is important for genetic counseling and clinical management of relatives at risk. In order to lower analytical efforts, we designed a stepwise mutation detection strategy that was adapted to the spectrum of oncogenic RB1 gene mutations. We applied this strategy on 20 unrelated patients with familial and/or de novo bilateral retinoblastoma from Tunisia. In 19 (95%) patients, we detected oncogenic mutations including base substitutions, small length mutations, and large deletions. Further analyses on the origin of the mutations showed mutational mosaicism in one unilaterally affected father of a bilateral proband and incomplete penetrance in two mothers. In a large family with several retinoblastoma patients, the mutation identified in the index patient was also detected in several non-penetrant relatives. RNA analyses showed that this mutation results in an in-frame loss of exon 9. In summary, our strategy can serve as a model for RB1 mutation identification with high analytical sensitivity. Our results point out that genetic testing is needed to reveal or exclude incomplete penetrance specifically in parents of patients with sporadic disease.

  14. 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

  15. 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

  16. Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina.

    PubMed

    Matsuoka, Ryota L; Nguyen-Ba-Charvet, Kim T; Parray, Aijaz; Badea, Tudor C; Chédotal, Alain; Kolodkin, Alex L

    2011-02-10

    In the vertebrate retina, establishment of precise synaptic connections among distinct retinal neuron cell types is critical for processing visual information and for accurate visual perception. Retinal ganglion cells (RGCs), amacrine cells and bipolar cells establish stereotypic neurite arborization patterns to form functional neural circuits in the inner plexiform layer (IPL), a laminar region that is conventionally divided into five major parallel sublaminae. However, the molecular mechanisms governing distinct retinal subtype targeting to specific sublaminae within the IPL remain to be elucidated. Here we show that the transmembrane semaphorin Sema6A signals through its receptor PlexinA4 (PlexA4) to control lamina-specific neuronal stratification in the mouse retina. Expression analyses demonstrate that Sema6A and PlexA4 proteins are expressed in a complementary fashion in the developing retina: Sema6A in most ON sublaminae and PlexA4 in OFF sublaminae of the IPL. Mice with null mutations in PlexA4 or Sema6A exhibit severe defects in stereotypic lamina-specific neurite arborization of tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, intrinsically photosensitive RGCs (ipRGCs) and calbindin-positive cells in the IPL. Sema6A and PlexA4 genetically interact in vivo for the regulation of dopaminergic amacrine cell laminar targeting. Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes.

  17. Transmembrane semaphorin signaling controls laminar stratification in the mammalian retina

    PubMed Central

    Matsuoka, Ryota L.; Nguyen-Ba-Charvet, Kim T.; Parray, Aijaz; Badea, Tudor C.; Chédotal, Alain; Kolodkin, Alex L.

    2010-01-01

    In the vertebrate retina, establishment of precise synaptic connections among distinct retinal neuron cell types is critical for processing visual information and for accurate visual perception. Retinal ganglion cells (RGCs), amacrine cells, and bipolar cells establish stereotypic neurite arborization patterns to form functional neural circuits in the inner plexiform layer (IPL)1–3: a laminar region that is conventionally divided into five major parallel sublaminae1,2. However, the molecular mechanisms governing distinct retinal subtype targeting to specific sublaminae within the IPL remain to be elucidated. Here, we show that the transmembrane semaphorin Sema6A signals through its receptor PlexinA4 (PlexA4) to control lamina-specific neuronal stratification in the mouse retina. Expression analyses demonstrate that Sema6A and PlexA4 proteins are expressed in a complementary fashion in the developing retina: Sema6A in most ON sublaminae and PlexA4 in OFF sublaminae of the IPL. Mice with null mutations in PlexA4 or Sema6A exhibit severe defects in stereotypic lamina-specific neurite arborization of tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, intrinsically photosensitive RGCs (ipRGCs), and calbindin-positive cells in the IPL. Sema6A and PlexA4 genetically interact in vivo with respect to the regulation of dopaminergic amacrine cell laminar targeting. Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes. PMID:21270798

  18. Phosphorus fertilization, soil stratification and potential water quality impacts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water quality experts have suggested that no-till induces phosphorus stratification, which may exacerbate soluble P runoff from agricultural fields, leading to eutrophication. The objectives of this study were to explore P fertilization strategies on P stratification and P runoff from a corn-soybea...

  19. The Increasing Stratification of Higher Education: Ideology and Consequence

    ERIC Educational Resources Information Center

    Mayes, Sharon S.

    1977-01-01

    Institutions of higher education have rapidly expanded and, hence, diversified their social functions. Stratification of these institutions into elite universities, mass universities and community colleges replicates the class stratification in the work force. The relationships within this expansion and the resulting problems for the mass of…

  20. Racial Stratification and Education: The Case of Stockton, California.

    ERIC Educational Resources Information Center

    Ogbu, John U.

    This paper examines the educational consequences of racial stratification or the system of racial castes in the United States. The central thesis of the paper is that the subordinate status occupied by blacks because of racial stratification requires and promotes lower school performance or school failure and that therefore this school failure…

  1. 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.…

  2. 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…

  3. Using a Hypothetical Distribution of Grades to Introduce Social Stratification

    ERIC Educational Resources Information Center

    Brislen, William; Peoples, Clayton D.

    2005-01-01

    Teaching undergraduates about social stratification can be a difficult endeavor. As a number of authors have noted, undergraduate students are sometimes resistant to learning about social stratification, a phenomenon that may be due, in part, to the fact that many undergraduates are from privileged backgrounds and "find it difficult to go…

  4. Translated Poisson Mixture Model for Stratification Learning (PREPRINT)

    DTIC Science & Technology

    2007-09-01

    stratification learning in high dimensional data analysis in general and computer vision and image analysis in particular. 15. SUBJECT TERMS 16...unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Translated Poisson Mixture Model for Stratification Learning Gloria Haro Dept. Teoria ... general and computer vision and image analysis in particular. 1 Introduction Recently, there has been significant interest in analyzing the intrinsic

  5. Nonlinear Waves in Waveguides with Stratification.

    NASA Astrophysics Data System (ADS)

    Leble, Sergei B.

    S.B. Leble's book deals with nonlinear waves and their propagation in metallic and dielectric waveguides and media with stratification. The underlying nonlinear evolution equations (NEEs) are derived giving also their solutions for specific situations. The reader will find new elements to the traditional approach. Various dispersion and relaxation laws for different guides are considered as well as the explicit form of projection operators, NEEs, quasi-solitons and of Darboux transforms. Special points relate to: 1. the development of a universal asymptotic method of deriving NEEs for guide propagation; 2. applications to the cases of stratified liquids, gases, solids and plasmas with various nonlinearities and dispersion laws; 3. connections between the basic problem and soliton- like solutions of the corresponding NEEs; 4. discussion of details of simple solutions in higher- order nonsingular perturbation theory.

  6. Judgement post-stratification for designed experiments.

    PubMed

    Du, Juan; MacEachern, Steven N

    2008-06-01

    In many scientific studies, information that is not easily translated into covariates is ignored in the analysis. However, this type of information may significantly improve inference. In this research, we apply the idea of judgment post-stratification to utilize such information. Specifically, we consider experiments that are conducted under a completely randomized design. Sets of experimental units are formed, and the units in a set are ranked. Estimation is performed conditional on the sets and ranks. We propose a new estimator for a treatment contrast. We improve the new estimator by Rao-Blackwellization. Asymptotic distribution theory and corresponding inferential procedures for both estimators are developed. Simulation studies quantify the superiority of the new estimators and show their desirable properties for small and moderate sample sizes. The impact of the new techniques is illustrated with data from a clinical trial.

  7. 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.

  8. TEMPORARY REMOVAL: Channelopathies, genetic testing and risk stratification.

    PubMed

    Wilde, Arthur A M; Amin, Ahmad

    2017-03-18

    The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

  9. [Cardiovascular risk factors in women].

    PubMed

    Cengel, Atiye

    2010-03-01

    It is estimated that at least 80% of patients with cardiovascular disease (CVD) have conventional risk factors and optimization of these risk factors can reduce morbidity and mortality due to this disease considerably. Contemporary women have increased burden of some of these risk factors such as obesity, metabolic syndrome and smoking. Turkish women have a worse CV risk profile than Turkish men in some aspects. Risk stratification systems such as Framingham have a tendency of underestimating the risk in women. Coronary artery disease remains in vessel wall for a longer period of time in women; therefore obstructive disease appear later in their lifespan necessitating risk stratification systems for estimating their lifetime risk.

  10. Does preoperative cross-sectional imaging accurately predict main duct involvement in intraductal papillary mucinous neoplasm?

    PubMed

    Barron, M R; Roch, A M; Waters, J A; Parikh, J A; DeWitt, J M; Al-Haddad, M A; Ceppa, E P; House, M G; Zyromski, N J; Nakeeb, A; Pitt, H A; Schmidt, C Max

    2014-03-01

    Main pancreatic duct (MPD) involvement is a well-demonstrated risk factor for malignancy in intraductal papillary mucinous neoplasm (IPMN). Preoperative radiographic determination of IPMN type is heavily relied upon in oncologic risk stratification. We hypothesized that radiographic assessment of MPD involvement in IPMN is an accurate predictor of pathological MPD involvement. Data regarding all patients undergoing resection for IPMN at a single academic institution between 1992 and 2012 were gathered prospectively. Retrospective analysis of imaging and pathologic data was undertaken. Preoperative classification of IPMN type was based on cross-sectional imaging (MRI/magnetic resonance cholangiopancreatography (MRCP) and/or CT). Three hundred sixty-two patients underwent resection for IPMN. Of these, 334 had complete data for analysis. Of 164 suspected branch duct (BD) IPMN, 34 (20.7%) demonstrated MPD involvement on final pathology. Of 170 patients with suspicion of MPD involvement, 50 (29.4%) demonstrated no MPD involvement. Of 34 patients with suspected BD-IPMN who were found to have MPD involvement on pathology, 10 (29.4%) had invasive carcinoma. Alternatively, 2/50 (4%) of the patients with suspected MPD involvement who ultimately had isolated BD-IPMN demonstrated invasive carcinoma. Preoperative radiographic IPMN type did not correlate with final pathology in 25% of the patients. In addition, risk of invasive carcinoma correlates with pathologic presence of MPD involvement.

  11. Effect of self-stratification on sediment diffusivity in channel flows and boundary layers: a study using direct numerical simulations

    NASA Astrophysics Data System (ADS)

    Dutta, S.; Cantero, M. I.; Garcia, M. H.

