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Recursive partitioning identifies patients at high and low risk for ipsilateral tumor recurrence after breast-conserving surgery and radiation.

PURPOSE: Recursive partitioning analysis (RPA), a method of building decision trees of significant prognostic factors for outcome, was used to determine subgroups at significantly different risk for ipsilateral breast tumor recurrence (IBTR) in early-stage breast cancer. PATIENTS AND METHODS: Nine hundred twelve women underwent breast-conserving surgery, axillary dissection, and radiation. Systemic therapy was chemotherapy with or without tamoxifen in 32%, tamoxifen in 27%, or none in 41%. RPA was used to create a decision tree according to predictive variables that classify patients by IBTR risk, and the Kaplan-Meier method was used to calculate 10-year risks. Median follow-up was 5.9 years. RESULTS: Age was the first split in the partition tree. Patients more than 55 years old had a 4% 10-year IBTR, the only further division being use of tamoxifen or not (2% v 5%, P =.03). For patients </= 55 years old, extensive intraductal component (EIC) was the next significant split. For EIC-negative tumors, age </= 35 years and negative margins were associated with a 10-year IBTR of 3%; with close (</= 2 mm) or positive margins, 34%. Patients 36 to 55 years old with estrogen receptor-positive tumors receiving tamoxifen had a risk of IBTR of 5%, but had a 20% risk without tamoxifen. CONCLUSION: This RPA showed that age </= 55 versus more than 55 years was the most significant factor for IBTR. Patients </= 35 years old had a low risk of IBTR when tumors were EIC-negative with negative margins. EIC was an independent factor for IBTR for ages </= 55 years. Use of tamoxifen was the most significant factor for patients older than 55 years, but it resulted in a greater absolute decrease in risk of IBTR for patients 36 to 55 years old.

Actuarial Analysis↗

Geometrical assessment of ocular exposure to environmental UV radiation--implications for ophthalmic epidemiology.

Epidemiological studies of the influence of environmental ultraviolet radiation (UVR) in the development of cataract, pterygium, droplet keratopathies and age-related macular degeneration have produced inconsistent findings. The lack of consistent results may be due largely to either incomplete or erroneous estimates of outdoor UV exposure dose. Geometrical factors dominate the determination of UVR exposure of the eye. The degree of lid opening limits ocular exposure to only those rays entering at angles near the horizon. Clouds redistribute overhead UVR to the horizon sky. Mountains, trees and building shield the eye from direct sky exposure. Most ground surfaces reflect little UVR. The result is that the highest UVR exposure occurs during light overcast where the horizon is visible and ground surface reflection is high. By contrast, exposure in a high mountain valley with green foliage results in a much lower ocular dose. Other findings of these studies show that retinal exposure to light and UVR in daylight occurs largely in the superior retina.

Animals↗

Genetic and transmission analysis of Helicobacter pylori strains within a family.

To look for evidence of intrafamilial infection, we isolated 107 Helicobacter pylori clones from biopsied specimens taken from both parents and four children. We compared the sequences of two housekeeping genes (hspA and glmM) from these clones with those of 131 unrelated strains from patients living in different geographic regions. Strain relationships within the family were determined by analyzing allelic variation at both loci and building phylogenetic trees and by using multilocus sequence typing. Both hspA- and glmM-based phylogenetic trees showed East Asian and African branches. All samples from family members showed natural mixed infection. Identical alleles found in some strains isolated from the children and parents, but not in the strains isolated from unrelated patients, demonstrated that strains have circulated within the family. Several mechanisms, such as point mutations, intragenic recombination, and introduction of foreign (African) alleles, were shown to enhance strain diversity within the family.

Adolescent↗

Shifting constraints on tRNA genes during mitochondrial DNA evolution in animals.

During the evolution of echinoderm mitochondrial (mt) DNA, a transfer RNA gene lost its tRNA function and became part of a protein-coding gene. To examine the evolutionary consequences of this event, we sequenced 961 bp of mtDNA in five sea urchin species. This enabled us to build a tree relating the mtDNAs and use it for analyzing the pattern and process of evolutionary substitutions in the former leucine tRNA gene, which now is a 5' extension of the gene for NADH dehydrogenase subunit 5 (ND5). This 5' extension is now evolving at the same rate and under the same protein-coding constraints as the rest of ND5. The adjacent (upstream) serine tRNA gene, however, has been evolving at a reduced rate, consistent with the possibility that it has assumed a punctuation role in processing of the primary transcript that was once fulfilled by the former leucine tRNA gene.

Animals↗

Risk factors in mass screening for breast cancer, multivariate analysis of data from the Cuban diagnosis pilot study.

