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Coding rules for amino acids in the genetic code: the genetic code is a minimal code of mutational deterioration.

Coding rules for amino acids in the genetic code are discussed from the point that the genetic code is a minimal code of mutational deterioration. The global mutational deterioration (GMD) function is defined through several parameters describing single base mutations and amino acid distances. The problem of searching for the global minimum of the GMD function is discussed in some detail. From GMD minimization under initial constraints we have succeeded in deducing the standard genetic code.

Amino Acids↗

Arrangement of coding and non-coding sequences in the DNA molecules coding for rRNAs in Oxytricha sp. DNA of ciliated protozoa. VII.

All of the genes in the macronucleus of Oxytricha sp. occur on physically separate "gene-sized" DNA molecules. We have inserted the DNA molecule that codes for rRNA into a bacterial plasmid in order to study its structure and function. Using restriction nuclease mapping and hybridization of 125I-rRNAs to gel separated DNA fragments we have determined that the intact rDNA is 8,140+/-50 base pairs (bp) in length. Reading from one end, the molecule consists of approximately 1,540 bp of non-coding DNA, approximately 2,100+/-50 bp that code for 19S rRNA, approximately 3,700+/-50 bp that code for 25 rTNA, and approximately 620+/-50 bp of non-coding DNDA. The 5.8S rRNA coding sequence (approximately 150 bp) occurs at one end of the 25S RNA coding region but which end is not known yet. All three rRNAs are encoded in the same strand of the DNA molecule, and transcription is in the order: 19S leads to 25S.

Animals↗

Phylogenetics of asterids based on 3 coding and 3 non-coding chloroplast DNA markers and the utility of non-coding DNA at higher taxonomic levels.

Asterids comprise 1/4-1/3 of all flowering plants and are classified in 10 orders and >100 families. The phylogeny of asterids is here explored with jackknife parsimony analysis of chloroplast DNA from 132 genera representing 103 families and all higher groups of asterids. Six different markers were used, three of the markers represent protein coding genes, rbcL, ndhF, and matK, and three other represent non-coding DNA; a region including trnL exons and the intron and intergenic spacers between trnT (UGU) to trnF (GAA); another region including trnV exons and intron, trnM and intergenic spacers between trnV (UAC) and atpE, and the rps16 intron. The three non-coding markers proved almost equally useful as the three coding genes in phylogenetic reconstruction at the high level of orders and families in asterids, and in relation to the number of aligned positions the non-coding markers were even more effective. Basal interrelationships among Cornales, Ericales, lamiids (new name replacing euasterids I), and campanulids (new name replacing euasterids II) are resolved with strong support. Family interrelationships are fully or almost fully resolved with medium to strong support in Cornales, Garryales, Gentianales, Solanales, Aquifoliales, Apiales, and Dipsacales. Within the three large orders Ericales, Lamiales, and Asterales, family interrelationships remain partly unclear. The analysis has contributed to reclassification of several families, e.g., Tetrameristaceae, Ebenaceae, Styracaceae, Montiniaceae, Orobanchaceae, and Scrophulariaceae (by inclusion of Pellicieraceae, Lissocarpaceae, Halesiaceae, Kaliphoraceae, Cyclocheilaceae, and Myoporaceae+Buddlejaceae, respectively), and to the placement of families that were unplaced in the APG-system, e.g., Sladeniaceae, Pentaphylacaceae, Plocospermataceae, Cardiopteridaceae, and Adoxaceae (in Ericales, Ericales, Lamiales, Aquifoliales, and Dipsacales, respectively), and Paracryphiaceae among campanulids. Several families of euasterids remain unclassified to order.

Chloroplasts↗

Accuracy of ICD-9-CM coding for the identification of patients with acute ischemic stroke: effect of modifier codes.