    2014-08-01

    Sediment transport in nature comprises of bedload and suspended load, and precise modelling of these processes is essential for accurate sediment flux estimation. Traditionally, non-cohesive suspended sediment has been modelled using the advection-diffusion equation (Garcia, 2008), where the success of the model is largely dependent on accurate approximation of the sediment diffusion coefficients. The current study explores the effect of self-stratification on sediment diffusivity using suspended sediment concentration data from direct numerical simulations (DNS) of flows subjected to different levels of stratification, where the level of stratification is dependent on the particle size (parameterized using particle fall velocity Ṽ and volume-averaged sediment concentration (parameterized using shear Richardson number Riτ. Two distinct configurations were explored, first the channel flow configuration (similar to flow in a pipe or a duct) and second, a boundary-layer configuration (similar to open-channel flow). Self-stratification was found to modulate the turbulence intensity (Cantero et al., 2009b), which in turn was found to reduce vertical sediment diffusivity in portions of the domain exposed to turbulence damping. The effect of particle size on vertical sediment diffusivity has been studied in the past by several authors (Rouse, 1937; Coleman, 1970; Nielsen and Teakle, 2004); so in addition to the effect of particle size, the current study also explores the effect of sediment concentration on vertical sediment diffusivity. The results from the DNS simulations were compared with experiments (Ismail, 1952; Coleman, 1986) and field measurements (Coleman, 1970), and were found to agree qualitatively, especially for the case of channel flows. The aim of the study is to understand the effect of stratification due to suspended sediment on vertical sediment diffusivity for different flow configurations, in order to gain insight of the underlying physics, which

  12. Microwave remote sensing of natural stratification

    NASA Astrophysics Data System (ADS)

    Imperatore, Pasquale; Iodice, Antonio; Riccio, Daniele

    2011-11-01

    The response of natural stratification to electromagnetic wave has received much attention in last decades, due to its crucial role played in the remote sensing arena. In this context, when the superficial structure of the Earth, whose formation is inherently layered, is concerned, the most general scheme that can be adopted includes the characterization of layered random media. Moreover, a key issue in remote sensing of Earth and other Planets is to reveal the content under the surface illuminated by the sensors. For such a purpose, a quantitative mathematical analysis of wave propagation in three-dimensional layered rough media is fundamental in understanding intriguing scattering phenomena in such structures, especially in the perspective of remote sensing applications. Recently, a systematic formulation has been introduced to deal with the analysis of a layered structure with an arbitrary number of rough interfaces. Specifically, the results of the Boundary Perturbation Theory (BPT) lead to polarimetric, formally symmetric and physical revealing closed form analytical solutions. The comprehensive scattering model based on the BPT methodologically permits to analyze the bi-static scattering patterns of 3D multilayered rough media. The aim of this paper is to systematically show how polarimetric models obtainable in powerful BPT framework can be successfully applied to several situations of interest, emphasizing its wide relevance in the remote sensing applications scenario. In particular, a proper characterization of the relevant interfacial roughness is adopted resorting to the fractal geometry; numerical examples are then presented with reference to representative of several situations of interest.

  13. Stratification of women's sport in contemporary China.

    PubMed

    Xiong, Huan

    2011-01-01

    Since economic reform in the 1980s, Chinese sport has undergone an extraordinary transformation. The most distinguishing phenomenon is the rapid growth of mass sport at the grassroots level with increasing demands for physical activities in women's daily lives. The rapid growth of women's sports participation at the grassroots is deeply embedded in the process of social stratification as a result of the urbanisation of Chinese society. The purpose of this paper is to use the socialist, feminist and theoretical framework to explore how Chinese women's different economic, educational, domestic and cultural situations shape their sports values and patterns of participation, marking social boundaries in Chinese urban communities. Semi-structured interviews and observations were conducted with 60 female physical exercisers in sports clubs, parks and neighbourhood playgrounds. Documentary research was also applied as a complement method to the interview. The findings indicate that within different classes (middle class, working class and a group who were unemployed), many different opportunities for and limitations on women to participate in sport are noticed. Chinese women have not fully and equally utilised sports opportunities created by urbanisation. Most Chinese women still live within patriarchal arrangements. Consequently, they do not completely fulfil their ambitions in sport.

  14. Core merging and stratification following giant impact

    NASA Astrophysics Data System (ADS)

    Landeau, Maylis; Olson, Peter; Deguen, Renaud; Hirsh, Benjamin H.

    2016-10-01

    A stratified layer below the core-mantle boundary has long been suspected on the basis of geomagnetic and seismic observations. It has been suggested that the outermost core has a stratified layer about 100 km thick that could be due to the diffusion of light elements. Recent seismological evidence, however, supports a layer exceeding 300 km in thickness of enigmatic origin. Here we show from turbulent mixing experiments that merging between projectile and planetary core following a giant impact can lead to a stratified layer at the top of the core. Scaling relationships between post-impact core structure and projectile properties suggest that merging between Earth's protocore and a projectile core that is enriched in light elements and 20 times less massive can produce the thick stratification inferred from seismic data. Our experiments favour Moon-forming impact scenarios involving a projectile smaller than the proto-Earth and suggest that entrainment of mantle silicates into the protocore led to metal-silicate equilibration under extreme pressure-temperature conditions. We conclude that the thick stratified layer detected at the top of Earth's core can be explained as a vestige of the Moon-forming giant impact during the late stages of planetary accretion.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  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. 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.

  1. Accounting for Population Stratification in DNA Methylation Studies

    PubMed Central

    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.

    2014-01-01

    DNA methylation is an important epigenetic mechanism that has been linked to complex disease 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 (GWAS), 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 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 principal-components 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 SNP-based principal components, followed by methylation-based principal components, which out-perform both surrogate variable analysis and genomic control. Among our different approaches to computing methylation-based principal components, we find that principal components based on CpG sites chosen for their potential to proxy nearby SNPs can provide a powerful and computationally efficient approach to adjustment for population stratification in DNA methylation studies when genome-wide SNP data are unavailable. PMID:24478250

  2. Effects of viscosity and conductivity stratification on the linear stability and transient growth within compressible Couette flow

    NASA Astrophysics Data System (ADS)

    Saikia, Bijaylakshmi; Ramachandran, Ashwin; Sinha, Krishnendu; Govindarajan, Rama

    2017-02-01

    Accurate prediction of laminar to turbulent transition in compressible flows is a challenging task, as it can be affected by a combination of factors. Compressibility causes large variations in thermodynamic as well as transport properties of a gas, which in turn are known to affect flow stability. We study the stratification of individual transport properties and their combined behavior. We also examine the effect of a change in the magnitude of viscosity and conductivity on flow stability. The Couette flow of a perfect gas is our model problem and both modal and non-modal analyses are carried out. We notice a large destabilizing role of the increase in the conductivity value and a dramatic stabilizing effect of mean viscosity stratification, over a range of free-stream Mach number, Reynolds number, Prandtl number, and disturbance wavenumber. In the combined case, viscosity stratification plays a dominant role. We find this to be the case for finite-time transient growth in the parameter regime below linear instability as well as asymptotically at large time. A budget of the transient growth energy amplification is also shown to identify the effects of transport properties on the constituents of perturbation energy. The extensive results presented in this paper, we believe should motivate those studying more realistic flows to examine how these contrasting effects of stratification come together.

  3. 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

    2014-07-23

    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.

  4. Protein Changes during the Stratification of Malus domestica Borkh. Seed.

    PubMed

    Eichholtz, D A; Robitaille, H A; Herrmann, K M

    1983-07-01

    Apple seeds (Malus domestica Borkh. cv Golden Delicious) were stratified at 5 and 15 degrees C for various lengths, weighed, and soluble protein of axis and cotyledon tissue was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Only seeds treated at 5 degrees C germinated; seeds treated at 15 degrees C did not germinate. Optimal germination required 63 days of stratification. Excised embryos required less stratification time for germination than intact seeds. When stratification was less than 35 days, the resulting seedlings from 5 degrees C stratified embryos were dwarfed and epinastic. After 63 days of stratification, axes from 5 and 15 degrees C treated intact seeds had increased in fresh weight by 72 and 28% (w/w), respectively. The dry weights of the axes did not change significantly and both fresh and dry weights of cotyledons remained unchanged during stratification. Total soluble protein in axes and cotyledons changed very little during stratification. However, axis polypeptide profiles changed. Most obvious was the occurrence of a new polypeptide and the increase of four other clearly identifiable polypeptides during 5 degrees C treatment. The levels of the five most predominant axis proteins decreased at the same time. We observed no changes in the profiles of soluble cotyledon proteins. Control seeds kept at -10 degrees C showed none of the reported changes.

  5. Steady solutions for plumes in non-uniform stratifications

    NASA Astrophysics Data System (ADS)

    Kaye, Nigel; Scase, Matthew

    2010-11-01

    The plume conservation equations of Morton et al. (1956) are recast in terms of the plume radius, flux balance parameter γ, and a dimensionless parameter that characterizes the stratification. This set of equations lead to simple analytic solutions for steady straight sided plumes in non-uniformly stratified environments. Steady plumes in non-uniform stratification can occur for both stable (Caulfield & Woods 1998) and unstable (Batchelor 1954) stratifications whose strength has a power law variation with height. We present analytic solutions for the range of stratification power-law decay rates κ for which straight sided plumes are possible. The approach used provides significant physical insight into the limits on κ that permit straight sided solutions. We also present analytic solutions for the power law behaviour with height of the fluxes of volume, momentum and buoyancy. This result demonstrates that the models of Batchelor and Caulfield & Woods are two halves of the same continuum of solutions. The flux power law behavior explains the transition between the Batchelor solutions and the Caulfield & Woods solutions that occurs when κ=-8/3. For κ<-8/3 the buoyancy flux decays with height and, therefore, the stratification must be stable. Whereas for κ>-8/3 the buoyancy flux must increase with height, requiring an unstable stratification.

  6. Surgical mortality score: risk management tool for auditing surgical performance.

    PubMed

    Hadjianastassiou, Vassilis G; Tekkis, Paris P; Poloniecki, Jan D; Gavalas, Manolis C; Goldhill, David R

    2004-02-01

    Existing methods of risk adjustment in surgical audit are complex and costly. The present study aimed to develop a simple risk stratification score for mortality and a robust audit tool using the existing resources of the hospital Patient Administration System (PAS) database. This was an observational study for all patients undergoing surgical procedures over a two-year period, at a London university hospital. Logistic regression analysis was used to determine predictive factors of in-hospital mortality, the study outcome. Odds ratios were used as weights in the derivation of a simple risk-stratification model-the Surgical Mortality Score (SMS). Observed-to-expected mortality risk ratios were calculated for application of the SMS model in surgical audit. There were 11,089 eligible cases, under five surgical specialties (maxillofacial, orthopedic, renal transplant/dialysis, general, and neurosurgery). Incomplete data were 3.7% of the total, with no evidence of systematic underreporting. The SMS model was well calibrated [Hosmer-Lemeshow C-statistic: development set (3.432, p = 0.33), validation set (6.359, p = 0.10) with a high discriminant ability (ROC areas: development set [0.837, S.E.=0.013] validation set [0.816, S.E. = 0.016]). Subgroup analyses confirmed that the model can be used by the individual specialties for both elective and emergency cases. The SMS is an accurate risk- stratification model derived from existing database resources. It is simple to apply as a risk-management, screening tool to detect aberrations from expected surgical outcomes and to assist in surgical audit.

  7. Arrhythmic risk in congenital long QT syndrome.

    PubMed

    Kaufman, Elizabeth S

    2011-01-01

    One of the most important and challenging aspects of caring for patients with congenital long QT syndrome (LQTS) is assessing an individual's risk of sudden cardiac death (SCD) because of torsades de pointes. Current risk assessment integrates clinical and genetic features known to be associated with SCD, but more accurate methods of risk assessment could lead to more appropriate use of therapies, potentially saving lives and avoiding overtreatment. Conventional indices of risk include sex, age, extent of QT prolongation, history of symptoms (syncope or aborted SCD), and genetic subtype. The biophysical properties of specific mutations (eg, those that affect transmembrane segments of the ion channel protein or those that cause a dominant negative effect on ion channel function vs haplotype insufficiency) also contribute to risk. A growing body of basic mechanistic and clinical evidence points to heterogeneity of repolarization as a potent determinant of risk in LQTS patients. Mechanistically, heterogeneities of repolarization provide substrate for reentry, which likely causes perpetuation of torsades de pointes. Clinical markers that reflect heterogeneity of repolarization include abnormal microvolt-level T wave alternans, increased Tpeak-end interval, and dispersion of mechanical contraction time. The optimal methodology for using these indices as risk predictors in LQTS remains under active investigation. Further studies are needed to determine how indices of heterogeneity such as microvolt-level T wave alternans, Tpeak-end interval, and dispersion of mechanical contraction can be incorporated into models of risk prediction in LQTS, both for initial risk stratification and for assessment of efficacy of therapies.

