Sequential Analysis (sequential + analysis)

Distribution by Scientific Domains


Selected Abstracts


Sequential analysis of lines of evidence,an advanced weight-of-evidence approach for ecological risk assessment

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 4 2006
Ruth N Hull
Abstract Weight-of-evidence (WOE) approaches have been used in ecological risk assessment (ERA) for many years. The approaches integrate various types of data (e.g., from chemistry, bioassay, and field studies) to make an overall conclusion of risk. However, the current practice of WOE has several important difficulties, including a lack of transparency related to how each line of evidence is weighted or integrated into the overall weight-of-evidence conclusion. Therefore, a sequential analysis of lines of evidence (SALE) approach has been developed that advances the practice of WOE. It was developed for an ERA of chemical stressors but also can be used for nonchemical stressors and is equally applicable to the aquatic and terrestrial environments. The sequential aspect of the SALE process is a significant advancement and is based on 2 primary ideas. First, risks can be ruled out with the use of certain lines of evidence, including modeled hazard quotients (HQs) and comparisons of soil, water, or sediment quality with conservative soil, water or sediment quality guidelines. Thus, the SALE process recognizes that HQs are most useful in ruling out risk rather than predicting risk to ecological populations or communities. Second, the SALE process provides several opportunities to exit the risk assessment process, not only when risks are ruled out, but also when magnitude of effect is acceptable or when little or no evidence exists that associations between stressors and effects may be causal. Thus, the SALE approach explicitly includes interaction between assessors and managers. It illustrates to risk managers how risk management can go beyond the simple derivation of risk-based concentrations of chemicals of concern to risk management goals based on ecological metrics (e.g., species diversity). It also can be used to stimulate discussion of the limitations of the ERA science, and how scientists deal with uncertainty. It should assist risk managers by allowing their decisions to be based on a sequential, flexible, and transparent process that includes direct toxicity risks, indirect risks (via changes in habitat suitability), and the spatial and temporal factors that can influence the risk assessment. [source]


Preferential hypermethylation of the Dickkopf-1 promoter in core-binding factor leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007
Rikio Suzuki
Summary The Dickkopf-1 (DKK1) gene product is an extracellular Wnt inhibitor. Hypermethylation of the DKK1 promoter results in transcriptional silencing and may play an important role in cancer development. Here, we investigated hypermethylation of the DKK1 promoter in patients with acute myeloid leukaemia (AML), especially core-binding factor (CBF) leukaemia. The methylation status of DKK1 was analysed using methylation-specific polymerase chain reaction in 47 patients with AML. DKK1 methylation was found in 14 (29·8%) patients, and more frequently in those with CBF leukaemia (6 of 12 patients), than in those with acute promyelocytic leukaemia (APL) (0 of 6 patients) (P = 0·03). In contrast, Wnt inhibitory factor-1 methylation was found in APL (4 of 6 patients) but not in CBF leukaemia (0 of 12 patients) (P = 0·001). Multivariate analyses suggested that DKK1 methylation was a risk factor for poorer overall survival. Sequential analysis using four paired samples obtained at diagnosis and relapse suggested that DKK1 methylation was involved in the progression of leukaemia. Therefore, DKK1 methylation may be involved in leukaemogenesis, especially in CBF leukaemia, and may be a useful prognostic marker in AML. [source]


Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C , an updated Cochrane review

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
J. Brok
Aliment Pharmacol Ther 2010; 32: 840,850 Summary Background, Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C. Aim, To meta-analyse the effect of adding ribavirin to interferon for chronic hepatitis C. Methods, The results of randomized trials were combined in cumulative meta-analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver-related morbidity plus all-cause mortality. Results, We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64,0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P -value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes. Conclusions, The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes. [source]


Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
L. L. Gluud
Aliment Pharmacol Ther 2010; 32: 859,871 Summary Background, The evidence concerning the use of isosorbide-mononitrate (IsMn) for oesophageal varices is equivocal. Aim, To assess the effects of IsMn for patients with oesophageal varices and no previous bleeding (primary prevention) or previous variceal bleeding (secondary prevention). Methods, Systematic review with meta-analyses of randomized trials on IsMn alone or with beta-blockers or endoscopic therapy for oesophageal varices. Electronic and manual searches were combined. Randomized trials on primary and secondary prevention were included. The primary outcome measure was mortality. Intention-to-treat random effects meta-analyses were performed. The robustness of the results was assessed in trial sequential analyses. Results, Ten randomized trials on primary and 17 on secondary prevention were included. Evidence of bias was identified. No apparent effect of IsMn on mortality compared with placebo or beta-blockers or IsMn plus beta-blockers vs. beta-blockers was identified. Compared with endoscopic therapy, IsMn plus beta-blockers had no apparent effect on bleeding, but did seem to reduce mortality in secondary prevention (RR 0.73, 95% CI 0.59,0.89), but not in primary prevention. The effect of IsMn plus beta-blockers on mortality in secondary prevention was not confirmed in trial sequential analysis. Conclusions, Isosorbide-mononitrate used alone or in combination with beta blockers does not seem to offer any reduction in bleeding in the primary or secondary prevention of oesophageal varices. Compared with endoscopic therapy, there may be a survival advantage in using IsMn and beta-blockers, but additional large multicentre trials are needed to verify this finding. [source]


Reconceptualizing Children's Suggestibility: Bidirectional and Temporal Properties

CHILD DEVELOPMENT, Issue 1 2005
Livia L. Gilstrap
Forty-one children (3 to 7 years) were exposed to a staged event and later interviewed by 1 of 41 professional interviewers. All interviews were coded with a detailed, mutually exclusive, and exhaustive coding scheme capturing adult behaviors (leading questions vs. neutral) and child behaviors (acquiescence vs. denial) in a temporally organized manner. Overall, interviewers' use of leading questions did not result in increased acquiescence as previously found. However, one specific type of leading question (i.e., inaccurate misleading) was followed by acquiescence. Lagged sequential analyses showed that it was possible to predict directly from child-to-child behavior, effectively skipping the intervening adult behavior. This result raises questions about the current conceptualization that suggestibility is driven by adult behaviors. [source]


Cardiac hypertrophy and failure: lessons learned from genetically engineered mice

ACTA PHYSIOLOGICA, Issue 1 2001
Y. Takeishi
Congestive heart failure is a major and growing public health problem. Because of improved survival of myocardial infarction patients produced by thrombolytic therapy or per-cutaneous revascularization it represents the only form of cardiovascular disease with significantly increased incidence and prevalence. Clinicians view this clinical syndrome as the final common pathway of diverse pathologies such as myocardial infarction and haemodynamic overload. Insights into mechanisms for heart failure historically derived from physiological and biochemical studies which identified compensatory adaptations for the haemodynamic burden associated with the pathological condition including utilization of the Frank Starling mechanism, augmentation of muscle mass, and neurohormonal activation to increase contractility. Therapy has largely been phenomenological and designed to prevent or limit the deleterious effects of these compensatory processes. More recently insights from molecular and cell biology have contributed to a more mechanistic understanding of potential causes of cardiac hypertrophy and failure. Many different analytical approaches have been employed for this purpose. These include the use of conventional animal models which permit serial observation of the onset and progression of heart failure and a sequential analysis of underlying biochemical and molecular events. Neonatal murine cardiomyocytes have been a powerful tool to examine in vitro subcellular mechanisms devoid of the confounding functional effects of multicellular preparations and heterogeneity of cell type. Finally, significant progress has been made by utilizing tissue from human cardiomyopathic hearts explanted at the time of orthotopic transplantation. Each of these methods has significant advantages and disadvantages. Arguably the greatest advance in our understanding of cardiac hypertrophy and failure over the past decade has been the exploitation of genetically engineered mice as biological reagents to study in vivo the effects of alterations in the murine genome. The power of this approach, in principle, derives from the ability to precisely overexpress or ablate a gene of interest and examine the phenotypic consequences in a cardiac specific post-natal manner. In contrast to conventional animal models of human disease which employ some form of environmental stress, genetic engineering involves a signal known molecular perturbation which produces the phenotype. [source]