BACKGROUND AND PURPOSE: Discharge ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes have been used to identify patients with acute stroke for epidemiological, quality of care, and cost studies. The aim of this study was to determine if the accuracy of the primary ICD-9-CM codes for ischemic stroke is improved by modifier codes and how specific codes reflect stroke subtype diagnoses. METHODS: Available hospital charts for all patients discharged from a single hospital between May 1995 and June 1997 with ICD-9-CM codes 433 (occlusion and stenosis of precerebral arteries), 434 (occlusion of cerebral arteries), or 436 (acute but ill-defined cerebrovascular disease) listed in the first position were reviewed. The primary discharge diagnosis was verified, and a presumed stroke subtype was assigned on the basis of information provided in the medical record. RESULTS: Charts were available for 175 of the 198 identified patients (88%). Of these, 61% had an acute ischemic stroke (code 433, 4%; 434, 82%; 436, 79%) with the remaining patients having other conditions. Of the 130 patients with a modifier code indicating cerebral infarction, 79% had an acute stroke; of the 45 patients with a modifier code indicating an absence of cerebral infarction, 7% had acute stroke (sensitivity, 0.97; specificity, 0.60). The codes with the highest proportions of ischemic stroke cases were 434.11 (embolic occlusion of cerebral arteries with infarction, 85%), 434.91 (unspecified occlusion of precerebral arteries with infarction, 82%), and 436 (79%), with a combined sensitivity of 0.81 and specificity of 0.90. On review, 73% of patients with code 434.11 had embolic strokes, and 47% of those with code 436 had an identified stroke cause. Of patients with code 434.91, 39% had stroke of uncertain cause, 25% "lacunar," 17% atherothrombosis, and 15% embolism. CONCLUSIONS: Despite the use of modifier codes, 15% to 20% of patients with the indicated primary ICD-9-CM codes have conditions other than acute ischemic stroke. Although the proportion of patients with acute stroke increased from 61% to 79% with the use of modifier codes, the inclusion of modifier codes did not have an appreciable effect on the accuracy of the coding if patients with code 433 are excluded. Assignment of presumed ischemic stroke subtype is particularly inaccurate.

Acute Disease↗

Using SNOMED CT codes for coding information in electronic health records for stroke patients.

For a project on development of an Electronic Health Record (EHR) for stroke patients, medical information was organised in care information models (templates). All (medical) concepts in these templates need a unique code to make electronic information exchange between different EHR systems possible. When no unique code could be found in an existing coding system, a code was made up. In the study presented in this article we describe our search for unique codes in SNOMED CT to replace the self made codes. This to enhance interoperability by using standardized codes. We wanted to know for how many of the (self made) codes we could find a SNOMED CT code. Next to that we were interested in a possible difference between templates with individual concepts and concepts being part of (scientific) scales. Results of this study were that we could find a SNOMED CT code for 58% of the concepts. When we look at the concepts with a self made code, 54.9% of these codes could be replaced with a SNOMED CT code. A difference could be detected between templates with individual concepts and templates that represent a scientific scale or measurement instrument. For 68% of the individual concepts a SNOMED CT could be found. However, for the scientific scales only 26% of the concepts could get a SNOMED CT code. Although the percentage of SNOMED CT codes found is lower than expected, we still think SNOMED CT could be a useful coding system for the concepts necessary for the continuity of care for stroke patients, and the inclusion in Electronic Health Records. Partly this is due to the fact that SNOMED CT has the option to request unique codes for new concepts, and is currently working on scale representation.

Forms and Records Control↗

Reliability of report coding of hospital referrals in primary care versus practice-based coding.

