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PubMed2000

From DNA sequence to improved functionality: using protein sequence comparisons to rapidly design a thermostable consensus phytase.

Naturally-occurring phytases having the required level of thermostability for application in animal feeding have not been found in nature thus far. We decided to de novo construct consensus phytases using primary protein sequence comparisons. A consensus enzyme based on 13 fungal phytase sequences had normal catalytic properties, but showed an unexpected 15-22 degrees C increase in unfolding temperature compared with each of its parents. As a first step towards understanding the molecular basis of increased heat resistance, the crystal structure of consensus phytase was determined and compared with that of Aspergillus niger phytase. Aspergillus niger phytase unfolds at much lower temperatures. In most cases, consensus residues were indeed expected, based on comparisons of both three-dimensional structures, to contribute more to phytase stabilization than non-consensus amino acids. For some consensus amino acids, predicted by structural comparisons to destabilize the protein, mutational analysis was performed. Interestingly, these consensus residues in fact increased the unfolding temperature of the consensus phytase. In summary, for fungal phytases apparently an unexpected direct link between protein sequence conservation and protein stability exists.

6-Phytase↗
PubMed2002

The consensus concept for thermostability engineering of proteins: further proof of concept.

Previously, we calculated a consensus amino acid sequence from 13 homologous fungal phytases. A synthetic gene was constructed and recombinantly expressed. Surprisingly, consensus phytase-1 was 15-26 degrees C more thermostable than all parent phytases used in its design [Lehmann et al. (2000)Protein Eng., 13, 49-57]. In the present study, inclusion of six further phytase sequences in the amino acid sequence alignment resulted in the replacement of 38 amino acid residues in either one or both of the new consensus phytases-10 and -11. Since consensus phytase-10, again, was 7.4 degrees C more thermostable than consensus phytase-1, the thermostability effects of most of the 38 amino acid substitutions were tested by site-directed mutagenesis. Both stabilizing and destabilizing mutations were identified, but all affected the stability of the enzyme by <3 degrees C. The combination of all stabilizing amino acid exchanges in a multiple mutant of consensus phytase-1 increased the unfolding temperature from 78.0 to 88.5 degrees C. Likewise, back-mutation of four destabilizing amino acids and introduction of an additional stabilizing amino acid in consensus phytase-10 further increased the unfolding temperature from 85.4 to 90.4 degrees C. The thermostabilization achieved is the result of a combination of slight improvements from multiple amino acid exchanges rather than being the effect of a single or of just a few dominating mutations that have been introduced by chance. The present findings support the general validity of the consensus concept for thermostability engineering of proteins.

6-Phytase↗
PubMed2006

A Delphi-based consensus study into planning for biological incidents.

OBJECTIVE: Biological incidents present a significant threat to health services in the UK. The objective of this study was to achieve consensus in all phases of biological incident planning and response. METHODS: A three-round Delphi study was conducted using a panel of 23 experts from specialities involved in the management of biological incidents. The consensus and non-consensus outcomes from the Delphi study were subsequently presented for discussion in four syndicate groups at a one-day consensus conference funded by the Health Protection Agency. RESULTS: The results of each syndicate group discussion were presented at a subsequent plenary session at the end of the conference. Further iteration of both the consensus and the non-consensus outcomes of the Delphi study resulted in the endorsement, modification, integration or rejection of individual statements. 125 consensus statements were produced. CONCLUSIONS: The 125 synopsis consensus statements that all phases of biological incident planning and response. These can be used to inform policy decisions and translated into practical guidance for emergency planners and first responders at local, regional and national levels.

Accidents, Occupational↗
PubMed1989

Interaction of the H4 autonomously replicating sequence core consensus sequence and its 3'-flanking domain.