  8. 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.

  9. 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

  10. Inclusion of hemoglobin level in prognostic score provides better prognostic stratification in patients with acute promyelocytic leukemia (APL).

    PubMed

    Park, Silvia; Lee, Su Jin; Kim, Kihyun; Jang, Jun Ho; Kim, Dong Hwan; Lee, Kyu Hyung; Lee, Je Hwan; Lee, Jung Hee; Kim, Dae Young; Jang, Dae-Young; Kim, Hawk; Park, Jae Hoo; Ryoo, Hun Mo; Bae, Sung Hwa; Kim, Min Kyung; Hyun, Myung Soo; Joo, Young Don; Lee, Won Sik; Lee, Sang Min; Jung, Chul Won

    2013-03-01

    The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥ 10 × 109/L, platelet <40 × 109/L, hemoglobin <8.0 g/dL) was considered as a risk factor; the sum of each was designated as the CBC-score. With a median follow-up of 8.4 years, the complete remission (CR) rate was 81.4 % (127/156), while 24 (15.4 %) were considered as treatment failures due to early death (ED). The 5-year overall survival (OS), leukemia-free survival, and cumulative incidence of relapse were 73.8, 82.8, and 13.5 %, respectively. Compared to the individual CBC parameters, combined prognostic systems such as PETHEMA or CBC-score provided better prognostic stratification. Compared to PETHEMA stratification, the proposed prognostic CBC-score system showed better stratification of APL patients in terms of CR rates (p = 0.004), OS (p = 0.004), and ED (p = 0.008). This retrospective study suggests that the proposed CBC-score may provide better prognostic stratification of APL patients.

  11. Stratification of Seismic Anisotropy Beneath Hudson Bay

    NASA Astrophysics Data System (ADS)

    Darbyshire, F. A.; Eaton, D. W.; Bastow, I. D.

    2012-12-01

    may represent a pervasive zone of metasomatism or underplating. Anisotropy patterns across the region also vary with depth, suggesting ~3 layers of stratification of lithospheric fabric. At the shallowest depths, anisotropic fast directions wrap around the Bay in a similar fashion to the patterns of isotropic wavespeed. The upper lithospheric mantle below is characterized by relatively weak and incoherent anisotropy; however the mid-to-lower lithosphere shows stronger anisotropy, with a pattern of fast directions broadly consistent with the tectonics of the Superior-Churchill collision as inferred from potential-field data. This may suggest some degree of coherency of deformation between the crust, uppermost mantle and lower lithosphere. These models of seismic wavespeed variation beneath the Hudson Bay region reveal the preservation of a major collision zone during the assembly of the Laurentian continental mass, and also suggest that the Archean cratons can be subdivided into different lithospheric domains that reflect their tectonic history but do not necessarily correspond to surface geological boundaries.

  12. BIOACCESSIBILITY TESTS ACCURATELY ESTIMATE ...

    EPA Pesticide Factsheets

    Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, we measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from five Pb-contaminated Superfund sites had relative bioavailabilities from 33%-63%, with a mean of about 50%. Treatment of two of the soils with P significantly reduced the bioavailability of Pb. The bioaccessibility of the Pb in the test soils was then measured in six in vitro tests and regressed on bioavailability. They were: the “Relative Bioavailability Leaching Procedure” (RBALP) at pH 1.5, the same test conducted at pH 2.5, the “Ohio State University In vitro Gastrointestinal” method (OSU IVG), the “Urban Soil Bioaccessible Lead Test”, the modified “Physiologically Based Extraction Test” and the “Waterfowl Physiologically Based Extraction Test.” All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the RBALP pH 2.5 and OSU IVG tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter 24%, or present as Pb sulfate 18%. Ad

  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.

  14. Regulation of mitotic spindle orientation during epidermal stratification.

    PubMed

    Xie, Wei; Zhou, Jun

    2016-12-20

    The epidermis is a stratified epithelium that serves as a barrier to infection from environmental pathogens and prevents water loss. Epidermal stratification is tightly controlled during embryogenesis. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance the growth of the skin surface area against the generation of differentiated cell layers. Therefore, understanding the relationship between oriented divisions of progenitor cells and the development and stratification of the epidermis is of paramount importance in the field of skin biology and pathology. We provide here an integrated view of recent studies implicating that improper orientation of the mitotic spindle contributes to disorders associated with abnormal epidermal stratification and suggesting that spindle orientation could serve as a potential therapeutic target in skin diseases.

  15. 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.

  16. Accurate spectral color measurements

    NASA Astrophysics Data System (ADS)

    Hiltunen, Jouni; Jaeaeskelaeinen, Timo; Parkkinen, Jussi P. S.

    1999-08-01

    Surface color measurement is of importance in a very wide range of industrial applications including paint, paper, printing, photography, textiles, plastics and so on. For a demanding color measurements spectral approach is often needed. One can measure a color spectrum with a spectrophotometer using calibrated standard samples as a reference. Because it is impossible to define absolute color values of a sample, we always work with approximations. The human eye can perceive color difference as small as 0.5 CIELAB units and thus distinguish millions of colors. This 0.5 unit difference should be a goal for the precise color measurements. This limit is not a problem if we only want to measure the color difference of two samples, but if we want to know in a same time exact color coordinate values accuracy problems arise. The values of two instruments can be astonishingly different. The accuracy of the instrument used in color measurement may depend on various errors such as photometric non-linearity, wavelength error, integrating sphere dark level error, integrating sphere error in both specular included and specular excluded modes. Thus the correction formulas should be used to get more accurate results. Another question is how many channels i.e. wavelengths we are using to measure a spectrum. It is obvious that the sampling interval should be short to get more precise results. Furthermore, the result we get is always compromise of measuring time, conditions and cost. Sometimes we have to use portable syste or the shape and the size of samples makes it impossible to use sensitive equipment. In this study a small set of calibrated color tiles measured with the Perkin Elmer Lamda 18 and the Minolta CM-2002 spectrophotometers are compared. In the paper we explain the typical error sources of spectral color measurements, and show which are the accuracy demands a good colorimeter should have.

  17. A Complete Piping Analysis With Thermal Stratification Loads

    SciTech Connect

    Milton Dong; Hong Ming Lee; Chii Chern

    2002-07-01

    The U. S. Nuclear Regulatory Commission (USNRC) had issued Bulletins 88-08, 88-11, 89-90, and 93-38 to address the concerns and problems due to thermal stratification loading during the life span of normal plant operation. The thermal stratification condition typically will cause pipe to bow in on a long horizontal segment. These conditions have not been commonly considered in piping design. However, the additional thermal cyclic stresses and loads due to these conditions could lead to the fatigue damage of the piping components and the failures of pipe supports. Analyzing the effects of thermal stratification loads can be very cumbersome if it is not a built-in functionality of the analysis program. Thus in response to the recent increase in such cases we have incorporated this feature in our piping stress computer program. A stress engineer can now define the thermal stratification conditions easily and the program will compute the pipe stresses and pipe support loads automatically as one of the load cases. The program then combines the thermal stratification load cases with other load cases as required in accordance with the load histogram to determine the cumulative fatigue damage of the piping system. The thermal cyclic stresses are evaluated in accordance with the design rules of Nuclear Class 1 piping components provided in NB-3650 of ASME section III Code. This paper presents the method, modeling and validation for implementing the functionality of analyzing thermal stratification loads in a computer program, as well as an application on an actual piping system as an illustration. (authors)

  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. Stratification approach for 3-D euclidean reconstruction of nonrigid objects from uncalibrated image sequences.

    PubMed

    Wang, Guanghui; Wu, Q M Jonathan

    2008-02-01

    This paper addresses the problem of 3-D reconstruction of nonrigid objects from uncalibrated image sequences. Under the assumption of affine camera and that the nonrigid object is composed of a rigid part and a deformation part, we propose a stratification approach to recover the structure of nonrigid objects by first reconstructing the structure in affine space and then upgrading it to the Euclidean space. The novelty and main features of the method lies in several aspects. First, we propose a deformation weight constraint to the problem and prove the invariability between the recovered structure and shape bases under this constraint. The constraint was not observed by previous studies. Second, we propose a constrained power factorization algorithm to recover the deformation structure in affine space. The algorithm overcomes some limitations of a previous singular-value-decomposition-based method. It can even work with missing data in the tracking matrix. Third, we propose to separate the rigid features from the deformation ones in 3-D affine space, which makes the detection more accurate and robust. The stratification matrix is estimated from the rigid features, which may relax the influence of large tracking errors in the deformation part. Extensive experiments on synthetic data and real sequences validate the proposed method and show improvements over existing solutions.

  20. Change in the Stratification of Educational Expectations and Their Realization

    ERIC Educational Resources Information Center

    Reynolds, John R.; Johnson, Monica Kirkpatrick

    2011-01-01

    What do recent trends toward increasingly ambitious educational expectations and rising college completion rates mean for the stratification of higher education? This article shows that the odds of achieving expectations for a bachelor's degree increased across 15 cohorts of young adults, and to a lesser extent, for expectations to attend…

  1. Introducing Social Stratification and Inequality: An Active Learning Technique.

    ERIC Educational Resources Information Center

    McCammon, Lucy

    1999-01-01

    Summarizes literature on techniques for teaching social stratification. Describes the three parts of an exercise that enables students to understand economic and political inequality: students are given a family scenario, create household budgets, and finally rework the national budget with their family scenario groups. Discusses student…

  2. Glacial ocean circulation and stratification explained by reduced atmospheric temperature.

    PubMed

    Jansen, Malte F

    2017-01-03

    Earth's climate has undergone dramatic shifts between glacial and interglacial time periods, with high-latitude temperature changes on the order of 5-10 °C. These climatic shifts have been associated with major rearrangements in the deep ocean circulation and stratification, which have likely played an important role in the observed atmospheric carbon dioxide swings by affecting the partitioning of carbon between the atmosphere and the ocean. The mechanisms by which the deep ocean circulation changed, however, are still unclear and represent a major challenge to our understanding of glacial climates. This study shows that various inferred changes in the deep ocean circulation and stratification between glacial and interglacial climates can be interpreted as a direct consequence of atmospheric temperature differences. Colder atmospheric temperatures lead to increased sea ice cover and formation rate around Antarctica. The associated enhanced brine rejection leads to a strongly increased deep ocean stratification, consistent with high abyssal salinities inferred for the last glacial maximum. The increased stratification goes together with a weakening and shoaling of the interhemispheric overturning circulation, again consistent with proxy evidence for the last glacial. The shallower interhemispheric overturning circulation makes room for slowly moving water of Antarctic origin, which explains the observed middepth radiocarbon age maximum and may play an important role in ocean carbon storage.

  3. Glacial ocean circulation and stratification explained by reduced atmospheric temperature

    NASA Astrophysics Data System (ADS)

    Jansen, Malte F.