Coding of medical data according to a suitable classification is useful to epidemiological research in primary care but its implementation at practice-based level may be considered as extra work by participating practitioners. Secondary coding from reported data can be considered as a possible alternative to practice-based coding. The purpose of this study was to assess the inter-rater reliability of report coding versus practice-based coding of morbidity data. Via teleinformatics, 300 French general practitioners from the French Sentinel epidemiological network transmitted in free text, on a continuous real-time basis, the health problems generating each hospital referral they made since August 1997. All these reports were centrally coded according to the International Classification of Primary Care (ICPC). A subsample of 120 reports were coded in local practices for comparison. Codes resulting from blind centralized free-text coding were compared with practice-based codes. For the 120 referrals reported, the K measure of agreement for the number of codes was 0.65 (95% confidence interval [CI], CI: 0.52-0.77), and for the chapters selected, 0.84 (95% CI: 0.78-0.91). Discrepancies attributable to the centralized coding only occurred for 7.5% of the referrals, and were due to the lack of specificity of the information transmitted as free text. A thesaurus of correspondences between problem(s) generating referrals and ICPC codes was built from 5000 referrals, and has been used routinely for the automated report coding of an additional sample of 1691 referrals. We conclude that centralized coding is a reliable alternative to practice-based coding in primary care, provided that physicians give sufficiently specific information.

Classification↗

The composition of coding joints formed in V(D)J recombination is strongly affected by the nucleotide sequence of the coding ends and their relationship to the recombination signal sequences.

V(D)J recombination proceeds in two stages. Precise cleavage at the border of the conserved recombination signal sequences (RSSs) and the coding ends results in flush double-stranded signal ends and coding ends terminating in hairpins. In the second stage, the signal and coding ends are processed into signal and coding joints. Coding ends containing certain nucleotide homopolymers affect the efficiency of V(D)J recombination. In this study, we have tested the effect of small changes in coding-end nucleotide composition on the frequency of coding- and signal joint formation. Furthermore, we have determined the sequences of coding joints resulting from recombination of coding ends with different compositions. We found that the presence of two T nucleotides 5' of both RSSs, but not a single T, reduces the frequency of signal joint formation, i.e., interferes with the cleavage stage of V(D)J recombination. However, coding-joint processing is sensitive even to a single T. Both the sequence of the coding ends and the particular RSS (12-mer or 23-mer) with which the coding end is associated affect the final composition of the coding joints. Thus, the presence of P nucleotides, the conservation of one undeleted coding end, the formation of joints without any deletions, and the template-dependent insertion of nucleotides are strongly influenced by the coding-end nucleotide composition and/or RSS association. The implications of these results with respect to the processing of coding ends are discussed.

Animals↗

Phase II evaluation of clinical coding schemes: completeness, taxonomy, mapping, definitions, and clarity. CPRI Work Group on Codes and Structures.

OBJECTIVE: To compare three potential sources of controlled clinical terminology (READ codes version 3.1, SNOMED International, and Unified Medical Language System (UMLS) version 1.6) relative to attributes of completeness, clinical taxonomy, administrative mapping, term definitions and clarity (duplicate coding rate). METHODS: The authors assembled 1929 source concept records from a variety of clinical information taken from four medical centers across the United States. The source data included medical as well as ample nursing terminology. The source records were coded in each scheme by an investigator and checked by the coding scheme owner. The codings were then scored by an independent panel of clinicians for acceptability. Codes were checked for definitions provided with the scheme. Codes for a random sample of source records were analyzed by an investigator for "parent" and "child" codes within the scheme. Parent and child pairs were scored by an independent panel of medical informatics specialists for clinical acceptability. Administrative and billing code mapping from the published scheme were reviewed for all coded records and analyzed by independent reviewers for accuracy. The investigator for each scheme exhaustively searched a sample of coded records for duplications. RESULTS: SNOMED was judged to be significantly more complete in coding the source material than the other schemes (SNOMED* 70%; READ 57%; UMLS 50%; *p < .00001). SNOMED also had a richer clinical taxonomy judged by the number of acceptable first-degree relatives per coded concept (SNOMED* 4.56, UMLS 3.17; READ 2.14, *p < .005). Only the UMLS provided any definitions; these were found for 49% of records which had a coding assignment. READ and UMLS had better administrative mappings (composite score: READ* 40.6%; UMLS* 36.1%; SNOMED 20.7%, *p < .00001), and SNOMED had substantially more duplications of coding assignments (duplication rate: READ 0%; UMLS 4.2%; SNOMED* 13.9%, *p < .004) associated with a loss of clarity. CONCLUSION: No major terminology source can lay claim to being the ideal resource for a computer-based patient record. However, based upon this analysis of releases for April 1995, SNOMED International is considerably more complete, has a compositional nature and a richer taxonomy. Is suffers from less clarity, resulting from a lack of syntax and evolutionary changes in its coding scheme. READ has greater clarity and better mapping to administrative schemes (ICD-10 and OPCS-4), is rapidly changing and is less complete. UMLS is a rich lexical resource, with mappings to many source vocabularies. It provides definitions for many of its terms. However, due to the varying granularities and purposes of its source schemes, it has limitations for representation of clinical concepts within a computer-based patient record.

