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PubMed1993

High antigenic cross-reactivity of the V3 consensus sequences of HIV-1 gp120.

The principal neutralization determinant (PND) of the human immunodeficiency virus type 1 (HIV-1) is located within the variable V3 region of the external envelope protein gp120. Although it is recognized that V3 sequences induce antibody response with restricted neutralization activity in vitro, we observed that the V3 consensus sequences representing North American/European and African isolates were highly cross-reactive, binding 94 and 77%, respectively, of sera collected from HIV-1 individuals originating from various parts of the world. Even HIV-1-positive sera from some East African residents, infected by strains whose V3 loop sequences are undoubtedly distinct from the North American/European consensus V3 loop sequence, reacted better to the V3 North American/European consensus peptide than to African-specific V3 sequences. Results indicate that the V3 consensus sequences represent the best candidates for optimal cross-reactivity with a wide variety of strains. Furthermore, using immunoassays for antibodies to prototype-specific V3 sequences, it is shown that HIV-1 strains related to the MN group are prevalent in West Africa, indicating either a West African origin of the MN-related viruses or more probably an introduction of this group of viruses through European/North American contacts.

Africa↗
PubMed2003

Expert consensus-based medication-use evaluation criteria for atypical antipsychotic drugs.

Medication-use criteria for the appropriate use of atypical antipsychotics were developed through a national consensus process utilizing an expert panel. A written survey was prepared which asked for opinions about options for psychopharmacologic interventions with seven antipsychotic drugs or categories (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, long-acting intramuscular decanoate ester preparations of conventional antipsychotics, and oral conventional antipsychotics) in 19 specific clinical situations. The survey was sent to 50 psychiatrists and psychiatric pharmacist specialists, 42 (84%) of whom completed the survey. The survey was formatted as a grid with rows listing various clinical situations and columns itemizing the various antipsychotic medications relevant to the situations. Responses were scored using a 9-point scale for rating the level of medical review required for any given decision. Consensus on each option was defined as a nonrandom distribution of scores by a chi-square goodness-of-fit test. Consensus was reached for 1179 of the 1230 items reviewed. Use of clozapine as a first-line therapy warranted prospective or mandated review for all diagnoses. Use of nonclozapine atypical agents for schizophrenia and schizoaffective and delusional disorders was judged to be the standard of care. Oral conventional antipsychotic agents were not considered the standard of care for any indication. Combination antipsychotic treatment always warranted at least concurrent review. Continued concerns about the use of ziprasidone and its cardiac effects were apparent. This study demonstrated the utility of a consensus-based process in addressing issues and practices not adequately addressed in the scientific literature.

Antipsychotic Agents↗
PubMed1998

A major component approach to presenting consensus sequences.

MOTIVATION: Summarizing and displaying the information contained in a set of aligned sequences is an important aid to identifying patterns within the sequences. A variety of forms of consensus sequences have been used previously to provide this information. However, these methods can cause a loss of information or introduce ambiguities into the consensus sequence, and some graphical approaches may become difficult to interpret due to visual distortion. RESULTS: We have developed a method to present a more precise and graphically clear view of a consensus sequence by using an approach based on defining the major components at each position in a sequence set. The major components are given in an ordered list and their frequencies are shown as histograms which can be colour coded to reflect conservative groupings. Minor components, a one-line character-based consensus sequence and information statistics can also be presented. As well as identifying the dominant sources of variation and conservation in the sequence set, the method also enables similarities and differences between subgroups of a sequence set to be readily assessed. AVAILIABILITY: On request from the authors. CONTACT: bcsmith@usthk.ust.hk, hxue@usthk. ust.hk

Amino Acid Sequence↗
PubMed1999

Neural network input representations that produce accurate consensus sequences from DNA fragment assemblies.

MOTIVATION: Given inputs extracted from an aligned column of DNA bases and the underlying Perkin Elmer Applied Biosystems (ABI) fluorescent traces, our goal is to train a neural network to determine correctly the consensus base for the column. Choosing an appropriate network input representation is critical to success in this task. We empirically compare five representations; one uses only base calls and the others include trace information. RESULTS: We attained the most accurate results from networks that incorporate trace information into their input representations. Based on estimates derived from using 10-fold cross-validation, the best network topology produces consensus accuracies ranging from 99.26% to >99.98% for coverages from two to six aligned sequences. With a coverage of six, it makes only three errors in 20 000 consensus calls. In contrast, the network that only uses base calls in its input representation has over double that error rate: eight errors in 20 000 consensus calls. CONTACT: allex@cs.wisc.edu

Base Sequence↗
PubMed2004

VisCoSe: visualization and comparison of consensus sequences.