    2017-01-01

    Earth’s climate has undergone dramatic shifts between glacial and interglacial time periods, with high-latitude temperature changes on the order of 5–10 °C. These climatic shifts have been associated with major rearrangements in the deep ocean circulation and stratification, which have likely played an important role in the observed atmospheric carbon dioxide swings by affecting the partitioning of carbon between the atmosphere and the ocean. The mechanisms by which the deep ocean circulation changed, however, are still unclear and represent a major challenge to our understanding of glacial climates. This study shows that various inferred changes in the deep ocean circulation and stratification between glacial and interglacial climates can be interpreted as a direct consequence of atmospheric temperature differences. Colder atmospheric temperatures lead to increased sea ice cover and formation rate around Antarctica. The associated enhanced brine rejection leads to a strongly increased deep ocean stratification, consistent with high abyssal salinities inferred for the last glacial maximum. The increased stratification goes together with a weakening and shoaling of the interhemispheric overturning circulation, again consistent with proxy evidence for the last glacial. The shallower interhemispheric overturning circulation makes room for slowly moving water of Antarctic origin, which explains the observed middepth radiocarbon age maximum and may play an important role in ocean carbon storage.

  4. The Social Stratification of the German VET System

    ERIC Educational Resources Information Center

    Protsch, Paula; Solga, Heike

    2016-01-01

    Germany is widely known for its vocational education and training (VET) system and its dual apprenticeship system in particular. What is often overlooked, however, is the vertical stratification within the German VET system. This is the focus of this study. Our analysis shows that the VET system, like the German school system, is highly…

  5. Pedagogic Stratification and the Shifting Landscape of Higher Education

    ERIC Educational Resources Information Center

    Stevenson, Jacqueline; Burke, Penny-Jane; Whelan, Pauline

    2014-01-01

    This project examined the impact on learning and teaching of recent significant changes in UK higher education policy. The term "pedagogic stratification" is used to explore and analyse how institutional type may relate to different conceptions of "teaching excellence" and "the student experience" adopted across the…

  6. 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.

  7. 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.…

  8. Examining the validity of the ACS-NSQIP Risk Calculator in plastic surgery: lack of input specificity, outcome variability and imprecise risk calculations.

    PubMed

    Johnson, Cassandra; Campwala, Insiyah; Gupta, Subhas

    2017-03-01

    American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) created the Surgical Risk Calculator, to allow physicians to offer patients a risk-adjusted 30-day surgical outcome prediction. This tool has not yet been validated in plastic surgery. A retrospective analysis of all plastic surgery-specific complications from a quality assurance database from September 2013 through July 2015 was performed. Patient preoperative risk factors were entered into the ACS Surgical Risk Calculator, and predicted outcomes were compared with actual morbidities. The difference in average predicted complication rate versus the actual rate of complication within this population was examined. Within the study population of patients with complications (n=104), the calculator accurately predicted an above average risk for 20.90% of serious complications. For surgical site infections, the average predicted risk for the study population was 3.30%; this prediction was proven only 24.39% accurate. The actual incidence of any complication within the 4924 patients treated in our plastic surgery practice from September 2013 through June 2015 was 1.89%. The most common plastic surgery complications include seroma, hematoma, dehiscence and flap-related complications. The ACS Risk Calculator does not present rates for these risks. While most frequent outcomes fall into general risk calculator categories, the difference in predicted versus actual complication rates indicates that this tool does not accurately predict outcomes in plastic surgery. The ACS Surgical Risk Calculator is not a valid tool for the field of plastic surgery without further research to develop accurate risk stratification tools.

  9. From bad to worse: collider stratification amplifies confounding bias in the "obesity paradox".

    PubMed

    Banack, Hailey R; Kaufman, Jay S

    2015-10-01

    Smoking is often identified as a confounder of the obesity-mortality relationship. Selection bias can amplify the magnitude of an existing confounding bias. The objective of the present report is to demonstrate how confounding bias due to cigarette smoking is increased in the presence of collider stratification bias using an empirical example and directed acyclic graphs. The empirical example uses data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of 15,792 men and women in the United States. Poisson regression models were used to examine the confounding effect of smoking. In the total ARIC study population, smoking produced a confounding bias of <3 percentage points. This result was obtained by comparing the incidence rate ratio (IRR) for obesity from a model adjusted for smoking was 1.07 (95 % CI 1.00, 1.15) with one that did not adjust for smoking was 1.10 (95 % CI 1.03, 1.18). However, among smokers with CVD, the obesity IRR was 0.89 (95 % CI 0.81, 0.99), while among non-smokers with CVD the obesity IRR was 1.20 (95 % CI 1.03, 1.41). The empirical and graphical explanations presented suggest that the magnitude of the confounding bias induced by smoking is greater in the presence of collider stratification bias.

  10. Effect of gravitational stratification on the propagation of a CME

    NASA Astrophysics Data System (ADS)

    Pagano, P.; Mackay, D. H.; Poedts, S.

    2013-12-01

    Context. Coronal mass ejections (CMEs) are the most violent phenomenon found on the Sun. One model that explains their occurrence is the flux rope ejection model. A magnetic flux rope is ejected from the solar corona and reaches the interplanetary space where it interacts with the pre-existing magnetic fields and plasma. Both gravity and the stratification of the corona affect the early evolution of the flux rope. Aims: Our aim is to study the role of gravitational stratification on the propagation of CMEs. In particular, we assess how it influences the speed and shape of CMEs and under what conditions the flux rope ejection becomes a CME or when it is quenched. Methods: We ran a set of MHD simulations that adopt an eruptive initial magnetic configuration that has already been shown to be suitable for a flux rope ejection. We varied the temperature of the backgroud corona and the intensity of the initial magnetic field to tune the gravitational stratification and the amount of ejected magnetic flux. We used an automatic technique to track the expansion and the propagation of the magnetic flux rope in the MHD simulations. From the analysis of the parameter space, we evaluate the role of gravitational stratification on the CME speed and expansion. Results: Our study shows that gravitational stratification plays a significant role in determining whether the flux rope ejection will turn into a full CME or whether the magnetic flux rope will stop in the corona. The CME speed is affected by the background corona where it travels faster when the corona is colder and when the initial magnetic field is more intense. The fastest CME we reproduce in our parameter space travels at ~850 km s-1. Moreover, the background gravitational stratification plays a role in the side expansion of the CME, and we find that when the background temperature is higher, the resulting shape of the CME is flattened more. Conclusions: Our study shows that although the initiation mechanisms of the

  11. Effect of self-stratification on sediment diffusivity in channel flows and boundary-layers: a study using Direct Numerical Simulations

    NASA Astrophysics Data System (ADS)

    Dutta, S.; Cantero, M. I.; Garcia, M. H.

    2013-11-01

    Sediment transport in nature comprises of bed-load and suspended load, and precise modelling of suspended load transport is essential for accurate sediment flux estimation. Traditionally, non-cohesive suspended sediment has been modelled using the advection-diffusion equation (Garcia, 2008), where the success of the model is largely dependent on accurate approximation of the sediment diffusion coefficients. The current study explores the effect of self-stratification on sediment diffusivity using suspended sediment concentration data from Direct Numerical Simulations (DNS) of flows subjected to different levels of stratification, where the level of stratification is dependent on the particle size (parameterized using particle fall velocity V~) and volume-averaged sediment concentration (parameterized using shear Richardson number Riτ). Two distinct configurations were explored, first the channel flow configuration (similar to flow in a pipe or a duct) and second, a boundary layer configuration (similar to open-channel flow). Self-stratification was found to modulate the turbulence intensity (Cantero et al., 2009), which in turn was found to reduce vertical sediment diffusivity in portions of the domain exposed to turbulence damping. Effect of particle size on vertical sediment diffusivity has been studied in the past by several authors (Rouse, 1937; Coleman, 1970; Nielsen and Teakle, 2004); so in addition to the effect of particle size, the current study also explores the effect of sediment concentration on vertical sediment diffusivity. The results from the DNS simulations were compared with experiments (Ismail, 1952; Coleman, 1986) and field measurements (Coleman, 1970); and were found to agree qualitatively especially for the case of channel flows. The aim of the study was to understand the effect of stratification due to suspended sediment on vertical sediment diffusivity

  12. "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.

  13. 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

  14. Transient development of stratification in a partially divided enclosure

    NASA Astrophysics Data System (ADS)

    Otis, D. R.; Jones, G. F.

    In passive solar heating of buildings or in compartment fires, we are concerned with the development of thermal stratification when two rooms at different temperatures are connected by the opening of a door. We have performed experiments and numerical calculations aimed at this application. The experiments consist of flow visualization and temperature measurements obtained when isolated halves of a tank containing water at two different temperatures are suddenly connected to allow flow between the zones. Two significant findings from this work are: (1) the presence of internal waves excited by the onset of flow through the doorway which have not normally been observed in past laboratory experiments, and (2) the equilibration time is found to be in general agreement with that predicted by a formula from a simple orifice model that we describe. Work is progressing on numerical simulations using two core stratification models connected by an orifice including entrainment in the neighborhood of the connection.

  15. 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

  16. 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.

  17. Upper Ocean Stratification in the Bay of Bengal

    DTIC Science & Technology

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Upper Ocean Stratification in the Bay of Bengal Eric A...oceanographers in the methods used. OBJECTIVES Upper ocean physics plays a key role in controlling the intensity and timing of the Northern Indian Ocean ...monsoons, with the ocean and atmosphere representing a strongly coupled air-sea interaction system, which in turn plays an important role in climate

  18. Risk

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel

    2016-01-01

    Speaking up, i.e. expressing ones concerns, is a critical piece of effective communication. Yet, we see many situations in which crew members have concerns and still remain silent. Why would that be the case? And how can we assess the risks of speaking up vs. the risks of keeping silent? And once we do make up our minds to speak up, how should we go about it? Our workshop aims to answer these questions, and to provide us all with practical tools for effective risk assessment and effective speaking-up strategies..

  19. Thermal stratification potential in rocket engine coolant channels

    NASA Technical Reports Server (NTRS)

    Kacynski, Kenneth J.

    1992-01-01

    The potential for rocket engine coolant channel flow stratification was computationally studied. A conjugate, 3-D, conduction/advection analysis code (SINDA/FLUINT) was used. Core fluid temperatures were predicted to vary by over 360 K across the coolant channel, at the throat section, indicating that the conventional assumption of a fully mixed fluid may be extremely inaccurate. Because of the thermal stratification of the fluid, the walls exposed to the rocket engine exhaust gases will be hotter than an assumption of full mixing would imply. In this analysis, wall temperatures were 160 K hotter in the turbulent mixing case than in the full mixing case. The discrepancy between the full mixing and turbulent mixing analyses increased with increasing heat transfer. Both analysis methods predicted identical channel resistances at the coolant inlet, but in the stratified analysis the thermal resistance was negligible. The implications are significant. Neglect of thermal stratification could lead to underpredictions in nozzle wall temperatures. Even worse, testing at subscale conditions may be inadequate for modeling conditions that would exist in a full scale engine.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Microfluidic destabilization of viscous stratifications: Interfacial waves and droplets

    NASA Astrophysics Data System (ADS)

    Hu, Xiaoyi; Cubaud, Thomas

    2016-11-01

    Microfluidic two-fluid flows with large differences in viscosity are experimentally investigated to examine the role of fluid properties on hydrodynamic destabilization processes at the small scale. Two- and three-layer flow configurations are systematically studied in straight square microchannels using miscible and immiscible fluid pairs. We focus our attention on symmetric three-layer stratifications with a fast central stream made of low-viscosity fluid and a slow sheath flow composed of high-viscosity fluid. We quantify the influence of the capillary and the Reynolds numbers on the formation and evolution of droplets and wavy stratifications. Several functional relationships are developed for the morphology and dynamics of droplets and interfacial waves including size, celerity and frequency. In the wavy stratification regime, the formation and entrainment of thin viscous ligaments from wave crests display a rich variety of dynamics either in the presence or in the absence of interfacial tension between liquids. This work is supported by NSF (CBET-1150389).