Abstracting and Indexing↗

Who should code orthopaedic inpatients? A comparison of junior hospital doctors and coding clerks.

Our principal aim was to determine whether coding for billing purposes is adequately completed by hospital doctors. We also wanted to determine whether events during the inpatient stay prompted coding. We investigated the completeness and accuracy of ICD9 and OPCS4 coding at two departments of orthopaedics. Coding was for billing purposes only; retrieval of clinical data was limited to individual cases. Junior Hospital Doctors (JHDs) undertook coding at one department, coding clerks at the other. At each side 100 sets of notes concerning inpatient admissions were reviewed. Coding clerks returned coding data of higher completeness and quality (completeness x accuracy) than JHDs, but of lower accuracy. Completeness of data from JHDs reflected motivation to code and this was influenced by events during the course of admission. JHDs coded best for patients undergoing elective surgery, and worst for patients managed non-operatively. Coding clerks coded for all groups equally well. In the current study coding data returned by JHDs was of lower completeness and accuracy than has been described for other coding systems. We attribute the lower completeness to the low motivation of JHDs when coding for billing purposes and the lower accuracy to difficulty in using the system. Motivation could be increased by incorporating coding into departmental audit, the generation of discharge summaries and record collection for personal logbooks.

Abstracting and Indexing↗

Experiments in coding clinical information: an analysis of clinicians using a computerized coding tool.

We present data from a controlled experiment with computerized browsing and encoding tool. Eighteen practicing clinicians were asked to extract medical concepts from narrative exercise cases using two approaches--traditional and computer-assisted use of ICD-9. Our results indicate that completeness of coding can be improved by up to 55% using a computerized coding tool; enforcing mandatory as opposed to optional modifier codes results in lower rates of incomplete coding (0 vs 55%), higher rates of correct coding (41 to 92%), and no change in the number of incorrect codings; and manual coding takes 100% longer than coding with the help of the computerized coding tool. Furthermore, clinicians need 59% more time for processing the whole set of codes than is suggested by the sum of individual codes. We conclude that use of a computerized coding tool can save time and result in higher quality coding However, de facto time spent on coding may be underestimated when looking at individual coding times instead of looking at the whole task of processing a clinical scenario.

Computers↗

The performance of three visual coding procedures and three computer programs in classification of electrocardiograms according to the Minnesota Code.

A test library composed of the ECG's of 228 patients with clinically proven myocardial infarction and 294 subjects without clinical evidence of infarction was used to assess the performance of three visual coding procedures and three computer programs designed to classify ECGs according to the Minnesota Code. The results showed that visual coding performed by one experienced senior coder tended to be more consistent than visual coding relying on two less experienced coders and arbitration of disagreements by a supervisor. There was no significant difference in coding results when only one preprocessed complex was coded in comparison with the more elaborate coding of the whole source ECG using majority rule. The coding performance of the three computer programs was similar to that of the visual coding procedures. It is concluded that computer coding of ECGs according to the Minnesota Code is feasible. Combined optimal use of automated coding and visual verification of selected items may still further improve coding precision. However, when judged against an ECG independent standard, the accuracy of all coding procedures in discriminating infarcts from non-infarcts according to the Minnesota code criteria is rather limited. 'Soft' criteria give a reasonable sensitivity with low specificity whereas the use of 'hard' criteria with adequate specificity results in a substantial drop in sensitivity.