A systematic approach to molecular quantitative determination of mixed chimaerism following allogeneic bone marrow transplantation: an analysis of its applicability in a group of patients with severe aplastic anaemia

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004
Rocío Hassan
Abstract:, Mixed chimaerism (MC) following allogeneic bone marrow transplantation (allo-BMT) is defined as the persistent cohabitation of haematopoietic cells from recipients and donors. Its kinetics, clinical implications and more efficient laboratory approaches for MC detection are the object of ongoing research in view of the possibility of developing useful markers. Here we describe a sequential analysis of chimaerism using variable number of tandem repeat (VNTR) polymerase chain reaction (PCR) followed by quantitative, fluorescent labelled, short tandem repeat (STR) PCR. A set of four, highly discriminative VNTR and four STR markers was used to assess chimaerism. Sensitivity and regression analysis indicated that this approach was reliable for routine application in a single BMT centre. We studied 12 patients with severe aplastic anaemia (SAA) who had received allo-BMT, and had been conditioned with cyclosphosphamide (Cy) with or without anti-thymocyte globulin (ATG). We found a 50% prevalence of MC in the whole group, with levels between 4% and 37% of recipient cells. A sustained stable MC pattern after BMT was characteristic of the Cy-only conditioned patients but was also recorded in one patient treated with the Cy + ATG regime who showed a sustained MC pattern over a period of 24 months post-BMT. In none of our patients, MC was associated with an increased risk of graft rejection in a median follow-up of 39.5 months. [source]


Sequential analysis of lines of evidence,an advanced weight-of-evidence approach for ecological risk assessment

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 4 2006
Ruth N Hull
Abstract Weight-of-evidence (WOE) approaches have been used in ecological risk assessment (ERA) for many years. The approaches integrate various types of data (e.g., from chemistry, bioassay, and field studies) to make an overall conclusion of risk. However, the current practice of WOE has several important difficulties, including a lack of transparency related to how each line of evidence is weighted or integrated into the overall weight-of-evidence conclusion. Therefore, a sequential analysis of lines of evidence (SALE) approach has been developed that advances the practice of WOE. It was developed for an ERA of chemical stressors but also can be used for nonchemical stressors and is equally applicable to the aquatic and terrestrial environments. The sequential aspect of the SALE process is a significant advancement and is based on 2 primary ideas. First, risks can be ruled out with the use of certain lines of evidence, including modeled hazard quotients (HQs) and comparisons of soil, water, or sediment quality with conservative soil, water or sediment quality guidelines. Thus, the SALE process recognizes that HQs are most useful in ruling out risk rather than predicting risk to ecological populations or communities. Second, the SALE process provides several opportunities to exit the risk assessment process, not only when risks are ruled out, but also when magnitude of effect is acceptable or when little or no evidence exists that associations between stressors and effects may be causal. Thus, the SALE approach explicitly includes interaction between assessors and managers. It illustrates to risk managers how risk management can go beyond the simple derivation of risk-based concentrations of chemicals of concern to risk management goals based on ecological metrics (e.g., species diversity). It also can be used to stimulate discussion of the limitations of the ERA science, and how scientists deal with uncertainty. It should assist risk managers by allowing their decisions to be based on a sequential, flexible, and transparent process that includes direct toxicity risks, indirect risks (via changes in habitat suitability), and the spatial and temporal factors that can influence the risk assessment. [source]


Why that, in that language, right now?