  5. 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.

  6. The benefits of designing a stratification system for New York City pediatric intensive care units for use in regional surge capacity planning and management.

    PubMed

    Campbell, Christiana

    2010-08-01

    Accurate assessment of New York City (NYC) pediatric intensive care unit (PICU) resources and the ability to surge them during a disaster has been recognized as an important citywide emergency preparedness activity. However, while NYC hospitals with PICUs may be expected to surge in a disaster, few of them have detailed surge capacity plans. This will likely make it difficult for them to realize their full surge capacity both on individual and regional levels. If the pediatric resources that each NYC PICU hospital has can be identified prior to a disaster, this information can be used to both determine appropriate surge capacity goals for each PICU hospital and the additional resources needed to reach those goals. City agencies can then focus citywide planning efforts on making these resources available and more easily anticipate what a hospital will need during a disaster. Communication of this hospital information both prior to and during a surge situation will be aided by a stratification system familiar to both city planners and hospitals. The goal of this project was to design a NYC PICU surge stratification system that would aid physicians, hospitals and city agencies in regional surge capacity planning for critical pediatric patients. This goal was demonstrated through two objectives. The first identified major factors to consider when designing a stratification system. The second devised a preliminary system of PICU stratification based on clinical criteria and resources.

  7. Systematically enhanced subarctic Pacific stratification and nutrient utilization during glacials

    NASA Astrophysics Data System (ADS)

    Knudson, K. P.; Ravelo, A. C.

    2015-12-01

    The modern subarctic North Pacific is characterized as a high-nitrate, low-chlorophyll (HNLC) area, but evidence for increased nutrient utilization during the last glacial indicates that this region is highly dynamic. As such, this HNLC area is of particular interest in regard to understanding changes in the biological pump and carbon sequestration and predicting how biogeochemical processes will influence, or be influenced by, future climate change. While it has been suggested that changes in iron supply and/or ocean stratification could explain fluctuations in nutrient utilization and productivity in the subarctic Pacific, short records of nutrient utilization have previously hindered the evaluation of these potential mechanisms over long timescales. Here we present new, high-resolution records of bulk sediment δ15N from 0-1.2 Ma from Integrated Ocean Drilling Program Exp. 323 Site U1342, which are used to calculate Δδ15N (U1342 δ15Nbulk - ODP Site 1012 δ15Nbulk) as a nitrate utilization proxy. The unprecedented length and resolution of this new record allows us, for the first time, to determine orbital-scale systematic behavior in subarctic Pacific nutrient utilization over many glacial/interglacial cycles. Spectral analyses demonstrate that enhanced nutrient utilization was paced by climate on Milankovitch orbital cycles since the Mid-Pleistocene Transition (MPT; ~800 ka). Nitrate utilization maxima is statistically correlated with glacial maxima and enhanced dust/iron availability (represented by existing records of EPICA ice core dust, Southern Pacific Ocean sediment iron, and China loess) but shows low correlation to primary productivity, suggesting that stratification has systematically exerted an important control on subarctic Pacific nutrient utilization since the MPT. These findings imply that the presence of iron helped to change the region into a nitrate-limited, rather than iron-limited, region during glacials and that stratification, which

  8. 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.

  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. 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

  11. Accurate Evaluation of Quantum Integrals

    NASA Technical Reports Server (NTRS)

    Galant, D. C.; Goorvitch, D.; Witteborn, Fred C. (Technical Monitor)

    1995-01-01

    Combining an appropriate finite difference method with Richardson's extrapolation results in a simple, highly accurate numerical method for solving a Schrodinger'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.

  12. Stratification at the Earth's largest hyperacidic lake and its consequences

    NASA Astrophysics Data System (ADS)

    Caudron, Corentin; Campion, Robin; Rouwet, Dmitri; Lecocq, Thomas; Capaccioni, Bruno; Syahbana, Devy; Suparjan; Purwanto, Bambang Heri; Bernard, Alain

    2017-02-01

    Volcanic lakes provide windows into the interior of volcanoes as they integrate the heat flux discharged by a magma body and condense volcanic gases. Volcanic lake temperatures and geochemical compositions therefore typically serve as warnings for resumed unrest or prior to eruptions. If acidic and hot, these lakes are usually considered to be too convective to allow any stratification within their waters. Kawah Ijen volcano, featuring the largest hyperacidic lake on Earth (volume of 27 million m3), is less homogeneous than previously thought. Hourly temperature measurements reveal the development of a stagnant layer of cold waters (<30 °C), overlying warmer and denser water (generally above 30 °C and density ∼1.083 kg/m3). Examination of 20 yrs of historical records and temporary measurements show a systematic thermal stratification during rainy seasons. The yearly rupture of stratification at the end of the rainy season causes a sudden release of dissolved gases below the cold water layer which appears to generate a lake overturn, i.e. limnic eruption, and a resonance of the lake, i.e. a seiche, highlighting a new hazard for these extreme reservoirs. A minor non-volcanic event, such as a heavy rainfall or an earthquake, may act as a trigger. The density driven overturn requires specific salinity-temperature conditions for the colder and less saline top water layer to sink into the hot saline water. Spectacular degassing occurs when the dissolved gases, progressively stored during the rainy season due to a weakened diffusion of carbon dioxide in the top layer, are suddenly released. These findings challenge the homogenization assumption at acidic lakes and stress the need to develop appropriate monitoring setups.

  13. 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.

  14. 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.

  15. Horizontal flow stratification modifications for RELAP5/MOD3

    SciTech Connect

    Riemke, R.A.

    1989-02-01

    The report documents the modifications to the horizontal stratification model in RELAP5/MOD3. Background information, model description and solution method, coding changes, and assessment of these changes are described in the report. The use of the phasic velocity difference in the Taitel-Dukler criterion along with a mass flux criterion improved the void fraction data comparison for the TPTF tests. Modifications and error corrections to the void gradient term improved the code's capability to calculate the correct velocities. 15 refs., 23 figs., 1 tab.

  16. Stratification effects and IUE spectra of high excitation planetaries

    NASA Technical Reports Server (NTRS)

    Feibelman, W.; Aller, L. H.

    1982-01-01

    Individual strips across IUE low resolution images of a number of high excitation planetaries with appreciable angular disks (including NGC 2452, 3242, 6818, and IC 1297) are analyzed to assess stratification effects. The familiar enhancement of high excitation lines toward the center is well exhibited, but some unexpected structural features are found in NGC 2452 where C IV shows a single central maximum, but C III, Ne IV, and He II seem to have a central dip. The new IUE data permit improved chemical composition estimates for several planetaries previously analyzed by Aller and Czyzak.

  17. Evidence for Gropun-Water Stratification Near Yucca Mountain, Nevada

    SciTech Connect

    K. Futa; B.D. Marshall; Z.E. Peterman

    2006-03-24

    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.

  18. Risk/MRD adapted GMALL trials in adult ALL.

    PubMed

    Gökbuget, N; Raff, R; Brügge-Mann, M; Flohr, T; Scheuring, U; Pfeifer, H; Bartram, C R; Kneba, M; Hoelzer, D

    2004-01-01

    The German Multicenter Study Group for Adult ALL (GMALL) conducts since 1984 trials with risk adapted study design. The model of conventional prognostic factors comprises now WBC, age, immunophenotype, cytogenetics and molecular genetics. Risk stratification according to these factors allows a highly significant prediction of relapse risk in adult ALL. In the recent GMALL study minimal residual disease (MRD) was added to the risk model. Trials in childhood and adult ALL showed convincingly that MRD is a relevant and independent prognostic factor. It is of particular value in standard risk (SR) patients as defined by conventional factors. In the current GMALL study a risk stratification according to conventional factors is followed by a MRD based stratification in SR patients. Whereas high and very high risk patients receive a stem cell transplantation (SCT) in first CR after induction and first consolidation, SR patients receive cyclic consolidation therapy for one year with MRD monitoring. At the end of the first year a stratification according to course and level of MRD takes place. Treatment is stopped in patients with low risk whereas in high risk patients a SCT is planned. Patients who cannot be allocated to either group are treated as intermediate risk and receive one year of intensified maintenance therapy. Preliminary results show that MRD based risk stratification is feasible and that the treatment recommendations for MRD based risk groups are reasonable. In the future however an earlier identification of high risk patients (after 4 months) will be attempted.

  19. Morphometry and average temperature affect lake stratification responses to climate change

    NASA Astrophysics Data System (ADS)

    Kraemer, Benjamin M.; Anneville, Orlane; Chandra, Sudeep; Dix, Margaret; Kuusisto, Esko; Livingstone, David M.; Rimmer, Alon; Schladow, S. Geoffrey; Silow, Eugene; Sitoki, Lewis M.; Tamatamah, Rashid; Vadeboncoeur, Yvonne; McIntyre, Peter B.

    2015-06-01

    Climate change is affecting lake stratification with consequences for water quality and the benefits that lakes provide to society. Here we use long-term temperature data (1970-2010) from 26 lakes around the world to show that climate change has altered lake stratification globally and that the magnitudes of lake stratification changes are primarily controlled by lake morphometry (mean depth, surface area, and volume) and mean lake temperature. Deep lakes and lakes with high average temperatures have experienced the largest changes in lake stratification even though their surface temperatures tend to be warming more slowly. These results confirm that the nonlinear relationship between water density and water temperature and the strong dependence of lake stratification on lake morphometry makes lake temperature trends relatively poor predictors of lake stratification trends.

  20. 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.

  1. Biomarkers for cardiovascular risk assessment in autoimmune diseases.

    PubMed

    Teixeira, Priscila Camillo; Ferber, Philippe; Vuilleumier, Nicolas; Cutler, Paul

    2015-02-01

    Autoimmune diseases, such as antiphospholipid syndrome, systemic lupus erythematosus, and rheumatoid arthritis, are characterized by a high prevalence of cardiovascular (CV) disease (CVD), which constitutes the leading causes of morbidity and mortality among such patients. Although such effects are partly explained by a higher prevalence of traditional CV risk factors, many studies indicate that such factors do not fully explain the enhanced CV risk in these patients. In addition, risk stratification algorithms based upon traditional CV risk factors are not as predictive in autoimmune diseases as in the general population. For these reasons, the timely and accurate assessment of CV risk in these high-risk populations still remains an unmet clinical need. An enhanced contribution of different inflammatory components of the immune response, as well as autoimmune elements (e.g. autoantibodies, autoantigens, and cellular response), has been proposed to underlie the incremental CV risk observed in these populations. Recent advances in proteomic tools have contributed to the discovery of proteins involved in CVDs, including some that may be suitable to be used as biological markers. In this review we summarize the main markers in the field of CVDs associated with autoimmunity, as well as the recent advances in proteomic technology and their application for biomarker discovery in autoimmune disease.

  2. 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.