Computers↗

Coding clinical information: analysis of clinicians using computerized coding.

Data are presented of a controlled experiment with a computerized browsing and encoding tool. Eighteen practicing clinicians extracted medical concepts from two narrative exercise cases using two approaches, traditional and computer-assisted use of ICD-9. Our results indicate that by using a computerized coding tool the completeness of coding can be improved by up to 55%, that by enforcing mandatory as opposed to optional modifier codes results in lower rates of incomplete coding (0 and 55%, respectively), higher rates of correct coding (41 to 92%) and no change in incorrect code, and that manual coding takes twice as long than coding with the help of the computerized coding tool. Clinicians need 59% more time for processing the whole set of codes than is suggested by the sum of individual codes. We conclude that the use of a computerized coding tool can save time and result in higher quality codes. However, the real time spent on coding may be underestimated when looking at individual coding times, instead of the whole task of processing a clinical scenario.

Disease↗

Agreement and coding reliability of the Minnesota and Mayo electrocardiographic coding systems.

PROBLEM: To determine whether diagnoses of myocardial infarction assigned by a system that uses Marquette 12SL electrocardiographic (ECG) codes with manual over-reading agree with diagnoses assigned by Minnesota ECG codes. STUDIES UNDERTAKEN: Agreement and recode reliability of Minnesota and Mayo coding systems based on 768 ECGs plus chest pain history and serum enzyme values were analyzed for a stratified random sample of 141 patients with an event in 1990 or 1991 coded as HICDA 410.x, 411, 413 or 796.9. The population was reconstructed from the stratified random sample so that population-based inferences could be made from the analysis. RESULTS: For the stratified random sample, exact agreement on 4 categories (evolving diagnostic, diagnostic, equivocal, or other ECG) between Mayo and Minnesota ECG coding was 53.9% (kappa = 0.37 +/- 0.05). Code-recode agreement was higher for Minnesota coding (83.0%; kappa = 0.74 +/- 0.05) compared with Mayo coding (73.8%; kappa = 0.64 +/- 0.05). The same pattern was present for the reconstructed population. For coding myocardial infarction based on the ECG, serum enzyme levels, and the presence or absence of ischemic chest pain, agreement between Mayo and Minnesota coding was 84.4% (kappa = 0.72 +/- 0.05) based on the stratified random sample and 81.7% (kappa = 0.67 +/- 0.06) based on the reconstructed population. For the stratified random sample, reliability of diagnosis of myocardial infarction was 93.6% (kappa = 0.88 +/- 0.04) for the Minnesota system and 94.3% (kappa = 0.90 +/- 0.03) for the Mayo system. CONCLUSION: ECG interpretation by the Mayo and Minnesota coding systems differs significantly, and Mayo ECG coding is less reliable than Minnesota ECG coding. Coding of myocardial infarction on the basis of ECGs, serum enzymes, and ischemic chest pain, however, is equally reliable for both systems.

Chest Pain↗

On the use of ZIP codes and ZIP code tabulation areas (ZCTAs) for the spatial analysis of epidemiological data.

