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PubMed2006

Consensus by democracy. Using meta-analyses of microarray and genomic data to model the cold acclimation signaling pathway in Arabidopsis.

The whole-genome response of Arabidopsis (Arabidopsis thaliana) exposed to different types and durations of abiotic stress has now been described by a wealth of publicly available microarray data. When combined with studies of how gene expression is affected in mutant and transgenic Arabidopsis with altered ability to transduce the low temperature signal, these data can be used to test the interactions between various low temperature-associated transcription factors and their regulons. We quantized a collection of Affymetrix microarray data so that each gene in a particular regulon could vote on whether a cis-element found in its promoter conferred induction (+1), repression (-1), or no transcriptional change (0) during cold stress. By statistically comparing these election results with the voting behavior of all genes on the same gene chip, we verified the bioactivity of novel cis-elements and defined whether they were inductive or repressive. Using in silico mutagenesis we identified functional binding consensus variants for the transcription factors studied. Our results suggest that the previously identified ICEr1 (induction of CBF expression region 1) consensus does not correlate with cold gene induction, while the ICEr3/ICEr4 consensuses identified using our algorithms are present in regulons of genes that were induced coordinate with observed ICE1 transcript accumulation and temporally preceding genes containing the dehydration response element. Statistical analysis of overlap and cis-element enrichment in the ICE1, CBF2, ZAT12, HOS9, and PHYA regulons enabled us to construct a regulatory network supported by multiple lines of evidence that can be used for future hypothesis testing.

Acclimatization↗
PubMed2003

A consensus view of fold space: combining SCOP, CATH, and the Dali Domain Dictionary.

We have determined consensus protein-fold classifications on the basis of three classification methods, SCOP, CATH, and Dali. These classifications make use of different methods of defining and categorizing protein folds that lead to different views of protein-fold space. Pairwise comparisons of domains on the basis of their fold classifications show that much of the disagreement between the classification systems is due to differing domain definitions rather than assigning the same domain to different folds. However, there are significant differences in the fold assignments between the three systems. These remaining differences can be explained primarily in terms of the breadth of the fold classifications. Many structures may be defined as having one fold in one system, whereas far fewer are defined as having the analogous fold in another system. By comparing these folds for a nonredundant set of proteins, the consensus method breaks up broad fold classifications and combines restrictive fold classifications into metafolds, creating, in effect, an averaged view of fold space. This averaged view requires that the structural similarities between proteins having the same metafold be recognized by multiple classification systems. Thus, the consensus map is useful for researchers looking for fold similarities that are relatively independent of the method used to compare proteins. The 30 most populated metafolds, representing the folds of about half of a nonredundant subset of the PDB, are presented here. The full list of metafolds is presented on the Web.

Amino Acid Motifs↗
PubMed1991

Recognition of the folding consensus in RNA secondary structures by the topological-filtering method.

Functionally homologous RNA sequences can substantially diverge in their primary sequences but it can be reasonably assumed that they are related in their higher-degree structures. The problem to find such structures and simultaneously satisfy as far as possible the free-energy-minimization criterion, is considered here in two aspects. Firstly a quantitative measure of the folding consensus among secondary structures is defined, translating each structure into a linear representation and using the correlation theorem to compare them. Secondly an algorithm for the parallel search for secondary structures according to the free-energy-minimization criterion, but with a filtering action on the basis of the folding consensus measure is presented. The method is tested on groups of RNA sequences different in origin and in functions, for which proposals of homologous secondary structures based on experimental data exist. A comparison of the results with a blank consisting of a search on the basis of the free energy minimization alone is always performed. In these tests the method shows its ability in obtaining, from different sequences, secondary structures characterized by a high-folding consensus measure also when lower free energy but not homologous structures are possible. Two applications are also shown. The first demonstrates the transfer of experimental data available for one sequence, to a functionally related and therefore homologous one. The second application is the possibility of using a topological probe in the search for precise structural motifs.

Algorithms↗
PubMed1993

Consensus, self-other agreement, and accuracy in personality judgment: an introduction.