Yeast autonomously replicating sequence (ARS) elements are composed of a conserved 11-base-pair (bp) core consensus sequence and a less well defined 3'-flanking region. We have investigated the relationship between the H4 ARS core consensus sequence and its 3'-flanking domain. The minimal sequences necessary and sufficient for function were determined by combining external 3' and 5' deletions to produce a nested set of ARS fragments. Sequences 5' of the core consensus were dispensable for function, but at least 66 bp of 3'-flanking domain DNA was required for full ARS function. The importance of the relative orientation of the core consensus element with respect to the 3'-flanking domain was tested by precisely inverting 14 bp of DNA including the core consensus sequence by oligonucleotide mutagenesis. This core inversion mutant was defective for all ARS function, showing that a fixed relative orientation of the core consensus and 3'-flanking domain is required for function. The 3'-flanking domain of the minimal functional H4 ARS fragment contains three sequences with a 9-of-11-bp match to the core consensus. The role of these near-match sequences was tested by directed mutagenesis. When all near-match sequences with an 8-of-11-bp match or better were simultaneously disrupted by point mutations, the resulting ARS construct retained full replication function. Therefore, multiple copies of a sequence closely related to the core consensus element are not required for H4 ARS function.

Base Sequence↗
PubMed1989

Consensus in patient-therapist interactions. A measure of the therapeutic relationship related to outcome.

This paper discusses consensus between patient and therapist as a measure of the quality of the psychotherapeutic relationship. Consensus is defined by two interpersonal concepts, agreement and understanding, and two intrapersonal concepts, congruency and experienced consensus. 162 patients and their therapists in a Dutch Center for Comprehensive Mental Health Care were rated on the degree of consensus. Two patient self-report outcome measures and one reported by the therapist were related to consensus. The three consensus measures that predicted outcome after 6 months were understanding by the therapist as well as agreement and experienced consensus by the patient. This result suggests that a complementary patient-therapist relationship favors a good psychotherapy result. The instruments in this paper provide a means to measure consensus during the process of psychotherapy. This is a feasible way to both monitor progress and improve the chances of a successful outcome.

Adult↗
PubMed1990

A-type ATP binding consensus sequences are critical for the catalytic activity of the calmodulin-sensitive adenylyl cyclase from Bacillus anthracis.

Analysis of the predicted amino acid sequence of Bacillus anthracis adenylyl cyclase revealed sequences with homology to consensus sequences for A- and B-type ATP binding domains found in many ATP binding proteins. Based on the analysis of nucleotide binding proteins, a conserved basic amino acid residue in the A-type consensus sequence and a conserved acidic amino acid residue in the B-type consensus sequence have been implicated in the binding of ATP. The putative ATP binding sequences in the B. anthracis adenylyl cyclase possess analogous lysine residues at positions 346 and 353 within two A-type consensus sequences and a glutamate residue at position 436 within a B-type consensus sequence. The two A-type consensus sequences overlap each other and have the opposite orientation. To determine whether Lys-346, Lys-353, or Glu-436 of the B. anthracis adenylyl cyclase are crucial for enzyme activity, Lys-346 and Lys-353 were replaced with methionine and Glu-436 with glutamine by oligonucleotide-directed mutagenesis. Furthermore, Lys-346 was also replaced with arginine. The genes encoding the wild type and mutant adenylyl cyclases were placed under the control of the lac promoter for expression in Escherichia coli, and extracts were assayed for adenylyl cyclase activity. In all cases, a 90-kDa polypeptide corresponding to the catalytic subunit of the enzyme was detected in E. coli extracts by rabbit polyclonal antibodies raised against the purified B. anthracis adenylyl cyclase. The proteins with the Lys-346 to methionine or arginine mutations exhibited no adenylyl cyclase activity, indicating that Lys-346 in the A-type ATP binding consensus sequence plays a critical role for enzyme catalysis. Furthermore, the enzyme with the Lys-353 to methionine mutation was also inactive, suggesting that Lys-353 may also directly contribute to enzyme catalysis. In contrast, the protein with the Glu-436 to glutamine mutation retained 75% of enzyme activity, suggesting that Glu-436 in the B-type ATP binding consensus sequence may not be directly involved in enzyme catalysis. It is concluded that Lys-346 and Lys-353 in B. anthracis adenylyl cyclase may interact directly with ATP and contribute to the binding of the nucleotide to the enzyme.

