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Effectiveness of an experimental consensus phytase in improving dietary phytate-phosphorus utilization by weanling pigs.

Consensus phytase is a new biosynthetic, heat-stable enzyme derived from the sequences of multiple homologous phytases. Two experiments were conducted to determine its effectiveness, relative to inorganic P and a mutant enzyme of Escherichia coli phytase (Mutant-EP), in improving dietary phytate-P availability to pigs. In Exp. 1, 36 pigs (3 wk old, 7.00 +/- 0.24 kg of BW) were fed a low-P corn-soybean meal basal diet plus consensus phytase at 0, 250, 500, 750, 1,000, or 1,250 U/kg of feed for 5 wk. Plasma inorganic P concentration, plasma alkaline phosphatase activity, bone strength, and overall ADG and gain:feed ratio of pigs were improved (P < 0.05) by consensus phytase in both linear (R2 = 0.20 to 0.70) and quadratic (R2 = 0.30 to 0.70) dose-dependent fashions. In Exp. 2, 36 pigs (4 wk old, 9.61 +/- 0.52 kg BW) were fed the basal diet + inorganic P at 0.1 or 0.2%, consensus phytase at 750 or 450 U/kg of feed, Mutant-EP at 450 U/kg of feed, or 225 U consensus + 225 U Mutant-EP/kg of feed. Pigs fed 750 U of consensus phytase or 450 U of Mutant-EP/kg feed had plasma inorganic concentrations and bone strength that fell between those of pigs fed 0.1 or 0.2% inorganic P. These two measures were 16 to 29% lower (P < 0.05) in pigs fed 450 U of consensus phytase/kg of feed than those of pigs fed 0.2% inorganic P. Plasma inorganic P concentrations were 14 to 29% higher (P < 0.05) in pigs fed Mutant-EP vs. consensus phytase at 450 U/kg at wk 2 and 3. In conclusion, the experimental consensus phytase effectively releases phytate P from the corn-soy diet for weanling pigs. The inorganic P equivalent of 750 U of consensus phytase/kg of feed may fall between 0.1 and 0.2%, but this requires further determination.

6-Phytase↗

Words without action? The production, dissemination, and impact of consensus recommendations.

When existing evaluations find little or no evidence of consensus recommendations leading to action, one can justifiably ask why so much of this review was dedicated to analyzing alternative ways of producing such "words without action." There are, however, at least two reasons why consensus recommendations should be produced with care and attention to validity. First, recommendations do sometimes have an impact on behavior as a consequence of mere dissemination activity--the Dutch program, for instance, was more successful than most. This success may occur when the target audience is already particularly receptive to change and the message is timely and delivered by a credible source in a clinically relevant way. Thus, although "such a conjunction of favorable conditions is probably the exception rather than the rule for consensus topics" (46, 240) it does happen. Second, the output from consensus processes is increasingly a potential input to other processes. Consensus recommendations can be used as the criteria for evaluation and appraisal aimed at changing practice behavior, making administrative decisions on resource allocation, or defining research protocols. For instance, quality assurance activities, such as peer assessment, practitioner certification, or utilization review, are actively seeking criteria with which to make judgments and elicit changes in practice to improve the quality of care. Funding agencies are looking for information to help make reimbursement, capital expenditure, or fee-for-service decisions on cessation of insurance for particular procedures or approaches. These uses of the consensus criteria are potentially major and controversial. Therefore, even if dissemination rarely leads to action, consensus processes should still be done carefully and with valid techniques. The use of their recommendations embedded within other activities may well lead to (forced) changes in behavior. On ethical grounds alone, we should be as sure as possible that the behavior changes being implied and encouraged are indeed advisable. For these reasons, the review describes the decision points in the production process for consensus recommendations as a start on the development of a set of recognized standards. The review offers a critical appraisal of the various methodological choices available at each decision point. The seven decision points are selecting a topic, picking the consensus group, providing background preparation, identifying information inputs, choosing a group judgment process, defining the criteria for recommendations, and choosing a report preparation procedure and format. At least two important points emerged from this review. First, the research is often not well enough developed to give clear indications for many of the choices on what is the "best" alternative.(ABSTRACT TRUNCATED AT 400 WORDS)

Canada↗

Majority-rule reduced consensus trees and their use in bootstrapping.