Consensus in personality judgment refers to the agreement with which two people (or more) can describe the personality of another; self-other agreement refers to the similarity between personality descriptions by the self and by others; and accuracy refers to the degree to which personality descriptions capture real attributes of the persons described. After years of focusing on other subjects, researchers recently have renewed their interest in these three topics. Current empirical research is philosophically diverse and includes studies incorporating pragmatic, constructivist, and realist approaches. Other research is resolving long-standing methodological problems and providing new analytic techniques for the study of consensus, self-other agreement, and accuracy. This special issue includes articles exemplifying all of these research approaches and documents that a new wave of research on consensus, self-other agreement, and accuracy in personality judgment now comprises a burgeoning field that has finally come of age.

Humans↗
PubMed1993

Analyzing consensus in personality judgments: a variance components approach.

Although peer raters of personality traits do tend to agree, the strength of their consensus is often modest. This article focuses on methods for analyzing determinants of consensus. Variance components methods adapted from generalizability theory have some untapped potential for understanding gradations in consensus. The methods allow explicit analysis of how social categories of targets might affect judgments of raters from the same or different social categories. Limitations of the variance components approach are also discussed. The methods are illustrated with artificial data.

Humans↗
PubMed1985

lac Up-promoter mutants with increased homology to the consensus promoter sequence.

Four lac promoter mutants were constructed. The mutations increased the homology between the lac promoter and the consensus promoter sequences by introducing the consensus -10 and -35 regions and the consensus spacing of 17 residues between these two regions. The promoter mutants were cloned into a pBR322-derivatized vector upstream from the lacZ gene, and levels of beta-galactosidase were an indication of promoter activity. All mutants exhibited higher activity than did the wild-type promoter.

Base Sequence↗
PubMed2004

Comparison of oligonucleotide ligation assay and consensus sequencing for detection of drug-resistant mutants of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and plasma.

Drug-resistant mutants of human immunodeficiency virus type 1 (HIV-1) recede below the limit of detection of most assays applied to plasma when selective pressure is altered due to changes in antiretroviral treatment (ART). Viral variants with different mutations are selected by the new ART when replication is not suppressed or wild-type variants with greater replication fitness outgrow mutants following the cessation of ART. Mutants selected by past ART appear to persist in reservoirs even when not detected in the plasma, and when conferring cross-resistance they can compromise the efficacy of novel ART. Oligonucleotide ligation assay (OLA) of virus in plasma and peripheral blood mononuclear cells (PBMC) was compared to consensus sequence dideoxynucleotide chain terminator sequencing for detection of 91 drug resistance mutations that had receded below the limit of detection by sequencing of plasma. OLA of plasma virus detected 27.5% (95% confidence interval [CI], 19 to 39%) of mutant genotypes; consensus sequencing of the PBMC amplicon from the same specimen detected 23.1% (95% CI, 14 to 34%); and OLA of PBMC detected 53.8% (95% CI, 44 to 64%). These data suggest that concentrations of drug-resistant mutants were greater in PBMC than in plasma after changes in ART and indicate that the OLA was more sensitive than consensus sequencing in detecting low levels of select drug-resistant mutants.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cyclic amplification and selection of targets (CASTing) for the myogenin consensus binding site.

The consensus binding site for the muscle regulatory factor myogenin was determined from an unbiased set of degenerate oligonucleotides using CASTing (cyclic amplification and selection of targets). Stretches of totally random sequence flanked by polymerase chain reaction priming sequences were mixed with purified myogenin or myotube nuclear extracts, DNA-protein complexes were immunoprecipitated with an antimyogenin antibody, and the DNA was amplified by polymerase chain reaction. Specific binding was obtained after four to six cycles of CASTing. The population of selected binding sites was then cloned, and a consensus was determined from sequencing individual isolates. Starting from a pool with 14 random bases, purified myogenin yielded a consensus binding site of AACAG[T/C]TGTT, while nuclear extracts retrieved the sequence TTGCACCTGTTNNTT from a pool containing 35 random bases. The latter sequence is consistent with that predicted from combining an E12/E47 half-site (N[not T]CAC) with the purified myogenin half-site ([T/C] TGTT). The presence of paired E boxes in many of the sequences isolated following CASTing with nuclear extracts proves that myogenin can bind cooperatively with other E-box-binding factors.