Adenosine Triphosphate↗
PubMed2002

Nkx-2.5 gene induction in mice is mediated by a Smad consensus regulatory region.

In the forming vertebrate heart, bone morphogenetic protein signaling induces expression of the early cardiac regulatory gene nkx-2.5. A similar regulatory interaction has been defined in Drosophila embryos where Dpp signaling mediated by the Smad homologues Mad and Medea directly regulates early cardiac expression of tinman. A conserved cluster of Smad consensus binding sequences was identified in early cardiac regulatory sequences of the mouse nkx-2.5 gene. The importance of the nkx-2.5 Smad consensus region in early cardiac gene expression was examined in transgenic mice and in cultured mouse embryos. In transgenic mice, deletion of the Smad consensus region delays induction of embryonic DeltaSmadnkx-2.5/lacZ gene expression during early heart formation. Induction of DeltaSmadnkx-2.5/lacZ expression is also delayed in the outflow tract myocardium and visceral mesoderm. Targeted mutation of the three Smad consensus sequences inhibited nkx-2.5/lacZ expression in the cardiac crescent, demonstrating a specific requirement for the Smad consensus sites in early cardiac gene induction. Cultured DeltaSmadnkx-2.5/lacZ transgenic mouse embryos also exhibit delayed induction of transgene expression. In the four-chambered heart, deletion of the Smad consensus region resulted in expanded DeltaSmadnkx-2.5/lacZ transgene expression. Thus, the nkx-2.5 Smad consensus region can have positive or negative regulatory function, depending on the developmental context and cellular environment.

Animals↗
PubMed1999

Evaluation of human papillomavirus-consensus primers for HPV detection by the polymerase chain reaction.

Cervical cancer is one of the most frequently found cancers in women and appears to have a viral aetiology. Substantial evidence points to the human papillomaviruses (HPV) as the infectious agents and there is considerable interest in identifying and accurately typing the viruses. Since HPVs now comprise more than 100 different HPV types, the polymerase chain reaction (PCR) has been the preferred methodology for virus identification and typing on isolated DNA. In that context, five commonly employed PCR consensus primers have been evaluated for the detection and typing of HPV. The five consensus primer pairs were derived from the consensus sequences of either the L1 and E1 open reading frames. All primers exhibited approximately equal sensitivity, as defined by the ability to detect HPV DNA, on a series of standard HPV DNA-containing preparations. However, the five primer pairs performed differently on 24 HPV-positive and 34 HPV-negative samples obtained from cervical scrapes which had been typed by type-specific PCR for HPV 6/11, 16, 18 and 33. The values for agreement between identification of samples by a HPV type-specific PCR and the consensus primer PCR were 78, 84, 91, 93 and 98%. Three samples, which were positive with only one of the five consensus primer pairs and were negative with the PCR for HPV types 6/11, 16, 18 and 33, contained other HPV sequences or HPV-related sequences as determined by DNA sequence analysis. To our knowledge, this report represents the first extensive comparison of five different consensus primers in a polymerase chain reaction for the detection of HPV. Our results suggest that PCR typing for human papillomaviruses requires more than one consensus primer pair to identify all HPV-infected samples.

Base Sequence↗
PubMed2004

Canadian 2003 International Consensus Algorithm For the Diagnosis, Therapy, and Management of Hereditary Angioedema.

C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Société d'Angioédème Héréditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near future.

Algorithms↗
PubMed2005

A formal model for consensus and negotiation in environmental management.