  3. Continental Shelf Embayments of the Eastern Margin of the Philippines; Lamon Bay Stratification & Circulation

    DTIC Science & Technology

    2012-09-30

    in 2011. Data from R/V Revelle hull mounted ADCP. The hull ADCP and the CTD thermohaline stratification reveal a shift in circulation pattern...Philippines; Lamon Bay Stratification & Circulation Arnold L. Gordon Lamont-Doherty Earth Observatory 61 Route 9W Palisades, NY 10964-8000... circulation , stratification and the Shelf-Slope interaction, and the resultant ocean productivity, within a major embayment, Lamon Bay, of the eastern

  4. Examining population stratification via individual ancestry estimates versus self-reported race.

    PubMed

    Barnholtz-Sloan, Jill S; Chakraborty, Ranajit; Sellers, Thomas A; Schwartz, Ann G

    2005-06-01

    Population stratification has the potential to affect the results of genetic marker studies. Estimating individual ancestry provides a continuous measure to assess population structure in case-control studies of complex disease, instead of using self-reported racial groups. We estimate individual ancestry using the Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci using two different analysis methods in a case-control study of early-onset lung cancer. Individual ancestry proportions were estimated for "European" and "West African" groups using published allele frequencies. The majority of Caucasian, non-Hispanics had >50% European ancestry, whereas the majority of African Americans had <20% European ancestry, regardless of ancestry estimation method, although significant overlap by self-reported race and ancestry also existed. When we further investigated the effect of ancestry and self-reported race on the frequency of a lung cancer risk genotype, we found that the frequency of the GSTM1 null genotype varies by individual European ancestry and case-control status within self-reported race (particularly for African Americans). Genetic risk models showed that adjusting for individual European ancestry provided a better fit to the data compared with the model with no group adjustment or adjustment for self-reported race. This study suggests that significant population substructure differences exist that self-reported race alone does not capture and that individual ancestry may be confounded with disease status and/or a candidate gene risk genotype.

  5. Correlation of population parameters leading to power differences in association studies with population stratification.

    PubMed

    He, Y; Jiang, R; Fu, W; Bergen, A W; Swan, G E; Jin, L

    2008-11-01

    The power of statistical tests to measure effect sizes in the presence of population stratification is an important issue for the design and analysis of population-based association studies. Comparisons of statistical tests have shown that the power of different statistical approaches varies in different genetic scenarios. However, the impact of stratified population parameters on statistical power is not yet understood in a general statistical framework, particularly the impact of correlated population parameters. To investigate such impact in detail, we implemented a genetic model for population-based association studies with stratified samples and evaluated the impact on power with different genetic scenarios. The investigation shows that correlation between disease prevalence and risk allele frequency among subpopulations impacts statistical power. In a model with five subpopulations and moderate population divergence (Fst= 0.01), the correlation accounts for more than 85% of power difference. Our results also show that the estimation of genetic effect for candidate loci is biased by population divergence. Beneficial alleles could be wrongly characterized as risk alleles when prevalence differences and divergences of risk loci are large among subpopulations.

  6. 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.

  7. [Epidemiological stratification of malaria in the Comoro archipelago].

    PubMed

    Blanchy, S; Julvez, J; Mouchet, J

    1999-07-01

    In the Comoros Islands, the level of malarial endemicity varies greatly from one island to the other, even though the total area (4 islands) covers less than 2,300 km2 and has a population of some 600,000 people only. The epidemiological stratification is based on the diversity of human and physical characterisation. They both determine the presence and the behaviour as well as the size of the vector's populations. Vectorial dynamics can explain varying levels of endemicity given parasitological indicators and specific morbidity. Analyzing these criteria shows up different epidemiological features and serves as a basic guideline for malaria control. The efficiency of this control depends on the relationships between the intensity and the length of the transmission, in the framework of protection mechanisms; it is of crucial importance for clinical treatment. Further elements are the age of the patient, the season and the geographic situation of the area. Stratification provides explanations for these relationships and helps to define antimalarial programmes adapting to each situation a range of therapeutic and antivectorial methods. The availability and accessibility of anti-malarial medicine is the minimum requirement for reducing mortality: domestic spray insecticides for reducing transmission are effective for several years and should be followed by the use of mosquito nets or curtains impregnated with pyrethrinoids, and in the particular case of Grande Comore, the use of larvivorous fish. As anywhere else, the economic development, which is dependent on political stability, is the essential basis for malaria control.

  8. Rumen content stratification in the giraffe (Giraffa camelopardalis).

    PubMed

    Sauer, Cathrine; Clauss, Marcus; Bertelsen, Mads F; Weisbjerg, Martin R; Lund, Peter

    2017-01-01

    Ruminants differ in the degree of rumen content stratification, with 'cattle-types' (i.e., the grazing and intermediate feeding ruminants) having stratified content, whereas 'moose-types' (i.e., the browsing ruminants) have unstratified content. The feeding ecology, as well as the digestive morphophysiology of the giraffe (Giraffa camelopardalis), suggest that it is a 'moose-type' ruminant. Correspondingly, the giraffe should have an unstratified rumen content and an even rumen papillation pattern. Digesta samples were collected from along the digestive tract of 27 wild-caught giraffes kept in bomas for up to 2months, and 10 giraffes kept in zoological gardens throughout their lives. Samples were analysed for concentration of dry matter, fibre fractions, volatile fatty acids and NH3, as well as mean particle size and pH. There was no difference between the dorsal and ventral rumen region in any of these parameters, indicating homogenous rumen content in the giraffes. In addition to the digesta samples, samples of dorsal rumen, ventral rumen and atrium ruminis mucosa were collected and the papillary surface enlargement factor was determined, as a proxy for content stratification. The even rumen papillation pattern observed also supported the concept of an unstratified rumen content in giraffes. Zoo giraffes had a slightly more uneven papillation pattern than boma giraffes. This finding could not be matched by differences in physical characteristics of the rumen content, probably due to an influence of fasting time ante mortem on these parameters.

  9. Mathematical Modelling of Thermal Stratification in a Cryogenic Propellant Tank

    NASA Astrophysics Data System (ADS)

    Agrawal, Gagan; Joseph, Jeswin; Agarwal, Deepak; Pisharady, J. C.; Kumar, S. Sunil

    2017-02-01

    Cryogenic tanks used for space applications are filled with sub-cooled cryogenic propellants, whose liquid-vapor interface remains undisturbed for long periods of time prior to launch. During this period, substantial amount of heat leaks into the tank from external sources such as solar and ambient convective fluxes, even though the tank is well insulated. This results in thermal stratification near the liquid vapour interface. A transient, two-phase, thermodynamic model of stratification in a cryogenic tank is developed, considering propellant boundary layer flow due to natural convection close to tank wall. Continuity, momentum, energy and mass transfer equations are solved using finite difference-based formulations of SINDA/FLUINT simulator. The analytical model is validated with test results reported in literature. Subsequently, studies are carried out to investigate the effect of liquid sub-cooling in propellant tank on stratified mass and liquid temperature profile. The study shows that sub-cooling of cryogenic tank leads to significant increase in stratified mass.

  10. MULTIGENERATIONAL ASPECTS OF SOCIAL STRATIFICATION: ISSUES FOR FURTHER RESEARCH

    PubMed Central

    Mare, Robert D.

    2014-01-01

    The articles in this special issue show the vitality and progress of research on multigenerational aspects of social mobility, stratification, and inequality. The effects of the characteristics and behavior of grandparents and other kin on the statuses, resources, and positions of their descendants are best viewed in a demographic context. Intergenerational effects work through both the intergenerational associations of socioeconomic characteristics and also differential fertility and mortality. A combined socioeconomic and demographic framework informs a research agenda which addresses the following issues: how generational effects combine with variation in age, period, and cohort within each generation; distinguishing causal relationships across generations from statistical associations; how multigenerational effects vary across socioeconomic hierarchies, including the possibility of stronger effects at the extreme top and bottom; distinguishing between endowments and investments in intergenerational effects; multigenerational effects on associated demographic behaviors and outcomes (especially fertility and mortality); optimal tradeoffs among diverse types of data on multigenerational processes; and the variability across time and place in how kin, education, and other institutions affect stratification. PMID:24748709

  11. Tim-3 is highly expressed in T cells in acute myeloid leukemia and associated with clinicopathological prognostic stratification.

    PubMed

    Li, Caixia; Chen, Xiaochen; Yu, Xiao; Zhu, Yibei; Ma, Chao; Xia, Rui; Ma, Jinfeng; Gu, Caihong; Ye, Lu; Wu, Depei

    2014-01-01

    T cells immunoglobulin mucin 3 (Tim-3) is an important inhibitory stimulatory molecule, which has been reported to play a vital role in the tumor immune escape and be correlated with clinicopathological prognostic stratification in solid tumor. However, the related research is rare of Tim-3 in non-solid tumor, such as acute myeloid leukemia (AML). In this study, we investigated the expression characteristics of Tim-3 on the peripheral blood T cells of newly diagnosed AML patients and its clinical significance. Peripheral blood was obtained from 36 patients with newly diagnosed AML before intervention, with peripheral blood from 20 cases of healthy volunteers collected as normal control. Expression levels of Tim-3 on the peripheral blood T cells were assayed with flow cytometry. We found that Tim-3 expression on the peripheral blood CD4+ T cells and CD8+ T cells in newly diagnosed AML patients were significantly increased compared with that of normal control. CD4+ T cells/CD8+ T cell ratio (CD4/CD8) of peripheral blood in AML patients was significantly correlated with NCCN high risk group. The higher expression level of Tim-3 on CD4+ T cells in the peripheral blood of AML patients had significant correlation with FLT3-ITD mutation, the higher expression level of Tim-3 on CD8+ T cells in AML patients was significantly correlated with NCCN high risk group. To conclude, our results support the concept that Tim-3 is highly expressed on the peripheral blood T cells of AML patients, and Tim-3 expression significantly correlates with clinicopathological prognostic stratification in AMLTim-3, T cell, acute myeloid leukemia, tumor immune escape, clinicopathological prognostic stratification.

  12. 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

  13. Robust dynamic myocardial perfusion CT deconvolution for accurate residue function estimation via adaptive-weighted tensor total variation regularization: a preclinical study

    NASA Astrophysics Data System (ADS)

    Zeng, Dong; Gong, Changfei; Bian, Zhaoying; Huang, Jing; Zhang, Xinyu; Zhang, Hua; Lu, Lijun; Niu, Shanzhou; Zhang, Zhang; Liang, Zhengrong; Feng, Qianjin; Chen, Wufan; Ma, Jianhua

    2016-11-01

    Dynamic myocardial perfusion computed tomography (MPCT) is a promising technique for quick diagnosis and risk stratification of coronary artery disease. However, one major drawback of dynamic MPCT imaging is the heavy radiation dose to patients due to its dynamic image acquisition protocol. In this work, to address this issue, we present a robust dynamic MPCT deconvolution algorithm via adaptive-weighted tensor total variation (AwTTV) regularization for accurate residue function estimation with low-mA s data acquisitions. For simplicity, the presented method is termed ‘MPD-AwTTV’. More specifically, the gains of the AwTTV regularization over the original tensor total variation regularization are from the anisotropic edge property of the sequential MPCT images. To minimize the associative objective function we propose an efficient iterative optimization strategy with fast convergence rate in the framework of an iterative shrinkage/thresholding algorithm. We validate and evaluate the presented algorithm using both digital XCAT phantom and preclinical porcine data. The preliminary experimental results have demonstrated that the presented MPD-AwTTV deconvolution algorithm can achieve remarkable gains in noise-induced artifact suppression, edge detail preservation, and accurate flow-scaled residue function and MPHM estimation as compared with the other existing deconvolution algorithms in digital phantom studies, and similar gains can be obtained in the porcine data experiment.