Bootstrap analyses are usually summarized with majority-rule component consensus trees. This consensus method is based on replicated components and, like all component consensus methods, it is insensitive to other kinds of agreement between trees. Recently developed reduced consensus methods can be used to summarize much additional agreement on hypothesised phylogenetic relationships among multiple trees. The new methods are "strict" in the sense that they require agreement among all the trees being compared for any relationships to be represented in a consensus tree. Majority-rule reduced consensus methods are described and their use in bootstrap analyses is illustrated with a hypothetical and a real example. The new methods provide summaries of the bootstrap proportions of all n-taxon statements/partitions and facilitate the identification of hypotheses of relationships that are supported by high bootstrap proportions, in spite of a lack of support for particular components or clades. In practice majority-rule reduced consensus profiles may contain many trees. The size of the profile can be reduced by constraints on minimal bootstrap proportions and/or cardinality of the included trees. Majority-rule reduced consensus trees can also be selected a posteriori from the profile. Surrogates to the majority-rule reduced consensus methods using partition tables or tree pruning options provided by widely used phylogenetic inference software are also described. The methods are designed to produce more informative summaries of bootstrap analyses and thereby foster more informed assessment of the strengths and weaknesses of complex phylogenetic hypotheses.

Animals↗

The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: pediatric basic and advanced life support.