Environmental management decisions typically lie at the interface of science and public policy. Consequently, these decisions involve a number of stakeholders with competing agendas and vested interests in the ultimate decision. In such cases, it is appropriate to adopt formal methods for consensus building to ensure transparent and repeatable decisions. In this paper, we use an environmental management case study to demonstrate the utility of a mathematical consensus convergence model in aggregating values (or weights) across groups. Consensus models are applicable when all parties agree to negotiate in order to resolve conflict. The advantage of this method is that it does not require that all members of the group reach agreement, often an impossible task in group decision making. Instead, it uses philosophical foundations in consensus building to aggregate group members' values in a way that guarantees convergence towards a single consensual value that summarizes the group position. We highlight current problems with ad hoc consensus and negotiation methods, provide justification for the adoption of formal consensus convergence models and compare the consensus convergence model with currently used methods for aggregating values across a group in a decision making context. The model provides a simple and transparent decision support tool for group decision making that is straightforward to implement.

Communication↗
PubMed2001

Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders.

OBJECTIVE: Carotid bifurcation angioplasty and stenting (CBAS) has generated controversy and widely divergent opinions about its current therapeutic role. To resolve differences and establish a unified view of CBAS' present role, a consensus conference of 17 experts, world opinion leaders from five countries, was held on November 21, 1999. METHODS: These 17 participants had previously answered 18 key questions on current CBAS issues. At the conference these 18 questions and participants' answers were discussed and in some cases modified to determine points of agreement (consensus), near consensus, (prevailing opinion), or divided opinion (disagreement). RESULTS: Conference discussion added two modified questions, placing a total of 20 key questions before the participants, representing four specialties (interventional radiology, seven; vascular surgery, six; interventional cardiology, three; neurosurgery, one). It is interesting that consensus was reached on the answers to 11 (55%) of 20 of the questions, and near consensus was reached on answers to 6 (30%) of 20 of the questions. Only with the answers to three (15%) of the questions was there persisting controversy. Moreover, both these differences and areas of agreement crossed specialty lines. Consensus Conclusions: CBAS should not currently undergo widespread practice, which should await results of randomized trials. CBAS is currently appropriate treatment for patients at high risk in experienced centers. CBAS is not generally appropriate for patients at low risk. Neurorescue skills should be available if CBAS is performed. When cerebral protection devices are available, they should be used for CBAS. Adequate stents and technology for performing CBAS currently exist. There were divergent opinions regarding the proportions of patients presently acceptable for CBAS treatment (<5% to 100%, mean 44%) and best treated by CBAS (<3% to 100%, mean 34%). These and other consensus conclusions will help physicians in all specialties deal with CBAS in a rational way rather than by being guided by unsubstantiated claims.

Angioplasty↗
PubMed2002

A simulated annealing algorithm for finding consensus sequences.

MOTIVATION: A consensus sequence for a family of related sequences is, as the name suggests, a sequence that captures the features common to most members of the family. Consensus sequences are important in various DNA sequencing applications and are a convenient way to characterize a family of molecules. RESULTS: This paper describes a new algorithm for finding a consensus sequence, using the popular optimization method known as simulated annealing. Unlike the conventional approach of finding a consensus sequence by first forming a multiple sequence alignment, this algorithm searches for a sequence that minimises the sum of pairwise distances to each of the input sequences. The resulting consensus sequence can then be used to induce a multiple sequence alignment. The time required by the algorithm scales linearly with the number of input sequences and quadratically with the length of the consensus sequence. We present results demonstrating the high quality of the consensus sequences and alignments produced by the new algorithm. For comparison, we also present similar results obtained using ClustalW. The new algorithm outperforms ClustalW in many cases.

Algorithms↗
PubMed2006

A consensus process on management of major burns accidents: lessons learned from the café fire in Volendam, The Netherlands.