  14. 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

  15. The Role of Thermal Stratification in Modeling Biosphere-Atmosphere Scalar Fluxes

    NASA Astrophysics Data System (ADS)

    Juang, J.; Katul, G.; Siqueira, M.

    2002-05-01

    The state-of-the-art biosphere-atmosphere models used to compute heat, water vapor, and CO2 fluxes from canopies do not explicitly resolve local atmospheric stability. However, efforts to measure and model nighttime CO2 fluxes from ecosystems suggest that local atmospheric stability within the deeper canopy layers may be crucial towards accurate representation of nighttime CO2 fluxes. In order to assess the relative importance of atmospheric stability, a comprehensive micrometeorological model is developed to compute vertical profiles of the kinematic turbulent fluxes of momentum, heat, and moisture within and above a forest canopy. This model is based on coupling higher-order closure approximations with a biophysical description of scalar sources and sinks but retaining the density stratification terms in the scalar budget terms. Both second-order and third-order closure approximations are developed and compared. The measured fluxes in a Pinus taeda stand at Duke Forest are used to assess the model performance. To further investigate the relative effects of atmospheric stability on scalar concentration and source-sink distribution within the canopy volume, a set of simulations are conducted in which atmospheric stability effects are considered and neglected. The results focus on the interplay between leaf area density variation and incident radiation that promote large local atmospheric stability effects within the canopy volume.

  16. Stratification and loading of fecal indicator bacteria (FIB) in a tidally muted urban salt marsh.

    PubMed

    Johnston, Karina K; Dorsey, John H; Saez, Jose A

    2015-03-01

    Stratification and loading of fecal indicator bacteria (FIB) were assessed in the main tidal channel of the Ballona Wetlands, an urban salt marsh receiving muted tidal flows, to (1) determine FIB concentration versus loading within the water column at differing tidal flows, (2) identify associations of FIB with other water quality parameters, and (3) compare wetland FIB concentrations to the adjacent estuary. Sampling was conducted four times during spring-tide events; samples were analyzed for FIB and turbidity (NTU) four times over a tidal cycle at pre-allocated depths, depending on the water level. Additional water quality parameters measured included temperature, salinity, oxygen, and pH. Loadings were calculated by integrating the stratified FIB concentrations with water column cross-sectional volumes corresponding to each depth. Enterococci and Escherichia coli were stratified both by concentration and loading, although these variables portrayed different patterns over a tidal cycle. Greatest concentrations occurred in surface to mid-strata levels, during flood tides when contaminated water flowed in from the estuary, and during ebb flows when sediments were suspended. Loading was greatest during flood flows and diminished during low tide periods. FIB concentrations within the estuary often were significantly greater than those within the wetland tide channel, supporting previous studies that the wetlands act as a sink for FIB. For public health water quality monitoring, these results indicate that more accurate estimates of FIB concentrations would be obtained by sampling a number of points within a water column rather than relying only on single surface samples.

  17. Transient forcing effects on mixing of two fluids for a stable stratification

    NASA Astrophysics Data System (ADS)

    Pool, María.; Dentz, Marco; Post, Vincent E. A.

    2016-09-01

    Mixing and dispersion in coastal aquifers are strongly influenced by periodic temporal flow fluctuations on multiple time scales ranging from days (tides), seasons (pumping and recharge) to glacial cycles (regression and transgressions). Transient forcing effects lead to a complex space and time-dependent flow response which induces enhanced spreading and mixing of dissolved substances. We study effective mixing and solute transport in temporally fluctuating one-dimensional flow for a stable stratification of two fluids of different density using detailed numerical simulation as well as accurate column experiments. We quantify the observed transport behaviors and interface evolution by a time-averaged model that is obtained from a two-scale expansion of the full transport problem, and derive explicit expressions for the center of mass and width of the mixing zone between the two fluids. We find that the magnitude of transient-driven mixing is mainly controlled by the hydraulic diffusivity, the period, and the initial interface location. At an initial time regime, mixing can be characterized by an effective dispersion coefficient and both the interface position and width evolve linearly in time. At larger times, the spatial variability of the flow velocity leads to a deceleration of the interface and a compression of its width, which is manifested by a subdiffusive evolution of its width as t1/2.

  18. Creating Gender Equality: Cross-National Gender Stratification and Mathematical Performance.

    ERIC Educational Resources Information Center

    Baker, David P.; Jones, Deborah Perkins

    1993-01-01

    Reports on a study of eighth-grade mathematical performance of 77,000 students in 19 countries, data from 1964 and 1982 studies in 9 countries, and data on gender stratification and its impact on mathematics performance. Finds that a cross-national variation exists and that it is related to gender stratification. (CFR)

  19. Generating Social Stratification: Toward a New Research Agenda. Social Inequality Series.

    ERIC Educational Resources Information Center

    Kerckhoff, Alan C., Ed.

    Some leading students of social stratification in the United States present empirical and theoretical essays about the institutional contexts that shape careers. These 15 essays work toward the goal of identifying and assessing the processes by which a birth cohort is distributed in the stratification system, given its position of origin in that…

  20. 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…

  1. The Impact of Targeted School Vouchers on Racial Stratification in Louisiana Schools

    ERIC Educational Resources Information Center

    Egalite, Anna J.; Mills, Jonathan N.; Wolf, Patrick J.

    2017-01-01

    The question of how school choice programs affect the racial stratification of schools is highly salient in the field of education policy. We use a student-level panel data set to analyze the impacts of the Louisiana Scholarship Program (LSP) on racial stratification in public and private schools. This targeted school voucher program provides…

  2. Investigation of exit-velocity stratification effects on jets in a crossflow (STRJET)

    NASA Technical Reports Server (NTRS)

    Ziegler, H.

    1974-01-01

    Program determines flow field about jets with velocity stratification exhausting into crossflow. Jets with three different types of exit-velocity stratification have been considered: (a) jets with relatively high-velocity core, (b) jets with relatively low-velocity core, and (c) jets originating from vaned nozzle.

  3. "That's Not Fair!": A Simulation Exercise in Social Stratification and Structural Inequality

    ERIC Educational Resources Information Center

    Coghlan, Catherine L.; Huggins, Denise W.

    2004-01-01

    Social stratification may be one of the most difficult topics covered in sociology classes. This article describes an interactive learning exercise, using a modified version of the game Monopoly, intended to stress the structural nature of social inequality and to stimulate student reflection and class discussion on social stratification in the…

  4. Incorporation of Content Balancing Requirements in Stratification Designs for Computerized Adaptive Testing.

    ERIC Educational Resources Information Center

    Leung, Chi-Keung; Chang, Hua-Hua; Hau, Kit-Tai

    2003-01-01

    Studied three stratification designs for computerized adaptive testing in conjunction with three well-developed content balancing methods. Simulation study results show substantial differences in item overlap rate and pool utilization among different methods. Recommends an optimal combination of stratification design and content balancing method.…

  5. 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)

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Stratification in the lunar regolith - A preliminary view

    NASA Technical Reports Server (NTRS)

    Duke, M. B.; Nagle, J. S.

    1975-01-01

    Although our knowledge of lunar regolith stratification is incomplete, several categories of thick and thin strata have been identified. Relatively thick units average 2 to 3 cm in thickness, and appear surficially to be massive. On more detailed examination, these units can be uniformly fine-grained, can show internal trends, or can show internal variations which apparently are random. Other thick units contain soil clasts apparently reworked from underlying units. Thin laminae average approximately 1 mm in thickness; lenticular distribution and composition of some thin laminae indicates that they are fillets shed from adjacent rock fragments. Other dark fine-grained well-sorted thin laminae appear to be surficial zones reworked by micrometeorites. Interpretations of stratigraphic succession can be strengthened by the occurrence of characteristic coarse rock fragments and the orientation of large spatter agglutinates, which are commonly found in their original depositional orientation.

  13. 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.

  14. Positroid stratification of orthogonal Grassmannian and ABJM amplitudes

    NASA Astrophysics Data System (ADS)

    Kim, Joonho; Lee, Sangmin

    2014-09-01

    A novel understanding of scattering amplitudes in terms of on-shell diagrams and positive Grassmannian has been recently established for four dimensional Yang-Mills theories and three dimensional Chern-Simons theories of ABJM type. We give a detailed construction of the positroid stratification of orthogonal Grassmannian relevant for ABJM amplitudes. On-shell diagrams are classified by pairing of external particles. We introduce a combinatorial aid called `OG tableaux' and map each equivalence class of on-shell diagrams to a unique tableau. The on-shell diagrams related to each other through BCFW bridging are naturally grouped by the OG tableaux. Introducing suitably ordered BCFW bridges and positive coordinates, we construct the complete coordinate charts to cover the entire positive orthogonal Grassmannian for arbitrary number of external particles. The graded counting of OG tableaux suggests that the positive orthogonal Grassmannian constitutes a combinatorial polytope.

  15. Development of Retinal Amacrine Cells and Their Dendritic Stratification

    PubMed Central

    Balasubramanian, Revathi

    2014-01-01

    Themammalian retina containsmultiple neurons, each of which contributes differentially to visual processing. Of these retinal neurons, amacrine cells have recently come to prime light since they facilitate majority of visual processing that takes place in the retina. Amacrine cells are also the most diverse group of neurons in the retina, classified majorly based on the neurotransmitter type they express and morphology of their dendritic arbors. Currently, little is known about the molecular basis contributing to this diversity during development. Amacrine cells also contribute to most of the synapses in the inner plexiform layer and mediate visual information input from bipolar cells onto retinal ganglion cells. In this review, we will describe the current understanding of amacrine cell and cell subtype development. Furthermore, we will address the molecular basis of retinal lamination at the inner plexiform layer. Overall, our review will provide a developmental perspective of amacrine cell subtype classification and their dendritic stratification. PMID:25170430

  16. Experimental verification of scaling parameters for thermal stratification

    NASA Technical Reports Server (NTRS)

    Ji, H.-C.; Schwartz, S. H.; Lovrich, T. N.; Hochstein, J. I.; Holmes, L. A.

    1992-01-01

    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.

  17. Consensus and stratification in the affective meaning of human sociality.

    PubMed

    Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

    2014-06-03

    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.

  18. 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

  19. Career on the Move: Geography, Stratification, and Scientific Impact

    NASA Astrophysics Data System (ADS)

    Deville, Pierre; Wang, Dashun; Sinatra, Roberta; Song, Chaoming; Blondel, Vincent D.; Barabási, Albert-László

    2014-04-01

    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.