This publication contains the pediatric and neonatal sections of the 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (COSTR). The consensus process that produced this document was sponsored by the International Liaison Committee on Resuscitation (ILCOR). ILCOR was formed in 1993 and consists of representatives of resuscitation councils from all over the world. Its mission is to identify and review international science and knowledge relevant to cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) and to generate consensus on treatment recommendations. ECC includes all responses necessary to treat life-threatening cardiovascular and respiratory events. The COSTR document presents international consensus statements on the science of resuscitation. ILCOR member organizations are each publishing resuscitation guidelines that are consistent with the science in this consensus document, but they also take into consideration geographic, economic, and system differences in practice and the regional availability of medical devices and drugs. The American Heart Association (AHA) pediatric and the American Academy of Pediatrics/AHA neonatal sections of the resuscitation guidelines are reprinted in this issue of Pediatrics (see pages e978-e988). The 2005 evidence evaluation process began shortly after publication of the 2000 International Guidelines for CPR and ECC. The process included topic identification, expert topic review, discussion and debate at 6 international meetings, further review, and debate within ILCOR member organizations and ultimate approval by the member organizations, an Editorial Board, and peer reviewers. The complete COSTR document was published simultaneously in Circulation (International Liaison Committee on Resuscitation. 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2005;112(suppl):73-90) and Resuscitation (International Liaison Committee on Resuscitation. 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2005;67:271-291). Readers are encouraged to review the 2005 COSTR document in its entirety. It can be accessed through the CPR and ECC link at the AHA Web site: www.americanheart.org. The complete publication represents the largest evaluation of resuscitation literature ever published and contains electronic links to more detailed information about the international collaborative process. To organize the evidence evaluation, ILCOR representatives established 6 task forces: basic life support, advanced life support, acute coronary syndromes, pediatric life support, neonatal life support, and an interdisciplinary task force to consider overlapping topics such as educational issues. The AHA established additional task forces on stroke and, in collaboration with the American Red Cross, a task force on first aid. Each task force identified topics requiring evaluation and appointed international experts to review them. A detailed worksheet template was created to help the experts document their literature review, evaluate studies, determine levels of evidence, develop treatment recommendations, and disclose conflicts of interest. Two evidence evaluation experts reviewed all worksheets and assisted the worksheet reviewers to ensure that the worksheets met a consistently high standard. A total of 281 experts completed 403 worksheets on 275 topics, reviewing more than 22000 published studies. In December 2004 the evidence review and summary portions of the evidence evaluation worksheets, with worksheet author conflict of interest statements, were posted on the Internet at www.C2005.org, where readers can continue to access them. Journal advertisements and e-mails invited public comment. Two hundred forty-nine worksheet authors (141 from the United States and 108 from 17 other countries) and additional invited experts and reviewers attended the 2005 International Consensus Conference for presentation, discussion, and debate of the evidence. All 380 participants at the conference received electronic copies of the worksheets. Internet access was available to all conference participants during the conference to facilitate real-time verification of the literature. Expert reviewers presented topics in plenary, concurrent, and poster conference sessions with strict adherence to a novel and rigorous conflict of interest process. Presenters and participants then debated the evidence, conclusions, and draft summary statements. Wording of science statements and treatment recommendations was refined after further review by ILCOR member organizations and the international editorial board. This format ensured that the final document represented a truly international consensus process. The COSTR manuscript was ultimately approved by all ILCOR member organizations and by an international editorial board. The AHA Science Advisory and Coordinating Committee and the editor of Circulation obtained peer reviews of this document before it was accepted for publication. The most important changes in recommendations for pediatric resuscitation since the last ILCOR review in 2000 include: Increased emphasis on performing high quality CPR: "Push hard, push fast, minimize interruptions of chest compression; allow full chest recoil, and don't provide excessive ventilation" Recommended chest compression-ventilation ratio: For lone rescuers with victims of all ages: 30:2 For health care providers performing 2-rescuer CPR for infants and children: 15:2 (except 3:1 for neonates) Either a 2- or 1-hand technique is acceptable for chest compressions in children Use of 1 shock followed by immediate CPR is recommended for each defibrillation attempt, instead of 3 stacked shocks Biphasic shocks with an automated external defibrillator (AED) are acceptable for children 1 year of age. Attenuated shocks using child cables or activation of a key or switch are recommended in children <8 years old. Routine use of high-dose intravenous (IV) epinephrine is no longer recommended. Intravascular (IV and intraosseous) route of drug administration is preferred to the endotracheal route. Cuffed endotracheal tubes can be used in infants and children provided correct tube size and cuff inflation pressure are used. Exhaled CO2 detection is recommended for confirmation of endotracheal tube placement. Consider induced hypothermia for 12 to 24 hours in patients who remain comatose following resuscitation. Some of the most important changes in recommendations for neonatal resuscitation since the last ILCOR review in 2000 include less emphasis on using 100% oxygen when initiating resuscitation, de-emphasis of the need for routine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born to mothers with meconium staining of amniotic fluid, proven value of occlusive wrapping of very low birth weight infants <28 weeks' gestation to reduce heat loss, preference for the IV versus the endotracheal route for epinephrine, and an increased emphasis on parental autonomy at the threshold of viability. The scientific evidence supporting these recommendations is summarized in the neonatal document (see pages e978-e988).

Child↗

[Preliminary evaluation of Chile's First Citizen Consensus Conference].

This piece provides an initial assessment of the First Citizen Consensus Conference, an event held in the city of Santiago, Chile, from 22-24 November 2003, on the subject of "The Management of My Medical Record." This conference was the first citizen consensus conference that has been held in Chile as well as the first such conference in Latin America. Consensus conferences were devised by the Danish Board of Technology in 1987 as a way to assess science and technology issues through discussions between experts and a panel of lay persons. At the end of a consensus conference, the lay persons express their opinions and recommendations in a consensus report that is directed at policymakers, decision-makers, and the public in general. The objective of a consensus conference is to bridge the gaps that routinely exist among the general public, experts, and elected officials. So far, the Danish Board of Technology has organized more than 20 of these conferences, using a methodology that has become established as a model. Taking into account the changes that have occurred in the relationship between science and society at large, the Pan American Health Organization has decided to support the holding of consensus conferences in Latin America and the Caribbean. The First Citizen Consensus Conference adapted the Danish methodology to conditions in Chile, and this piece assesses the modifications that were made. In addition, some 6 to 12 months after the conference, there will be an external evaluation of the outcomes and impact of the conference, especially in the communications media, public debate, decision-making, and perceptions of the persons who were involved. Despite the criticisms made in this piece and some shortcomings that are pointed out, the First Citizen Consensus Conference achieved all of its objectives and will serve as an excellent model for similar conferences in other countries of the Americas.