PURPOSE: The optimum response to the different stages of a major burns incident is still not established. The fire in a café in Volendam on New Year's Eve 2000 was the worst incident in recent Dutch history and resulted in mass burn casualties. The fire has been the subject of several investigations concerned with organisational and medical aspects. Based on the findings in these investigations, a multidisciplinary research group started a consensus study. The aim of this study was to further identify areas of improvement in the care after mass burns incidents. DESIGN/METHODOLOGY/APPROACH: The consensus process comprised three postal rounds (Delphi Method) and a consensus conference (modified nominal group technique). The multidisciplinary panel consisted of 26 Dutch-speaking experts, working in influential positions within the sphere of disaster management and healthcare. FINDINGS: In response to the postal questionnaires, consensus was reached for 66 per cent of the statements. Six topics were subsequently discussed during the consensus conference; three topics were discussed within the plenary session and three during subgroup meetings. During the conference, consensus was reached for seven statements (one subject generated two statements). In total, the panel agreed on 21 statements. These covered the following topics: registration and evaluation of disaster care, capacity planning for disasters, pre hospital care of victims of burns disasters, treatment and transportation priorities, distribution of casualties (including interhospital transports), diagnosis and treatment and education and training. ORIGINALITY/VALUE: In disaster medicine, the paper shows how a consensus process is a suitable tool to identify areas of improvement of care after mass burns incidents.

Adult↗
PubMed1996

Deduced consensus sequence of Sindbis virus strain AR339: mutations contained in laboratory strains which affect cell culture and in vivo phenotypes.

The consensus sequence of the Sindbis virus AR339 isolate, the prototype alphavirus, has been deduced. THe results presented here suggest (i) that a substantial proportion of the sequence divergence evident between the consensus sequence and sequences of laboratory strains of AR339 has resulted from selection for efficient growth in cell culture, (ii) that many of these changes affect the virulence of the virus in animal models, and (iii) that such modified genetic backgrounds present in laboratory strains can exert a significant influence on genetic studies of virus pathogenesis and host range. A laboratory strain of Sindbis virus AR339 was sequenced and cloned as a cDNA (pTRSB) from which infectious virus (TRSB) could be derived. The consensus sequence was deduced from the complete sequences of pTRSB and HRsp (E. G. Strauss, C. M. Rice, and J. H. Strauss, Virology 133:92-110, 1984), from partial sequences of the glycoprotein genes of three other AR339 laboratory strains, and by comparison with the sequences of the glycoprotein genes of three other AR339 sequence. HRsp differed form the consensus sequence by eight coding changes, and TRSB differed by three coding changes. In the 5' untranslated region, HRsp differed from the consensus sequence at nucleotide (nt) 5. These differences were likely the result of cell culture passage of the original AR339 isolate. At three of the difference loci (one in TRSB and two in HRsp), selection of cell-culture-adaptive mutations was documented with Sindbis virus or other alphaviruses. Selection in cell culture often results in attenuation of virulence in animals. Considering the TRSB and HRsp sequences together, one noncoding difference from the consensus (an A-for-G substitution in the 5' untranslated region at nt 5) and six coding differences in the glycoprotein genes (at E2 amino acids 1, 3, 70, and 172 and at E1 amino acids 72 and 237) were at loci which, either individually or in combination, significantly affected alphavirus virulence in mice. Although the levels of virulence of isogenic strains containing either nt 5 A or nt 5 G did not differ significantly in neonatal mice, the presence of nt 5 A greatly enhanced the effect of a second attenuating mutation in the E2 gene. These results suggest that minimal differences in the "wild type" genetic background into which an additional mutation is introduced can have a dramatic effect on apparent virulence and pathogenesis phenotypes. A cDNA clone of the consensus AR339 sequence, a sequence devoid of occult attenuating mutations introduced by cell culture passage, will allow the molecular genetic examination of cell culture and in vivo phenotypes of a virus which may best reflect the sequence of Sindbis virus AR339 at the time of its isolation.

Alphavirus Infections↗
PubMed2002

Human immunodeficiency virus type 1 subtype C molecular phylogeny: consensus sequence for an AIDS vaccine design?