BACKGROUND: While the use of spatially referenced data for the analysis of epidemiological data is growing, issues associated with selecting the appropriate geographic unit of analysis are also emerging. A particularly problematic unit is the ZIP code. Lacking standardization and highly dynamic in structure, the use of ZIP codes and ZIP code tabulation areas (ZCTA) for the spatial analysis of disease present a unique challenge to researchers. Problems associated with these units for detecting spatial patterns of disease are explored. RESULTS: A brief review of ZIP codes and their spatial representation is conducted. Though frequently represented as polygons to facilitate analysis, ZIP codes are actually defined at a narrower spatial resolution reflecting the street addresses they serve. This research shows that their generalization as continuous regions is an imposed structure that can have serious implications in the interpretation of research results. ZIP codes areas and Census defined ZCTAs, two commonly used polygonal representations of ZIP code address ranges, are examined in an effort to identify the spatial statistical sensitivities that emerge given differences in how these representations are defined. Here, comparative analysis focuses on the detection of patterns of prostate cancer in New York State. Of particular interest for studies utilizing local, spatial statistical tests, is that differences in the topological structures of ZIP code areas and ZCTAs give rise to different spatial patterns of disease. These differences are related to the different methodologies used in the generalization of ZIP code information. Given the difficulty associated with generating ZIP code boundaries, both ZIP code areas and ZCTAs contain numerous representational errors which can have a significant impact on spatial analysis. While the use of ZIP code polygons for spatial analysis is relatively straightforward, ZCTA representations contain additional topological features (e.g. lakes and rivers) and contain fragmented polygons that can hinder spatial analysis. CONCLUSION: Caution must be exercised when using spatially referenced data, particularly that which is attributed to ZIP codes and ZCTAs, for epidemiological analysis. Researchers should be cognizant of representational errors associated with both geographies and their resulting spatial mismatch, especially when comparing the results obtained using different topological representations. While ZCTAs can be problematic, topological corrections are easily implemented in a geographic information system to remedy erroneous aggregation effects.

Bias↗

Improving the efficiency of the genetic code by varying the codon length--the perfect genetic code.

The function of DNA is to specify protein sequences. The four-base "alphabet" used in nucleic acids is translated to the 20 base alphabet of proteins (plus a stop signal) via the genetic code. The code is neither overlapping nor punctuated, but has mRNA sequences read in successive triplet codons until reaching a stop codon. The true genetic code uses three bases for every amino acid. The efficiency of the genetic code can be significantly increased if the requirement for a fixed codon length is dropped so that the more common amino acids have shorter codon lengths and rare amino acids have longer codon lengths. More efficient codes can be derived using the Shannon-Fano and Huffman coding algorithms. The compression achieved using a Huffman code cannot be improved upon. I have used these algorithms to derive efficient codes for representing protein sequences using both two and four bases. The length of DNA required to specify the complete set of protein sequences could be significantly shorter if transcription used a variable codon length. The restriction to a fixed codon length of three bases means that it takes 42% more DNA than the minimum necessary, and the genetic code is 70% efficient. One can think of many reasons why this maximally efficient code has not evolved: there is very little redundancy so almost any mutation causes an amino acid change. Many mutations will be potentially lethal frame-shift mutations, if the mutation leads to a change in codon length. It would be more difficult for the machinery of transcription to cope with a variable codon length. Nevertheless, in the strict and narrow sense of coding for protein sequences using the minimum length of DNA possible, the Huffman code derived here is perfect.

Algorithms↗

An extended RNA code and its relationship to the standard genetic code: an algebraic and geometrical approach.