Chile↗

Quality assurance in radiation therapy: clinical and physical aspects. Consensus of best current management: the starting point for clinical quality assessment.

Consensus of best current management developed by a rational and deliberative process can provide the basis for clinical quality assessment. Unfortunately, it is not always possible to arrive at a consensus at all cancer sites, and this generally indicates areas where clinical research is needed. Assessing the quality of care in these situations presents special problems. When it is possible to arrive at consensus in a specific disease, this consensus should detail appropriate pretreatment evaluation and the details of the treatment. Committees of experts for each specific disease site can formulate the consensus and must document their decisions based on information from the current world literature. A carefully thought out and documented consensus can then provide the basis for the development of process based questionnaires in assessing quality. We have observed that individuals formulating consensus of best current management do not strictly follow their own criteria, and that compliance in various strata of practice throughout the United States shows a greater deviation from consensus than anticipated and indeed this deviation crosses all types of practice. It was then necessary to conduct outcome surveys in the same patients to validate the processes of care by showing a correlation of process performance with outcome or indeed to change our concepts of best current management. We recognize from these outcome studies that relatively few processes have direct association with outcome and the majority of our consensus points relate to either good general patient management or items important to individual patients but not to large groups of patients. In addition to validating processes through outcome correlations, we have found that process verification is important. We have observed quite different outcomes for two groups of patients with Hodgkin's disease treated with the same processes (i.e., mantle field technology and adequate radiation dose, etc.). We were unable to identify the reason for an increased failure rate in one group of these patients until we looked at each individual mantle port film from the two groups of patients. We then identified that one facility was not including the Hodgkin's disease in the treatment portal due to poor technical performance. We believe that this program of process verification may be important in evaluating quality for any disease site. Data will be presented that illustrates the above problems.

Adult↗

Rural/urban elderly and siblings: their value consensus.

Consensus is the level of agreement about life felt among kin and has been identified as a dimension of family solidarity with important implications for the family network. This investigation studied the factors contributing to the consensus between older adults (age sixty-five and older) and the sibling with whom they had the most contact. Respondents (N = 275) lived in a rural/urban area. Seven independent variables were entered into a multiple-regression model to determine their relative importance to consensus of the sibling relationship. Results showed that 7 percent of the variance in consensus could be explained. Filial expectations, educational disparity, and the brother/sister link were the only variables of relative importance to older adult/sibling consensus. There was greater consensus when there were fewer expectations of the sibling, similarity of educational backgrounds, and when the respondent was male and his sibling was female. Brother/sister and brother/brother links, residential proximity, communication by mail or telephone, helping behaviors, and marital status were of no relative importance to consensus. The results suggest that factors previously found to be associated with intergenerational consensus may vary in their importance to intragenerational consensus.

Aged↗

Possibilities of consensus: toward democratic moral discourse.

The concept of consensus is often appealed to in discussions of biomedical ethics and applied ethics, and it plays an important role in many influential ethical theories. Consensus is an especially influential notion among theorists who reject ethical realism and who frame ethics as a practice of discourse rather than a body of objective knowledge. It is also a practically important notion when moral decision making is subject to bureaucratic organization and oversight, as is increasingly becoming the case in medicine. Two models of consensus are examined and criticized: pluralistic consensus and overlapping consensus. As an alternative to these models, the paper argues that consensus refers to the dialogic aspects of a broader normative conception of democratic moral agency. When the preconditions for that dialogic democratic practice are met, consensus has a justificatory role in ethics; when they are not, consensus, as distinct from mere agreement, does not emerge and can have no moral authority.