An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence of HIV-1C infection in the southern African countries and with an expanding epidemic in India and China. Understanding the molecular phylogeny and genetic diversity of HIV-1C viruses may be important for the design and evaluation of an HIV vaccine for ultimate use in the developing world. In this study we analyzed the phylogenetic relationships (i) between 73 non-recombinant HIV-1C near-full-length genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C consensus sequences that represent different geographic subsets; and (iii) between specific isolates and consensus sequences. Based on the phylogenetic analyses of 73 near-full-length genomes, 16 "lineages" (a term that is used hereafter for discussion purposes and does not imply taxonomic standing) were identified within HIV-1C. The lineages were supported by high bootstrap values in maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum-likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to 7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence were significantly lower than distances between samples within all HIV-1C proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid frequencies were presented (that of Gag is presented in this work; those of Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm]). Additionally, in the promoter region three NF-kappa B sites (GGGRNNYYCC) were identified within the consensus sequences of the entire set or any subset of HIV-1C isolates. This study suggests that the consensus sequence approach could overcome the high genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly if the assumption that an HIV-1C antigen with a more extensive match to the circulating viruses is likely to be more efficacious is proven in efficacy trials.

AIDS Vaccines↗
PubMed1995

Interaction of p53 with its consensus DNA-binding site.

We have analyzed the specific interaction of murine p53 with the consensus DNA-binding sequence 5'-AGACATGCCT-AGACATGCCT-3'. We used segments of p53 lacking the C-terminal, nonspecific DNA-binding domain because the presence of an autonomous nonspecific DNA-binding domain in wild-type p53 would complicate analysis of site-specific DNA binding. p53 amino acids 1 to 360 bind the consensus sequence as tetramers, and DNA binding promotes tetramer-tetramer interactions. p53 amino acids 80 to 290, lacking both the nonspecific DNA-binding and tetramerization domains, consistently bind consensus DNA as four monomers and only as four monomers. The virtual absence of stable binding by fewer than four monomers, even at low concentrations of p53, argues that binding by amino acids 80 to 290 is strongly cooperative. Because p53 tetramers and monomers do not simultaneously bind a single DNA consensus sequence, we conclude that a single tetramer of wild-type p53 engages the recognition sequences of the entire DNA consensus site. We further show that consensus DNA consists of two functional half-sites. Insertions, deletions, or rearrangements within the half-sites reduce DNA binding dramatically. In contrast, two half-sites separated by insertions bind p53 relatively efficiently. Insertions that place half-sites on opposite faces of the DNA helix reduce DNA binding more than insertions that place half-sites on the same face of the helix. Transcription studies, in vivo, strongly confirm the rotational specificity of the p53 interaction with consensus DNA. The ability of single p53 tetramers to bind separated DNA half-sites argues that p53 has a flexible tetramerization region.

Animals↗
PubMedDate not supplied

Once-daily antiretroviral therapies for HIV infection: Consensus Statement of an Advisory Committee of the International Association of Physicians in AIDS Care.

OBJECTIVE: Adherence is essential to successful virologic outcome of highly active antiretroviral therapy (HAART). Documented factors contributing to poor adherence include toxicity, food requirements, and pill burden. Once-daily antiretroviral therapies for HIV infection offer potential benefit by decreasing pill burden and dosing frequency, which may subsequently improve treatment adherence. This Consensus Statement is intended to offer guidance to physicians actively involved in HIV/AIDS care. PARTICIPANTS: Eight physicians with expertise in HIV medicine were invited by the International Association of Physicians in AIDS Care (IAPAC) to serve on an ad hoc Advisory Committee. CONSENSUS PROCESS: IAPAC convened the Advisory Committee in June 2002 to develop a draft Consensus Statement. Scientific and clinical research, and other data in published literature and abstracts from scientific conferences were considered by strength of evidence. A Subcommittee updated the Consensus Statement in October 2002 to reflect relevant data presented at the XIV International AIDS Conference and the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. This document represents consensus agreement of the Advisory Committee. CONFLICT OF INTEREST DISCLOSURE: The International Association of Physicians in AIDS Care sponsored and coordinated the development of this Consensus Statement with an unrestricted educational grant from Bristol-Myers Squibb. The opinions expressed in this Consensus Statement represent only those of the Advisory Committee.

Anti-Retroviral Agents↗
PubMed2004

Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.

INTRODUCTION: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. METHODS: We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. RESULTS: We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at http://www.ADQI.net) CONCLUSION: Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology.

Acute Kidney Injury↗