INTERNATIONAL JOURNAL OF APPLIED LINGUISTICS, Issue 3 2005
Code-switching, pedagogical focus
Dil de,i,imi; s,n,f içi etkile,im; diyalog çözümlemesi; ,ngilizce'nin yabanc, dil olarak okutuldu,u s,n,flar; ikinci yabanc, dil edinimi The study depicts the relationship between pedagogical focus and language choice in the language teaching/learning environment of English as a Foreign Language (EFL) at a Turkish university. The article presents the organisation of code-switching which is teacher-initiated and ,teacher-induced'. The data were collected from six beginner-level English classrooms. Transcripts of the lessons were examined using the conversation analysis (CA) method of sequential analysis in relation to the pedagogical focus, applying an adapted version of the classic CA question for interaction involving code-switching: "why that, in that language, right now?" The study demonstrates that code-switching in L2 classrooms is orderly and related to the evolution of pedagogical focus and sequence. Through their language choice, learners may display their alignment or misalignment with the teacher's pedagogical focus. Bu akademik çal,,ma, yabanc, dil olarak ,ngilizce eǧitim ve öǧretim veren bir Türk üniversitesi'ndeki eǧitsel (pedagojik) amaç ile dil seçimi aras,ndaki ili,kiyi incelemektedir. Dil deǧi,iminin (ayn, diyalog süresince birden fazla dilin kullan,lmas,) organizasyonunu öǧretmen-giri,imli ve öǧretmen-te,vikli (öǧretmenin bir ,ngilizce kelimenin Türkçe kar,,l,ǧ,n, sormas,) olarak aç,klanm,,t,r. Bu ara,t,rma için veriler s,n,f gözlemi metoduyla toplanm,,t,r. Bu metot 6 adet ba,lang,ç düzeyi ,ngilizce s,n,f,n,n ders kay,tlar,n,n sesli ve görüntülü toplanmas,yla yürütülmüttür. S,n,f içi diyalog döküman, diyalog çözümleme metodunun ard,,,k analiz yöntemine dayanarak diyalog çözümleme metodundaki klasik ,neden böyle?' ve ,neden ,imdi?' sorular,n,n öǧretmen-öǧrenci diyaloǧundaki dil deǧi,imine uyacak ,ekilde ,neden böyle?', ,neden bu dilde?' ve ,neden ,imdi?' olarak deǧi,tirilmi,tir. Bu ara,t,rma yabanc, dil s,n,flar,ndaki dil deǧi,iminin eǧitsel amaçlara baǧl, olarak deǧi,en kurall, bir yap,da olduǧunu ortaya koymaktad,r. Dil seçimleriyle öǧrenciler, öǧretmenin belirlediǧi eǧitsel amaca kat,l,p kat,lmad,klar,n, göstermektedirler. [source]


Self-injurious behaviour in Cornelia de Lange syndrome: 2. association with environmental events

JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 7 2009
J. Sloneem
Abstract Background Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour. Methods We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched for age, gender, level of intellectual disability and mobility. Descriptive analyses were used to determine the extent to which environmental events were associated with self-injury. Results Lag sequential analysis of the association between self-injurious behaviour and environmental events revealed no differences between the two groups in terms of either the number or degree of environmental associations. Conclusions The results suggest that the associations between the environment and self-injury in CdLS do not differ from those seen in the broader population of people with intellectual disability. By implication the social reinforcement hypothesis is equally applicable to both groups. [source]


Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C , an updated Cochrane review

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
J. Brok
Aliment Pharmacol Ther 2010; 32: 840,850 Summary Background, Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C. Aim, To meta-analyse the effect of adding ribavirin to interferon for chronic hepatitis C. Methods, The results of randomized trials were combined in cumulative meta-analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver-related morbidity plus all-cause mortality. Results, We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64,0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P -value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes. Conclusions, The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes. [source]


Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
L. L. Gluud
Aliment Pharmacol Ther 2010; 32: 859,871 Summary Background, The evidence concerning the use of isosorbide-mononitrate (IsMn) for oesophageal varices is equivocal. Aim, To assess the effects of IsMn for patients with oesophageal varices and no previous bleeding (primary prevention) or previous variceal bleeding (secondary prevention). Methods, Systematic review with meta-analyses of randomized trials on IsMn alone or with beta-blockers or endoscopic therapy for oesophageal varices. Electronic and manual searches were combined. Randomized trials on primary and secondary prevention were included. The primary outcome measure was mortality. Intention-to-treat random effects meta-analyses were performed. The robustness of the results was assessed in trial sequential analyses. Results, Ten randomized trials on primary and 17 on secondary prevention were included. Evidence of bias was identified. No apparent effect of IsMn on mortality compared with placebo or beta-blockers or IsMn plus beta-blockers vs. beta-blockers was identified. Compared with endoscopic therapy, IsMn plus beta-blockers had no apparent effect on bleeding, but did seem to reduce mortality in secondary prevention (RR 0.73, 95% CI 0.59,0.89), but not in primary prevention. The effect of IsMn plus beta-blockers on mortality in secondary prevention was not confirmed in trial sequential analysis. Conclusions, Isosorbide-mononitrate used alone or in combination with beta blockers does not seem to offer any reduction in bleeding in the primary or secondary prevention of oesophageal varices. Compared with endoscopic therapy, there may be a survival advantage in using IsMn and beta-blockers, but additional large multicentre trials are needed to verify this finding. [source]


Relation between inflammation and symptoms in asthma

ALLERGY, Issue 3 2009
I. Tillie-Leblond
Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids. [source]


The mechanical binding strengths of Helicobacter pylori BabA and SabA adhesins using an adhesion binding assay,ELISA, and its clinical relevance in Japan

MICROBIOLOGY AND IMMUNOLOGY, Issue 8 2010
Mitsuaki Nishioka
ABSTRACT To elucidate a potential role for H. pylori BabA and SabA adhesins in the pathogenesis of gastric mucosal lesions, the MBS of BabA and SabA was examined using an in-house ABA-ELISA. Ninety isolates from Japanese patients with gastric cancer (n= 43) and non-cancerous (n= 47) lesions were subjected to an ABA-ELISA which had been developed in-house, and sequential analysis of the babA2 middle region. The BabA-MBS was significantly higher in the cancer than the non-cancer group (P= 0.019), but there was no significant difference for SabA-MBS. A weak correlation between BabA-MBS and SabA-MBS (r= 0.418) was observed, the positive correlation being higher in the cancer than the non-cancer group (r= 0.598 and 0.288, respectively). The isolates were classified into two groups: a BabA-high-binding and a BabA-low-binding group (in comparison to the average for BabA-MBS). The average SabA-MBS in the BabA-high-binding group was significantly higher than in the BabA-low-binding group (P < 0.0001). Analysis of babA2 middle region diversity (AD1,5) revealed that AD2-type was predominant in isolates irrespective of BabA-MBS. H. pylori BabA-MBS might have an effect on SabA-MBS and relate to the severity of gastric disorders, including gastric cancer. Evaluation of MBS of the combined two adhesins would be helpful for predicting damage in the H. pylori infected stomach. [source]


Two-Stage Group Sequential Robust Tests in Family-Based Association Studies: Controlling Type I Error

ANNALS OF HUMAN GENETICS, Issue 4 2008
Lihan K. Yan
Summary In family-based association studies, an optimal test statistic with asymptotic normal distribution is available when the underlying genetic model is known (e.g., recessive, additive, multiplicative, or dominant). In practice, however, genetic models for many complex diseases are usually unknown. Using a single test statistic optimal for one genetic model may lose substantial power when the model is mis-specified. When a family of genetic models is scientifically plausible, the maximum of several tests, each optimal for a specific genetic model, is robust against the model mis-specification. This robust test is preferred over a single optimal test. Recently, cost-effective group sequential approaches have been introduced to genetic studies. The group sequential approach allows interim analyses and has been applied to many test statistics, but not to the maximum statistic. When the group sequential method is applied, type I error should be controlled. We propose and compare several approaches of controlling type I error rates when group sequential analysis is conducted with the maximum test for family-based candidate-gene association studies. For a two-stage group sequential robust procedure with a single interim analysis, two critical values for the maximum tests are provided based on a given alpha spending function to control the desired overall type I error. [source]