An algebraic and geometrical approach is used to describe the primaeval RNA code and a proposed Extended RNA code. The former consists of all codons of the type RNY, where R means purines, Y pyrimidines, and N any of them. The latter comprises the 16 codons of the type RNY plus codons obtained by considering the RNA code but in the second (NYR type), and the third, (YRN type) reading frames. In each of these reading frames, there are 16 triplets that altogether complete a set of 48 triplets, which specify 17 out of the 20 amino acids, including AUG, the start codon, and the three known stop codons. The other 16 codons, do not pertain to the Extended RNA code and, constitute the union of the triplets YYY and RRR that we define as the RNA-less code. The codons in each of the three subsets of the Extended RNA code are represented by a four-dimensional hypercube and the set of codons of the RNA-less code is portrayed as a four-dimensional hyperprism. Remarkably, the union of these four symmetrical pairwise disjoint sets comprises precisely the already known six-dimensional hypercube of the Standard Genetic Code (SGC) of 64 triplets. These results suggest a plausible evolutionary path from which the primaeval RNA code could have originated the SGC, via the Extended RNA code plus the RNA-less code. We argue that the life forms that probably obeyed the Extended RNA code were intermediate between the ribo-organisms of the RNA World and the last common ancestor (LCA) of the Prokaryotes, Archaea, and Eucarya, that is, the cenancestor. A general encoding function, E, which maps each codon to its corresponding amino acid or the stop signal is also derived. In 45 out of the 64 cases, this function takes the form of a linear transformation F, which projects the whole six-dimensional hypercube onto a four-dimensional hyperface conformed by all triplets that end in cytosine. In the remaining 19 cases the function E adopts the form of an affine transformation, i.e., the composition of F with a particular translation. Graphical representations of the four local encoding functions and E, are illustrated and discussed. For every amino acid and for the stop signal, a single triplet, among those that specify it, is selected as a canonical representative. From this mapping a graphical representation of the 20 amino acids and the stop signal is also derived. We conclude that the general encoding function E represents the SGC itself.

Amino Acids↗

Randomised crossover trial comparing the performance of Clinical Terms Version 3 and Read Codes 5 byte set coding schemes in general practice.

OBJECTIVE: To determine whether Clinical Terms Version 3 provides greater accuracy and consistency in coding electronic patient records than the Read Codes 5 byte set. DESIGN: Randomised crossover trial. Clinicians coded patient records using both schemes after being randomised in pairs to use one scheme before the other. SETTING: 10 general practices in urban, suburban, and rural environments in Norfolk. PARTICIPANTS: 10 general practitioners. SOURCE OF DATA: Concepts were collected from records of 100 patient encounters. MAIN OUTCOME MEASURES: Percentage of coded choices ranked as being exact representations of the original terms; percentage of cases where coding choice of paired general practitioners was identical; length of time taken to find a code. RESULTS: A total of 995 unique concepts were collected. Exact matches were more common with Clinical Terms (70% (95% confidence interval 67% to 73%)) than with Read Codes (50% (47% to 53%)) (P < 0.001), and this difference was significant for each of the 10 participants individually. The pooled proportion with exact and identical matches by paired participants was greater for Clinical Terms (0.58 (0.55 to 0.61)) than Read Codes (0.36 (0.33 to 0.39)) (P < 0.001). The time taken to code with Clinical Terms (30 seconds per term) was not significantly longer than that for Read Codes. CONCLUSIONS: Clinical Terms Version 3 performed significantly better than Read Codes 5 byte set in capturing the meaning of concepts. These findings suggest that improved coding accuracy in primary care electronic patient records can be achieved with the use of such a clinical terminology.

Adult↗

The genetic code: what is it good for? An analysis of the effects of selection pressures on genetic codes.

How did the "universal" genetic code arise? Several hypotheses have been put forward, and the code has been analyzed extensively by authors looking for clues to selection pressures that might have acted during its evolution. But this approach has been ineffective. Although an impressive number of properties has been attributed to the universal code, it has been impossible to determine whether selection on any of these properties was important in the code's evolution or whether the observed properties arose as a consequence of selection on some other characteristic. Therefore we turned the question around and asked, what would a genetic code look like if it had evolved in response to various different selection pressures? To address this question, we constructed a genetic algorithm. We found first that selecting on a particular measure yields codes that are similar to each other. Second, we found that the universal code is far from minimized with respect to the effects of mutations (or translation errors) on the amino acid compositions of proteins. Finally, we found that the codes that most closely resembled real codes were those generated by selecting on aspects of the code's structure, not those generated by selecting to minimize the effects of amino acid substitutions on proteins. This suggests that the universal genetic code has been selected for a particular structure-a structure that confers an important flexibility on the evolution of genes and proteins-and that the particular assignments of amino acids to codons are secondary.

Algorithms↗