Bioethical Issues↗

The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators.

OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Humans↗

Applications of consensus polymerase chain reaction with subsequent electrophoretic distinction of amplificates.

Conserved sequences within gene families permit the design of consensus primers that match several members of a given class of homologous genes. Polymerase chain reaction (PCR) products obtained with such consensus primers were characterized by restriction mapping or single-strand conformation polymorphism (SSCP) analysis, using precast polyacrylamide minigels and automated silver staining. Examples for the electrophoretic distinction of consensus amplificates are presented in the fields of guanylyl cyclase expression studies and in the determination of B-cell clonality in human blood samples. Guanylyl cyclase expression in inner ear tissues of guinea pigs was investigated by reverse transcription PCR using consensus primers with specificity for the subclass of particulate guanylyl cyclases. The resulting PCR products were assigned to three representatives of this group by restriction mapping. The consensus PCR approach enabled the detection of an unexpected receptor type, namely guanylyl cyclase C, in the inner ear. The distinction by SSCP analysis of denatured consensus amplificates was appropriate for the identification of clone-specifically rearranged immunoglobulin heavy chain genes of B-lymphocytes. Genomic DNA isolated from blood samples of leukemia patients served as the template for the consensus amplification of clone-specific VDJ rearrangements. Rapid distinction and re-identification of consensus PCR products was achieved by SSCP analysis for regular antigen receptor rearrangements and for t(14; 18) translocations. The potential of these procedures for detecting leukemia or lymphoma clones when monitoring minimal residual disease was assessed.

Animals↗

Mature B-cell lymphoma/leukemia in children and adolescents: intergroup pathologist consensus with the revised European-American Lymphoma Classification.

BACKGROUND: The Revised European-American Lymphoma (R.E.A.L.) Classification criteria were evaluated in the international protocol FAB LMB 96 Treatment of Mature B-cell Lymphoma/Leukemia: A SFOP LMB 96/CCG-5961/UKCCSG NHL 9600 Cooperative Study. This includes B-lineage lymphomas: Burkitt's lymphoma (including ALL-L3); high-grade B-cell lymphoma, Burkitt-like; diffuse large B-cell lymphoma (excluding anaplastic large cell Ki-1 lymphoma). PATIENTS AND METHODS: Cases were independently reviewed by eight hematopathologists from the three cooperative national groups (two SFOP, two CCG, four UKCCSG), without prior discussion of classification criteria or guidelines for case rejection. Consensus diagnosis was determined by each national cooperative group, and final consensus diagnosis established when at least two national consensus diagnoses were in agreement, or following group agreement at a multiheaded microscope. RESULTS: Two hundred eight cases were reviewed, with final consensus diagnosis established in two hundred three. The percent agreement of each group's national consensus diagnosis with final consensus diagnosis was 86%, 86% and 71%. The percent agreement of the group's national consensus diagnosis with final consensus diagnosis for Burkitt's and diffuse large B-cell lymphoma were 88% and 80%, respectively, but only 42% for Burkitt-like lymphoma. CONCLUSIONS: International panel review of mature B-cell lymphoma/leukemia in children and adolescents highlighted difficulties in subclassification, particularly with Burkitt-like, which is a 'provisional entity' in the R.E.A.L. Classification. The absence of previous discussion of classification and guidelines for case rejection may in part explain the discrepancy between pathologists. These results underline that morphology may need to be complemented by other studies, such as molecular genetic and cytogenetics, to discriminate between the mature B-cell lymphomas.

Adolescent↗

Multipolar consensus for phylogenetic trees.