We introduce visualization and comparison of consensus sequences (VisCoSe) as a WWW service and a stand-alone command line Perl script for visualizing and comparing consensus sequences of protein and nucleotide sequences. VisCoSe is the only interface available that simultaneously calculates consensus sequences of multiple data sets and automatically compares these consensus sequences. Furthermore, VisCoSe allows visualization of chemical properties of amino acids.

Algorithms↗
PubMed2004

A graph based algorithm for generating EST consensus sequences.

MOTIVATION: EST sequences constitute an abundant, yet error prone resource for computational biology. Expressed sequences are important in gene discovery and identification, and they are also crucial for the discovery and classification of alternative splicing. An important challenge when processing EST sequences is the reconstruction of mRNA by assembling EST clusters into consensus sequences. RESULTS: In contrast to the more established assembly tools, we propose an algorithm that constructs a graph over sequence fragments of fixed size, and produces consensus sequences as traversals of this graph. We provide a tool implementing this algorithm, and perform an experiment where the consensus sequences produced by our implementation, as well as by currently available tools, are compared to mRNA. The results show that our proposed algorithm in a majority of the cases produces consensus of higher quality than the established sequence assemblers and at a competitive speed. AVAILABILITY: The source code for the implementation is available under a GPL license from http://www.ii.uib.no/~ketil/bioinformatics/ CONTACT: ketil@ii.uib.no.

Algorithms↗
PubMed2005

Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology.

The 1996 American Heart Association consensus panel recommendations stated that pre-participation cardiovascular screening for young competitive athletes is justifiable and compelling on ethical, legal, and medical grounds. The present article represents the consensus statement of the Study Group on Sports Cardiology of the Working Group on Cardiac Rehabilitation and Exercise Physiology and the Working Group on Myocardial and Pericardial diseases of the European Society of Cardiology, which comprises cardiovascular specialists and other physicians from different European countries with extensive clinical experience with young competitive athletes, as well as with pathological substrates of sudden death. The document takes note of the 25-year Italian experience on systematic pre-participation screening of competitive athletes and focuses on relevant issues, mostly regarding the relative risk, causes, and prevalence of sudden death in athletes; the efficacy, feasibility, and cost-effectiveness of population-based pre-participation cardiovascular screening; the key role of 12-lead ECG for identification of cardiovascular diseases such as cardiomyopathies and channelopathies at risk of sudden death during sports; and the potential of preventing fatal events. The main purpose of the consensus document is to reinforce the principle of the need for pre-participation medical clearance of all young athletes involved in organized sports programmes, on the basis of (i) the proven efficacy of systematic screening by 12-lead ECG (in addition to history and physical examination) to identify hypertrophic cardiomyopathy-the leading cause of sports-related sudden death-and to prevent athletic field fatalities; (ii) the potential screening ability in detecting other lethal cardiovascular diseases presenting with ECG abnormalities. The consensus document recommends the implementation of a common European screening protocol essentially based on 12-lead ECG.

Adolescent↗
PubMed2006

The diagnosis of IBS in primary care: consensus development using nominal group technique.