Animals↗
PubMed1986

A consensus sequence polymer inhibits in vivo expression of heat shock genes.

Promoter function for hsp70 gene expression in Drosophila melanogaster was studied with an in vivo competition assay. A polymer of 40 tandem copies of the pair of regulatory elements of the hsp70 gene was constructed and cloned into a plasmid vector. Various marked genes were cotransfected with the polymer plasmid into Schneider line 2 cells, and their expression was determined by enzyme activity measurements. The polymer dramatically inhibited expression of cotransfected hsp70, hsp26, and hsp83 genes, but not cotransfected copia and histone genes. Our results indicate that in vivo, a trans-acting, positive regulatory factor, which can be titrated by heat shock consensus sequences, is required for activation of heat shock genes and is specific for these genes; the coordinate induction of different heat shock genes appears to be mediated by similar, but not identical, interactions of the trans-acting induction factor and the cis-acting heat shock consensus sequences; and the uninduced or basal level expression of the transfected hsp70 gene is also due to interaction of the consensus sequence with a positively acting factor.

Acetyltransferases↗
PubMed2006

Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies.

BACKGROUND: The classification of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) for epidemiology studies is confusing. The existing schemes such as American College of Rheumatology (ACR) criteria, Chapel Hill Consensus Conference (CHCC) definitions and Lanham criteria produce overlapping and conflicting classifications, making it difficult to compare incidence figures. AIM: To develop a consensus method of using these criteria and definitions for epidemiological studies to permit comparison without confounding by classification. METHODS: A stepwise algorithm was developed by consensus between a group of doctors interested in the epidemiology of vasculitis. The aim was to categorise patients with Wegener's granulomatosis, microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and PAN into single clinically relevant categories. The ACR and Lanham criteria for CSS, and ACR criteria for Wegener's granulomatosis were applied first, as these were considered to be the most specific. Surrogate markers for Wegener's granulomatosis were included to distinguish Wegener's granulomatosis from MPA. MPA was classified using the CHCC definition and surrogate markers for renal vasculitis. Finally, PAN was classified using the CHCC definition. The algorithm was validated by application to 20 cases from each centre and 99 from a single centre, followed by a paper case exercise. RESULTS: A four-step algorithm was devised. It successfully categorises patients into a single classification. There was good correlation between observers in the paper case exercise (91.5%; unweighted kappa = 0.886). CONCLUSION: The algorithm achieves its aim of reliably classifying patients into a single category. The use of the algorithm in epidemiology studies should permit comparison between geographical areas.

Algorithms↗
PubMed2002

Delphi type methodology to develop consensus on the future design of EMS systems in the United Kingdom.

OBJECTIVE: To develop consensus opinion on future design characteristics of Emergency Medical Services (EMS) systems in the UK with particular regard to advanced life support skills (ALS). DESIGN: A Delphi questionnaire design with two rounds to gain a consensus of opinion. Investigation of four aspects of EMS design is reported-type of response to a priority based dispatch category, transportation options, enhancement of paramedic skills, and structure of a first responder system. SUBJECTS: Chief executives, directors of operations, and medical directors of Ambulance Trusts in the United Kingdom. OUTCOME MEASURES: Likert scales (0-9) to score opinion on a series of statements with achievement of inter-round consistency. A median score of 0-4 was classified as disagreement and 6-9 as agreement. RESULTS: A 65% response to the first questionnaire and with iteration, 52% response to the second questionnaire was attained. A tiered response (paramedics, technicians, and basic life support first responders) with technicians responding to selected category A and B calls and all category C calls (median score (MS) 7.5, interquartile range (IQR) 4), was recommended. Inter-unit handover of selected calls to maintain paramedic availablity ( MS 7.5, IQR 3.75) and enhancement of paramedic skills (MS 7.0, IQR 4.0) was also proposed. Finally, the development of a first responder system fully integrated into the EMS (MS 8.0, IQR 2.75) involving other agencies including the police force, fire service, and trained members of the local community was agreed. CONCLUSIONS: Senior expert staff from Ambulance Trusts in the UK achieved consensus on certain design characteristics of EMS systems. These are significantly different from the present EMS model.