Collections of phylogenetic trees are usually summarized using consensus methods. These methods build a single tree, supposed to be representative of the collection. However, in the case of heterogeneous collections of trees, the resulting consensus may be poorly resolved (strict consensus, majority-rule consensus, ...), or may perform arbitrary choices among mutually incompatible clades, or splits (greedy consensus). Here, we propose an alternative method, which we call the multipolar consensus (MPC). Its aim is to display all the splits having a support above a predefined threshold, in a minimum number of consensus trees, or poles. We show that the problem is equivalent to a graph-coloring problem, and propose an implementation of the method. Finally, we apply the MPC to real data sets. Our results indicate that, typically, all the splits down to a weight of 10% can be displayed in no more than 4 trees. In addition, in some cases, biologically relevant secondary signals, which would not have been present in any of the classical consensus trees, are indeed captured by our method, indicating that the MPC provides a convenient exploratory method for phylogenetic analysis. The method was implemented in a package freely available at http://www.lirmm.fr/~cbonnard/MPC.html

Algorithms↗

The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon.

Consensus interferon (Infergen) is a wholly synthetic type I interferon (IFN), developed by scanning several interferon-alpha nonallelic subtypes and assigning the most frequently observed amino acid in each position, resulting in a consensus sequence. The antiviral, antiproliferative, NK cell activation activity, cytokine induction, and interferon-stimulated gene-induction activity of consensus interferon has been compared with naturally occurring type I interferons. In all of these comparisons, consensus interferon had a higher activity when compared, on a mass basis, with IFN-alpha 2a and IFN-alpha 2b, although the activity was the same for all of these parameters on an antiviral unit basis. That a synthetic type I interferon could have higher activities than naturally occurring molecules is surprising and may be a result of the higher affinity for the array of type I interferon receptors demonstrated for consensus interferon when compared with IFN-alpha. In contrast, consensus interferon was shown to be an inferior inducer of IL-1 beta when compared with IFN-alpha. These results may reflect differential binding to multiple accessory proteins interacting with a type I interferon receptor. These unique biologic properties may lead to a favorable clinical benefit for consensus interferon when compared with the naturally occurring recombinant molecules. Ongoing clinical trials will ascertain whether consensus interferon can be used in a wide array of disease situations, such as chronic viral infections and certain malignancies.

Amino Acid Sequence↗

The use of consensus to develop guidelines for the management of Helicobacter pylori infection in primary care. European Society for Primary Care Gastroenterology.

BACKGROUND: Guidelines are an increasingly important feature of clinical practice and have proliferated over the past decade. When the evidence base for effective practice is limited, guidelines have to derive from the opinions and experience of those with knowledge of the subject. The manner in which a group synthesizes its individual opinions, the consensus process, is central to the validity and applicability of the resulting recommendations. This paper considers the theoretical issues in consensus development and describes the consensus process used in developing the European Society for Primary Care Gastroenterology guidelines for the management of Helicobacter pylori in primary care. METHODS: A consensus development conference of 48 GPs from nine European countries used case scenarios to define clinical management strategies in dyspepsia and H.pylori infection. Structured data collection from this meeting allowed a quantitative measure of the extent of consensus to be produced. RESULTS: Specific recommendations were produced for 15 decision points relevant to the management of H.pylori infection in primary care. DISCUSSION: Consensus development is often utilized in the production of guidelines for clinical practice. Guideline appraisal instruments fail to examine in depth the methods used for this important part of the development process. We describe an approach to consensus development which contains a simple measure of the strength of consensus underlying each recommendation.

Anti-Bacterial Agents↗

A branch point consensus from Arabidopsis found by non-circular analysis allows for better prediction of acceptor sites.

Little knowledge exists about branch points in plants; it has even been claimed that plant introns lack conserved branch point sequences similar to those found in vertebrate introns. A putative branch point consensus sequence for Arabidopsis thaliana resembling the well known metazoan consensus sequence has been proposed, but this is based on search of sequences similar to those in yeast and metazoa. Here we present a novel consensus sequence found by a non-circular approach. A hidden Markov model with a fixed A nucleotide was trained on sequences upstream of the acceptor site. The consensus found by the Markov model shares features with the metazoan consensus, but differs in its details from the consensus proposed earlier. Despite the fact that branch point consensus sequences in plants are weak, we show that a prediction scheme incorporating them leads to a substantial improvement in the recognition of true acceptor sites; the false positive rate being reduced by a factor of 2. We take this as an indication that the consensus found here is the genuine one and that the branch point does play a role in the proper recognition of the acceptor site in plants.