  20. Temperature, stratification and barnacle larval settlement in two Californian sites

    NASA Astrophysics Data System (ADS)

    Pineda, Jesús; López, Manuel

    2002-05-01

    Barnacle s ettlement was monitored in two sites 100 km apart along the coast of Alta and Baja California. In five periods of observations completed between 1991 and 1996, Chthamalus spp ., Pollicipes polymerus, and Balanus glandula settlement was consistently higher in the northern site, La Jolla (LJ), than in the southern site, La Salina (LS). For Chthamalus, the most abundant settler, settlement was higher in LJ in 58 out of 60 paired dates, by a mean factor of 141. In 1996, time series of temperature in about 15 m of water showed that the stratification was 72% higher, on average, and that the thermocline was shallower in LJ than in LS. Spectra of temperature showed that internal motions of tidal and higher frequencies were more energetic and closer to the surface in LJ compared to LS. In LJ changes in settlement were positively correlated with changes in stratification. These results suggest that high-frequency internal motions are important in the onshore transport of larvae. Low-frequency cooling events recorded in LJ apparently caused the energetic semidiurnal temperature variability to migrate from the bottom towards the surface, leading to the surface manifestation of the internal tide and surface internal tidal bores, which indicates that the surface nearshore bores occur in response to the shallowing of the thermocline. Tidal and higher frequency internal motions were more energetic when the thermocline was shallow during the low-frequency cooling events, than when it was deep and relatively weak during ordinary conditions. The major cooling event in LJ correlated with the local wind, suggesting local wind-driven upwelling. On the other hand, correlation of LS temperature with LJ temperature, winds, and sea level suggest propagation from the South. These results suggest that the low-frequency drops in temperature that modulate the nearshore internal tidal bores are caused by a combination of the local wind and events that propagate poleward, possibly as

  1. 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.

  2. Experimental studies on the thermal stratification and its influence on BLEVEs

    SciTech Connect

    Lin, Wensheng; Gong, Yanwu; Gao, Ting; Gu, Anzhong; Lu, Xuesheng

    2010-10-15

    The thermal stratification of Liquefied Petroleum Gas (LPG) and its effect on the occurrence of the boiling liquid expanding vapor explosion (BLEVE) have been investigated experimentally. Stratifications in liquid and vapor occur when the LPG tank is heated. The degree of the liquid stratification {beta} increases with an increasing heat flux and decreasing filling ratio. The effect of stratification on the BLEVE has been examined with depressurization tests of LPG. The results show that the pressure recovery for the stratified LPG ({beta} = 1.4) upon sudden depressurization is much lower than that for the isothermal LPG ({beta} = 1). It can be concluded that the liquid stratification decreases the liquid energy and the occurrence of the BLEVE. (author)

  3. 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.

  4. 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

  5. On numerically accurate finite element

    NASA Technical Reports Server (NTRS)

    Nagtegaal, J. C.; Parks, D. M.; Rice, J. R.

    1974-01-01

    A general criterion for testing a mesh with topologically similar repeat units is given, and the analysis shows that only a few conventional element types and arrangements are, or can be made suitable for computations in the fully plastic range. Further, a new variational principle, which can easily and simply be incorporated into an existing finite element program, is presented. This allows accurate computations to be made even for element designs that would not normally be suitable. Numerical results are given for three plane strain problems, namely pure bending of a beam, a thick-walled tube under pressure, and a deep double edge cracked tensile specimen. The effects of various element designs and of the new variational procedure are illustrated. Elastic-plastic computation at finite strain are discussed.

  6. 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.

  7. A Nonparametric Regression Approach to Control for Population Stratification in Rare Variant Association Studies

    PubMed Central

    Sha, Qiuying; Zhang, Kui; Zhang, Shuanglin

    2016-01-01

    Recently, there is increasing interest to detect associations between rare variants and complex traits. Rare variant association studies usually need large sample sizes due to the rarity of the variants, and large sample sizes typically require combining information from different geographic locations within and across countries. Although several statistical methods have been developed to control for population stratification in common variant association studies, these methods are not necessarily controlling for population stratification in rare variant association studies. Thus, new statistical methods that can control for population stratification in rare variant association studies are needed. In this article, we propose a principal component based nonparametric regression (PC-nonp) approach to control for population stratification in rare variant association studies. Our simulations show that the proposed PC-nonp can control for population stratification well in all scenarios, while existing methods cannot control for population stratification at least in some scenarios. Simulations also show that PC-nonp’s robustness to population stratification will not reduce power. Furthermore, we illustrate our proposed method by using whole genome sequencing data from genetic analysis workshop 18 (GAW18). PMID:27857226

  8. A Nonparametric Regression Approach to Control for Population Stratification in Rare Variant Association Studies.

    PubMed

    Sha, Qiuying; Zhang, Kui; Zhang, Shuanglin

    2016-11-18

    Recently, there is increasing interest to detect associations between rare variants and complex traits. Rare variant association studies usually need large sample sizes due to the rarity of the variants, and large sample sizes typically require combining information from different geographic locations within and across countries. Although several statistical methods have been developed to control for population stratification in common variant association studies, these methods are not necessarily controlling for population stratification in rare variant association studies. Thus, new statistical methods that can control for population stratification in rare variant association studies are needed. In this article, we propose a principal component based nonparametric regression (PC-nonp) approach to control for population stratification in rare variant association studies. Our simulations show that the proposed PC-nonp can control for population stratification well in all scenarios, while existing methods cannot control for population stratification at least in some scenarios. Simulations also show that PC-nonp's robustness to population stratification will not reduce power. Furthermore, we illustrate our proposed method by using whole genome sequencing data from genetic analysis workshop 18 (GAW18).

  9. Clarifying the role of principal stratification in the paired availability design.

    PubMed

    Baker, Stuart G; Lindeman, Karen S; Kramer, Barnett S

    2011-01-01

    The paired availability design for historical controls postulated four classes corresponding to the treatment (old or new) a participant would receive if arrival occurred during either of two time periods associated with different availabilities of treatment. These classes were later extended to other settings and called principal strata. Judea Pearl asks if principal stratification is a goal or a tool and lists four interpretations of principal stratification. In the case of the paired availability design, principal stratification is a tool that falls squarely into Pearl's interpretation of principal stratification as "an approximation to research questions concerning population averages." We describe the paired availability design and the important role played by principal stratification in estimating the effect of receipt of treatment in a population using data on changes in availability of treatment. We discuss the assumptions and their plausibility. We also introduce the extrapolated estimate to make the generalizability assumption more plausible. By showing why the assumptions are plausible we show why the paired availability design, which includes principal stratification as a key component, is useful for estimating the effect of receipt of treatment in a population. Thus, for our application, we answer Pearl's challenge to clearly demonstrate the value of principal stratification.

  10. Giant impacts, core stratification, and failure of the Martian dynamo

    NASA Astrophysics Data System (ADS)

    Arkani-Hamed, Jafar; Olson, Peter

    2010-07-01

    The close timing of the giant impacts and the cessation of the core dynamo of Mars at around 4 Ga suggest a possible causal relationship between these two events. We study the shock heating of the Martian interior caused by the impact that created Utopia basin, the largest of the 20 giant impact basins formed on Mars around 4 Ga. Using empirical scaling laws connecting the diameters of the basin and the projectile, we calculate the shock pressure distribution in Mars on the basis of Pierazzo et al.'s (1997) formula, which is then used to estimate the impact-induced temperature increase in the Martian mantle and core, adopting the “ordinary” and “foundering” shock heating mechanisms proposed by Watters et al. (2009) and impact velocities of 10 and 15 km/s. It is shown that the reduction of the heat flux out of the core due to impact heating of the overlying mantle is on the order of 0.03%-0.3% of the preimpact heat flux of the core (15 mW/m2), indicating that the impact heating of the mantle has insignificant effect on the thermal convection of the core. However, the shock waves that penetrate into the core directly and differentially heat the core in only a few minutes, which causes stable thermal stratification of the core within about a few years and diminishes the core convection and the thermally driven core dynamo within a few thousand years. Exhaustion of the impact heat and removal of the stratification is necessary to reestablish a superadiabatic temperature gradient and reactivate convection in the core. As the impact heat becomes concentrated in the upper parts of the core, the stratified part of the core first cools by conduction to the mantle and then later with a contribution from penetrative convection below the core-mantle boundary and by conduction into the deeper parts of the core. Depending on the impact velocity and the shock heating mechanisms, tens of millions of years may be needed to fully exhaust the core heat to the mantle, during

  11. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

    PubMed

    Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

    2015-09-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

  12. Temperature stratification from thermal diodes in solar hot water storage tank

    SciTech Connect

    Rhee, Jinny; Campbell, Andrew; Mariadass, Adele; Morhous, Branden

    2010-03-15

    In this brief note, we have experimentally measured the temperature stratification in a solar hot water storage tank resulting from a simulated solar heating load. Various modifications using a double chimney device that acts as a thermal diode were examined with the intent of maximizing temperature stratification. The greatest stratification was seen with a unique thermal diode arrangement named the express-elevator design, so-called for the direct hot water path from the bottom third of the tank to the top third. (author)

  13. IKKα regulates the stratification and differentiation of the epidermis: implications for skin cancer development

    PubMed Central

    Alameda, Josefa P.; Navarro, Manuel; Ramírez, Ángel; Page, Angustias; Suárez-Cabrera, Cristian; Moreno-Maldonado, Rodolfo; Paramio, Jesús M.; del Carmen Fariña, María; Río, Marcela Del; Fernández-Aceñero, María Jesús; Bravo, Ana; de los Llanos Casanova, María

    2016-01-01

    IKKα plays a mandatory role in keratinocyte differentiation and exerts an important task in non-melanoma skin cancer development. However, it is not fully understood how IKKα exerts these functions. To analyze in detail the role of IKKα in epidermal stratification and differentiation, we have generated tridimensional (3D) cultures of human HaCaT keratinocytes and fibroblasts in fibrin gels, obtaining human skin equivalents that comprise an epidermal and a dermal compartments that resembles both the structure and differentiation of normal human skin. We have found that IKKα expression must be strictly regulated in epidermis, as alterations in its levels lead to histological defects and promote the development of malignant features. Specifically, we have found that the augmented expression of IKKα results in increased proliferation and clonogenicity of human keratinocytes, and leads to an accelerated and altered differentiation, augmented ability of invasive growth, induction of the expression of oncogenic proteins (Podoplanin, Snail, Cyclin D1) and increased extracellular matrix proteolytic activity. All these characteristics make keratinocytes overexpressing IKKα to be at a higher risk of developing skin cancer. Comparison of genetic profile obtained by analysis of microarrays of RNA of skin equivalents from both genotypes supports the above described findings. PMID:27732959

  14. Spatial Stratification of Order As Used in Failure Analysis

    NASA Astrophysics Data System (ADS)

    Leonard, Robert H.; Bachlechner, Martina E.

    2007-03-01

    Silicon nitride deposited on silicon substrates has application in dielectric layers for microelectronics as well as in photovoltaics. During production and operation of components involving silicon/silicon nitride interfaces, stresses and strains can build up at various temperatures resulting in component failure. Using molecular dynamics simulations the influence of temperature and rate of externally applied strain on silicon/silicon nitride interfaces has been analyzed. The primary purpose of this research is to understand the mechanisms leading to the failure of these films. Analyses involving bond lengths and angles have been developed to gain insight into these mechanisms. Methods for stratifying bond lengths and bond angles into unique sub-populations on the basis of spatial orientation have been developed, and have given much insight to how the material behaves, particularly with regards to the Poisson effect. Possible extensions of this stratification method to primitive rings will also be examined. In combination with experimental observations, this analysis will deepen our understanding of the structural properties of silicon/silicon nitride interfaces.

  15. Thermal stratification drives movement of a coastal apex predator.

    PubMed

    Aspillaga, Eneko; Bartumeus, Frederic; Starr, Richard M; López-Sanz, Àngel; Linares, Cristina; Díaz, David; Garrabou, Joaquim; Zabala, Mikel; Hereu, Bernat

    2017-04-03

    A characterization of the thermal ecology of fishes is needed to better understand changes in ecosystems and species distributions arising from global warming. The movement of wild animals during changing environmental conditions provides essential information to help predict the future thermal response