Administrative Personnel↗
PubMed2005

Making psychological theory useful for implementing evidence based practice: a consensus approach.

BACKGROUND: Evidence-based guidelines are often not implemented effectively with the result that best health outcomes are not achieved. This may be due to a lack of theoretical understanding of the processes involved in changing the behaviour of healthcare professionals. This paper reports the development of a consensus on a theoretical framework that could be used in implementation research. The objectives were to identify an agreed set of key theoretical constructs for use in (1) studying the implementation of evidence based practice and (2) developing strategies for effective implementation, and to communicate these constructs to an interdisciplinary audience. METHODS: Six phases of work were conducted to develop a consensus: (1) identifying theoretical constructs; (2) simplifying into construct domains; (3) evaluating the importance of the construct domains; (4) interdisciplinary evaluation; (5) validating the domain list; and (6) piloting interview questions. The contributors were a "psychological theory" group (n = 18), a "health services research" group (n = 13), and a "health psychology" group (n = 30). RESULTS: Twelve domains were identified to explain behaviour change: (1) knowledge, (2) skills, (3) social/professional role and identity, (4) beliefs about capabilities, (5) beliefs about consequences, (6) motivation and goals, (7) memory, attention and decision processes, (8) environmental context and resources, (9) social influences, (10) emotion regulation, (11) behavioural regulation, and (12) nature of the behaviour. CONCLUSIONS: A set of behaviour change domains agreed by a consensus of experts is available for use in implementation research. Applications of this domain list will enhance understanding of the behaviour change processes inherent in implementation of evidence-based practice and will also test the validity of these proposed domains.

Evidence-Based Medicine↗
PubMed2005

Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites.

Transfection studies using mutant constructs have implicated one or both protein kinase A (PKA) consensus phosphorylation sites [serines 552 and 605 in rat Na(+)/H(+) exchanger type 3 (NHE3)] as critical for mediating inhibition of NHE3 in response to several stimuli including dopamine. However, whether one or both of these sites is actually phosphorylated in endogenous NHE3 in proximal tubule cells is unknown. The purpose of this study was to generate phosphospecific antibodies so that the state of phosphorylation of these serine residues in endogenous NHE3 could be assessed in vitro and in vivo. To this end, polyclonal and monoclonal phosphospecific peptide antibodies were generated against each PKA consensus site. Phosphospecificity was established by ELISA and Western blot assays. We then used these antibodies in vitro to evaluate the effect of dopamine on phosphorylation of the corresponding PKA sites (serines 560 and 613) in NHE3 endogenously expressed in opossum kidney cells. Baseline phosphorylation of both sites was detected that was significantly increased by dopamine. Next, we determined the baseline phosphorylation state of each serine in rat kidney NHE3 in vivo. We found that serine 552 of NHE3 is phosphorylated to a much greater extent than serine 605 at baseline in vivo. Moreover, we detected a distinct subcellular localization for NHE3 phosphorylated at serine 552 compared with total NHE3. Specifically, NHE3 phosphorylated at serine 552 localized to the coated pit region of the brush-border membrane, where NHE3 is inactive, while total NHE3 was found throughout the brush-border membrane. These findings strongly suggest that phosphorylation of NHE3 plays a role in its subcellular trafficking in vivo. In conclusion, we successfully generated phosphospecific antibodies that should be useful to assess the phosphorylation of endogenous NHE3 at its two PKA consensus sites under a variety of physiological conditions in vitro and in vivo.

Animals↗
PubMed2005

Report on the Dutch consensus development meeting for implementation and further development of population screening for colorectal cancer based on FOBT.