Arabidopsis↗

Delphi based consensus study into planning for chemical incidents.

OBJECTIVE: To achieve consensus in all phases of chemical incident planning and response. DESIGN: A three round Delphi study was conducted using a panel of 39 experts from specialties involved in the management of chemical incidents. Areas that did not reach consensus in the Delphi study were presented as synopsis statements for discussion in four syndicate groups at a conference hosted by the Department of Health Emergency Planning Co-ordination Unit. RESULTS: A total of 183 of 322 statements had reached consensus upon completion of the Delphi study. This represented 56.8% of the total number of statements. Of these, 148 reached consensus at >94% and 35 reached consensus at >89%. The results of the process are presented as a series of synopsis consensus statements that cover all phases of chemical incident planning and response. CONCLUSIONS: The use of a Delphi study and subsequent syndicate group discussions achieved consensus in aspects of all phases of chemical incident planning and response that can be translated into practical guidance for use at regional prehospital and hospital level. Additionally, areas of non-consensus have been identified where further work is required.

Accidents, Occupational↗

Enhancing the stability and folding rate of a repeat protein through the addition of consensus repeats.

Repeat proteins are constructed from a linear array of modular units, giving rise to an overall topology lacking long-range interactions. This suggests that stabilizing repeat modules based on consensus information might be added to a repeat protein domain, allowing it to be extended without altering its overall topology. Here we add consensus modules the ankyrin repeat domain from the Drosophila Notch receptor to investigate the structural tolerance to these modules, the relative thermodynamic stability of these hybrid proteins, and how alterations in the energy landscape influence folding kinetics. Insertions of consensus modules between repeats five and six of the Notch ankyrin domain have little effect on the far and near-UV CD spectra, indicating that neither secondary nor tertiary structure is dramatically altered. Furthermore, stable structure is maintained at increased denaturant concentrations in the polypeptides containing the consensus repeats, indicating that the consensus modules are capable of stabilizing much of the domain. However, insertion of the consensus repeats appears to disrupt cooperativity, producing a two-stage (three-state) unfolding transition in which the C-terminal repeats unfold at moderate urea concentrations. Removing the C-terminal repeats (Notch ankyrin repeats six and seven) restores equilibrium two-state folding and demonstrates that the high stability of the consensus repeats is propagated into the N-terminal, naturally occurring Notch ankyrin repeats. This stability increase greatly increases the folding rate, and suggests that the transition state ensemble may be repositioned in the chimeric consensus-stabilized proteins in response to local stability.

Amino Acid Sequence↗

Rater agreement at lung scintigraphy after consensus training.

PURPOSE: Using the PIOPED criteria in the interpretation of lung scintigraphy, perfect agreement between experienced raters with training in consensus interpretation has been demonstrated. In a previous paper we found a kappa value of 0.54 (0.45-0.63) between experienced raters with no experience of interpretation in consensus; this is significantly lower than the perfect agreement described between consensus-trained raters. The purpose of this study was to reinvestigate the same study population with the same raters, but this time after they had undergone consensus training. MATERIAL AND METHODS: Lung scintigrams of 192 patients were reviewed and categorized according to the PIOPED criteria by 2 raters after consensus training. The 2 raters reviewed a training material of 59 cases, which was not part of the study population, in order to reach a full consensus interpretation. RESULTS: After consensus training the kappa value was 0.57 (0.48-0.66). Three cases had a discrepancy of 2 categories (1.6%), and the remaining discrepancies were of one category. CONCLUSION: Consensus training did not significantly improve the agreement rate between experienced raters from different hospitals. A substantial improvement in agreement rates between hospitals may make heavy demands on resources.

Humans↗