BACKGROUND: The criteria used to identify and diagnose irritable bowel syndrome (IBS) in primary care are unclear, even though most patients are managed entirely in this setting. OBJECTIVE: To use a validated method of consensus development [Nominal Group Technique (Rand version)] (NGT-R) in order to construct a diagnostic framework for IBS appropriate to primary care. METHODS: NGT-R is a formal method of consensus development, which uses structured interaction within a group combined with statistical derivation of group judgements. The group comprised 10 GPs with a special interest in gastroenterology and two gastroenterologists, from 10 European countries. Mailed questionnaires elicited judgements on 242 scenarios for the diagnosis of IBS, within four domains of symptoms, social and lifestyle features, psychological features and investigations. Feedback of group decisions was followed by structured face-to-face interaction and private rescoring of the questionnaire. Consensus was defined as 10/12 ratings within one of three bands, 1-3 (disagreement), 4-6 (equivocal) or 7-9 (agreement). RESULTS: The defining features of IBS in primary care are alteration in bowel habit, bloating and abdominal pain, or discomfort or annoyance (the last reflecting important cultural differences in symptom description). These symptoms need to be present for at least 4 weeks. Supportive characteristics include female sex, family history of IBS, frequent clinic attendances, a recent major life event and a history of somatization behaviours. Abdominal examination was considered necessary in all patients and rectal examination, haemoglobin estimation and colonoscopy in those aged > 55 years. The subtypes of IBS are recognized, but the diagnostic process differs only in minor ways. Final consensus was reached on 46% of statements. CONCLUSION: The basis of IBS diagnosis in primary care differs from, and is less exclusive than, existing criteria. Few features are deemed essential for diagnosis, while psychosocial features, patient characteristics and contextual factors are important in increasing diagnostic probability. There are important cultural differences in the description of key symptoms. These results provide information on the defining characteristics of IBS and the diagnostic process, as it occurs in primary care, and can guide clinical practice.

Age Factors↗
PubMed1996

Moral consensus in public ethics: patient autonomy and family decision-making in the work of one state bioethics commission.

Focusing on the work of one bioethics commission, the New York State Task Force on Life and the Law, this article explores the role played by moral consensus in public ethics. Task Force members, who were appointed to represent diverse interests in New York State, identified a culturally strong value of individual autonomy as the ethical basis for their work on life-sustaining treatment. This moral consensus permitted the members to unite across their differences and develop public policy recommendations that substantially reformed a highly troubling New York law. However, the principle of autonomy insufficiently guides decisions by caring family members for incompetent adults in cases where little is known of patient preference. A different, more innovative moral vision is required--one that grants a more robust moral authority to the family. While government efforts that rely on moral consensus developed in a broad-based and well-reasoned manner can serve us well, in some cases the consensus will provide inadequate moral guidance. Government bioethical efforts must guard against the limits of moral vision in light of their disproportionate societal power.

Adult↗
PubMed2001

PROSPECT improves cis-acting regulatory element prediction by integrating expression profile data with consensus pattern searches.

Consensus pattern and matrix-based searches designed to predict cis-acting transcriptional regulatory sequences have historically been subject to large numbers of false positives. We sought to decrease false positives by incorporating expression profile data into a consensus pattern-based search method. We have systematically analyzed the expression phenotypes of over 6000 yeast genes, across 121 expression profile experiments, and correlated them with the distribution of 14 known regulatory elements over sequences upstream of the genes. Our method is based on a metric we term probabilistic element assessment (PEA), which is a ranking of potential sites based on sequence similarity in the upstream regions of genes with similar expression phenotypes. For eight of the 14 known elements that we examined, our method had a much higher selectivity than a naïve consensus pattern search. Based on our analysis, we have developed a web-based tool called PROSPECT, which allows consensus pattern-based searching of gene clusters obtained from microarray data.

5' Untranslated Regions↗
PubMed2002

Consensus Conference on Brain Tumor Definition for registration. November 10, 2000.

The Consensus Conference on Brain Tumor Definition was facilitated by the Central Brain Tumor Registry of the United States and held on November 10, 2000, in Chicago, Illinois, to reach multidisciplinary agreement on a standard definition of brain tumors for collecting and comparing data in the U.S. The Brain Tumor Working Group, convened in 1998 to determine the status of brain tumor collection in the U.S., outlined 4 recommendations of which the first 2 guided the discussion for the Consensus Conference: (1) standardization of a definition of primary brain tumors that is based on site alone, rather than on site and behavior, and that can be used by surveillance organizations in collecting these tumors; and (2) development of a reporting scheme that can be used for comparing estimates of primary brain tumors across registries. Consensus was reached on the collection of all primary brain tumor histologies found and reported in the brain or CNS ICD-O site codes (C70.0-C72.9 and C75.1-C75.3), including those coded benign and uncertain as well as those coded malignant. In addition, a comprehensive listing of histologies occurring in the brain and CNS, based on the CBTRUS grouping scheme, was formulated to provide a template for reporting in accordance with the second recommendation of the Brain Tumor Working Group. With consensus achieved on the first 2 recommendations, the stage is set to move forward in estimating additional resources necessary for the collection of these tumors, including funding, training for cancer registrars, identifying quality control measures, and developing computerized edit checks, as outlined in the last 2 recommendations of the Brain Tumor Working Group.