A consensus development meeting was held to evaluate whether or not in the Netherlands all requirements were fulfilled for implementation of population screening with FOBT for colorectal cancer, or whether consensus was present that fulfilment by additional research or organisational actions could be obtained within 2-3 years. There was consensus that all classical Wilson and Jungner (1968) criteria, and six additional ones added more recently, had already been fulfilled or could be fulfilled within 2-3 years. Consequently, it was concluded that a national population screening for colorectal cancer should be implemented and carried out in the Netherlands in line with current national and European cancer screening programmes. A list of organisational actions to be taken was established. Research that is needed before the actual national launch of the screening within 2-3 years has been defined. Priorities have to be set for research and organisational actions for the coming 2-3 years for the implementation of population screening. In addition, research suggestions have been defined for the next 10-15 years for evaluation and/or improvement of implemented FOBT screening, and for future screening methodology. It was considered essential that infrastructure for future research would be embedded in the screening programme. A project group to arrange this should be formed.

Adenoma↗
PubMed2004

Mannheim intima-media thickness consensus.

Intima-media thickness (IMT) is increasingly used in clinical trials as a surrogate end point for determining the success of interventions that lower risk factors for atherosclerosis. The necessity for unified criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is addressed in this consensus statement. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness of > or =1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is recommended in all epidemiological and interventional trials dealing with vascular diseases to improve characterization of the population investigated. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from few exceptions. Although IMT has been suggested to represent an important risk marker, it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of studies incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

Arteriosclerosis↗
PubMed1982

Scoring patient management problems: external validation of expert consensus.

This study determined the extent to which medical faculty agreed when rating options in two written patient management problems in diabetes mellitus. Another purpose was to determine whether option weights (used for scoring) based on the consensus ratings of faculty actually predict the choices of well-qualified physicians. Experts showed better-than-chance agreement but with considerable variation from one part of a problem to another (31% to 73%). Nevertheless, consensus ratings were very accurate predictors of the decisions of endocrinology fellows (correlations from .60 to .97). When scoring weights are assigned to options in patient management problems, consensus (average) ratings of experts are likely to demonstrate high concurrent validity for well-qualified clinicans.

Adult↗
PubMedDate not supplied

Assessing rater performance without a "gold standard" using consensus theory.

This study illustrates the use of consensus theory to assess the diagnostic performances of raters and to estimate case diagnoses in the absence of a criterion or "gold" standard. A description is provided of how consensus theory "pools" information provided by raters, estimating rater competencies and differentially weighting their responses. Although the model assumes that raters respond without bias (i.e., sensitivity = specificity), a Monte Carlo simulation with 1,200 data sets shows that model estimates appear to be robust even with bias. The model is illustrated on a set of elbow radiographs, and consensus-model estimates are compared with those obtained from follow-up data. Results indicate that with high rater competencies, the model retrieves accurate estimates of competency and case diagnoses even when raters' responses are biased.

Adult↗
PubMed1996

Clinical evaluation of global change in Alzheimer's disease: identifying consensus.

It is important that clinicians who rate global change as part of Alzheimer's disease (AD) clinical drug trials agree on a relevant set of behaviors and information to be considered in formulating their rating. Yet, consensus among raters has been difficult to establish, and inter-rater reliability of clinical global impression of change (CGIC) ratings has been low. In preparation for the development of a new CGIC scale to be used in AD clinical trials, the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), we surveyed clinicians at sites comprising the National Institute on Aging-sponsored ADCS participating centers to identify whether or not consensus regarding CGICs exists. Overall, respondents reported that a CGIC should include an assessment of the patient's function and mental status, a care giver interview, and a standardized set of questions, and it should take approximately 20 minutes per interview. Depending on a patient's level of impairment, raters consider different areas of behavior in formulating a CGIC rating. These findings demonstrate the considerable consensus regarding the CGIC rating process, and were integrated into the design of the ADCS-CGIC, currently in use.

Alzheimer Disease↗