Brain Neoplasms↗
PubMed1999

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Adolescent↗
PubMed1999

Cost analysis in the Department of Veterans Affairs: consensus and future directions.

OBJECTIVES: In 1997, the Management Decision and Research Center of the Department of Veterans Affairs convened cost experts and health economists in a working meeting. Its goal was to provide consensus guidelines for conducting cost analyses in managed care systems, such as VA, that do not have encounter-level cost data or that do not prepare itemized patient bills. The impetus for the meeting was that too often computer-based cost data were proposed or used in studies that were inappropriate for the question being addressed. There was also a sense that often great effort was being expended by VA health economists "reinventing the wheel" in developing new cost components for each study. METHODS: A group of 45 VA and non-VA health economists, health researchers, and policy-makers attended a 2 day working meeting organized around a series of case vignettes to identify areas of consensus, controversy, and gaps in knowledge. RESULTS: Consensus emerged in the following four areas: (1) Cost Methods. A "hybrid model" was identified as the current standard of cost analysis in VA and entails mixing "micro-costing" primary data collection and "gross-cost" computer-based methods to reflect resource-use variations that are essential to the research question. (2) Cost Infrastructure. VA is developing a new, but unevaluated, costing system that could allow for computer-based cost analyses at much finer levels of detail than is currently possible. (3) Data Quality. Ongoing data validation of existing and developing cost databases is needed, especially concerning interfacility variation. (4) Dissemination. A new cost data center was recommended to provide training, information dissemination, and coordination. CONCLUSIONS: Consensus was reached about the hybrid model as the current paradigm for cost analysis in systems like VA.

Costs and Cost Analysis↗
PubMed2004

Achieving consensus across diverse stakeholders on quality measures for mental healthcare.

OBJECTIVE: Quality-improvement efforts are hindered by a lack of consensus on meaningful and feasible measures of care. The objective of this study was to develop a core set of quality measures for mental health and substance-related care that are meaningful to stakeholders, feasible to implement, and broadly representative of diverse dimensions of the mental health system. METHOD: A 12-member panel of stakeholders from national organizations evaluated 116 process measures in a 2-stage modified Delphi consensus development process. Drawing on a conceptual framework and literature review, panelists rated each measure on 7 domains using a 9-point scale (1 = best). Measures were then mapped to a framework of system dimensions to identify a core set with the highest ratings for system characteristics within each dimension. RESULTS: Twenty-eight measures were identified assessing treatment (12), access (2), assessment (2), continuity (4), coordination (2), prevention (1), and safety (5). Overall, mean ratings for meaningfulness were: clinical importance 2.29; perceived gap between actual and optimal care 2.59; association between improved performance and outcome 2.61. For feasibility, mean ratings were clarity of specifications 3.39; acceptability of data collection burden 4.77; and adequacy of case mix adjustment 4.20. The measures address a range of treatment modalities, clinical settings, diagnostic categories, vulnerable populations, and other dimensions of mental healthcare. CONCLUSIONS: A structured consensus process identified a core set of quality measures that are meaningful and feasible to multiple stakeholders, as well as broadly representative of the mental healthcare system. By yielding quantitative assessments of meaningfulness, feasibility and degree of consensus among stakeholders, these results can inform ongoing national efforts to adopt common quality measures for mental healthcare.

Adult↗
PubMed1995

Reaching consensus: the process of recommending treatment decisions for Alzheimer's patients.

Observational and interview data obtained from nurse caregivers and family members of patients with late-stage Alzheimer's disease were analyzed to explicate the nursing role in advance proxy planning. A four-phase model, Achieving Consensus: Decision Making to Determine Treatment Options for Patients with Alzheimer's Disease, was developed. Patient decline, family coping, professional development of nursing staff, and nursing unit philosophy were community characteristics found to be important antecedents to the process of reaching consensus. Achieving consensus constructs included interactive process components of patient, family, and staff adjustment, caring, and knowing. Timing and trust were influential catalysts to family and staff readiness factors for achieving consensus. Outcomes were the advice provided by staff and the family conference where treatment options were determined. Consequences included the advance proxy plan and patient care.

Adaptation, Psychological↗
PubMed2006

Consensus statement on injury definitions and data collection procedures in studies of football (soccer) injuries.

BACKGROUND: Variations in definitions and methodologies have created differences in the results and conclusions obtained from studies of football (soccer) injuries; this has made interstudy comparisons difficult. PROCEDURE: An Injury Consensus Group was established under the auspices of Fédération Internationale de Football Association Medical Assessment and Research Centre. Using a nominal group consensus model approach, a working document that identified the key issues related to definitions, methodology, and implementation was discussed by members of the group during a 2-day meeting. After this meeting, iterative draft statements were prepared and circulated to the members of the group for comment before the final consensus statement was produced. RESULTS: Definitions of injury, recurrent injury, severity, and training and match exposures in football, together with criteria for classifying injuries in terms of location, type, diagnosis, and causation are proposed. Proforma for recording players' baseline information, injuries, and training and match exposures are presented. Recommendations are made on how the incidence of match and training injuries should be reported and a checklist of issues and information that should be included in published reports of studies of football injuries is presented. CONCLUSIONS: The definitions and methodology proposed in the consensus statement will ensure that consistent and comparable results will be obtained from studies of football injuries.

Athletic Injuries↗
PubMed2006

Proposed quality measures for palliative care in the critically ill: a consensus from the Robert Wood Johnson Foundation Critical Care Workgroup.

For critically ill patients and their loved ones, high-quality health care includes the provision of excellent palliative care. To achieve this goal, the healthcare system needs to identify, measure, and report specific targets for quality palliative care for critically ill or injured patients. Our objective was to use a consensus process to develop a preliminary set of quality measures to assess palliative care in the critically ill. We built on earlier and ongoing efforts of the Robert Wood Johnson Foundation Critical Care End-of-Life Peer Workgroup to propose specific measures of the structure and process of palliative care. We used an informal iterative consensus process to identify and refine a set of candidate quality measures. These candidate measures were developed by reviewing previous literature reviews, supplementing the evidence base with recently published systematic reviews and consensus statements, identifying existing indicators and measures, and adapting indicators from related fields for our objective. Among our primary sources, we identified existing measures from the Voluntary Hospital Association's Transformation of the ICU program and a government-sponsored systematic review performed by RAND Health to identify palliative care quality measures for cancer care. Our consensus group proposes 18 quality measures to assess the quality of palliative care for the critically ill and injured. A total of 14 of the proposed measures assess processes of care at the patient level, and four measures explore structural aspects of critical care delivery. Future research is needed to assess the relationship of these measures to desired health outcomes. Subsequent measure sets should also attempt to include outcome measures, such as patient or surrogate satisfaction, as the field develops the means to rigorously measure such outcomes. The proposed measures are intended to stimulate further discussion, testing, and refinement for quality of care measurement and enhancement.

Continuity of Patient Care↗
PubMed1992

Site-directed mutagenesis of the hydrogenase signal peptide consensus box prevents export of a beta-lactamase fusion protein.

A secretion vector, pVN1, expressing the [NiFe] hydrogenase signal peptide of Desulfovibrio vulgaris Hildenborough fused to beta-lactamase from Escherichia coli was constructed in order to study the unusual characteristics of hydrogenase signal peptides, which share a strictly conserved sequence, the consensus box: R-R-X-F-X-K. Although the hydrogenase signal peptide-beta-lactamase fusion protein was processed much more slowly than the fusion of beta-lactamase with its own signal peptide, the system mimicked several features expected for hydrogenase biosynthesis in E. coli, including increased export under anaerobic conditions. Site-directed mutagenesis of R(-28), the first arginine residue of the consensus box, to a glutamate completely inhibited export and processing of the fusion protein. The same mutation of R(-33), located outside the consensus box, had almost no effect. The data indicate a specific role for the consensus box sequence in the export mechanism for hydrogenase.

Amino Acid Sequence↗