The evolution of mammography has provided possibilities for mass screening programs. Early diagnosis is considered the most important factor in reducing the breast cancer mortality but the mass screening is very expensive if we include all female population. In this paper we show the results of an early diagnosis pilot study with a multivariate data analysis. Data concerning risk factors (age, age at menarche, menopause, parity, age at first childbirth, lactation, abortions and previous benign breast disease) were recorded in 438 patients with breast carcinoma and 1750 patients with benign breast diseases diagnosed in the Early Diagnosis Pilot Program at the National Institute of Oncology and Radiobiology in Cuba. A group of 449 healthy women living in Havana City was also studied. Age and age at first childbirth were the major factor considered. Multivariate data analysis allowed to build stratification trees identifying subgroups with different breast cancer incidence. The usefulness of these stratifications for screening with optimal coverage, sufficiency and efficacy, is discussed.

Adult↗

Evaluation of benefits from amenity and wildlife conservation.

Vague statement concerning the desirability of conserving trees, old buildings, wildlife, or other assets, which contribute to public welfare without increasing the Gross National Produce, are commonplace; but they are not, in themselves, precise enough to facilitate decision-taking in particular instances or in the general allocation of funds or resources in the economy. There is, therefore, a need for the adoption of valuation procedures, similar to those outlined, together with a more sensible approach towards the discounting of future values, and a closer consideration of the sort of environment and life-style towards which we are striving.

Conservation of Natural Resources↗

ROSE: decision trees, automatic learning and their applications in cardiac medicine.

Computerized information systems, especially decision support systems, have acquired an increasingly important role in medical applications, particularly in those where important decisions must be made effectively and reliably. But the possibility of using computers in medical decision making is limited by many difficulties, including the complexity of conventional computer languages, methodologies, and tools. Thus a conceptual simple decision making model with the possibility of automating learning should be used. In this paper, we introduce a cardiological knowledge-based system based on the decision tree approach supporting the mitral valve prolapse determination. Prolapse is defined as the displacement of a bodily part from its normal position. The term mitral valve prolapse (PMV), therefore, implies that the mitral leaflets are displaced relative to some structure, generally taken to be the mitral annulus. The implications of the PMV are: disturbed normal laminar blood flow, turbulence of the blood flow, injury of the chordae tendinae, the possibility of thrombus's composition, bacterial endocarditis, and, finally, hemodynamic changes defined as mitral insufficiency and mitral regurgitation. Uncertainty persists about how it should be diagnosed and about its clinical importance. It is our deep belief that the echocardiography enables properly trained expert armed with proper criteria to evaluate PMV almost 100%. But, unfortunately, there are some problems concerned with the use of echocardiography. With this in mind, we have decided to start a research project aimed at finding new criteria and enabling the general practitioner to evaluate the PMV using conventional methods and to select potential patients from the general population. To empower doctors to perform needed activities, we have developed a computer tool called ROSE (computeRized prOlaps Syndrome dEtermination) based on algorithms of automatic learning. This tool supports the definition of new criteria and the selection of potential PMV-patients. The ROSE is based on concepts of decision trees and automatic learning. The decisions and learning process can be presented with an easily visualized two dimensional model; thus decision trees are straightforward to build and interpret. Decision trees use different object attributes to classify different subsets of objects. (Their great advantage is that they don't use a fixed number of predetermined attributes.) In the decision tree approach, the members of a set of objects are classified as either positive or negative instances (in our case patients with PMV Syndrome or without it). Candidate attributes that may possibly describe the concept are then outlined. A decision tree construction tool uses outlined attributes to formulate the appropriate decision tree that identifies all positive instances of the underlying concept according to objects with known classification. (In our case the classification is done with the echo examination). The first set of objects used for the tree generation is usually called the training set. This decision tree characterization next becomes a basis: 1) forecasting whether an object previously unseen is a positive or negative instance of the concept being modeled, and 2) the hierarchical representation of the most important attributes of the concept being investigated. Our main interest and idea is to discover symptoms, syndromes, and illnesses related to PMV that can be distinguished by general practitioners in their everyday job and which should help them to identify possible PMV candidate patients. To this end, we constructed a computerized tool called ROSE. According to the principles presented above, we first taught ROSE using the sample of 400 examined volunteers. ROSE, considering that the clinical PMV diagnosis is practically not researched, is relatively successful. (abstract truncated)

Algorithms↗

Bacterial molecular phylogeny using supertree approach.

It has been claimed that complete genome sequences would clarify phylogenetic relationships between organisms but, up to now, no satisfying approach has been proposed to use efficiently these data. For instance, if the coding of presence or absence of genes in complete genomes gives interesting results, it does not take into account the phylogenetic information contained in sequences and ignores hidden paralogy by using a similarity-based definition of orthology. Also, concatenation of sequences of different genes takes hardly in consideration the specific evolutionary rate of each gene. At last, building a consensus tree is strongly limited by the low number of genes shared among all organisms. Here, we use a new method based on supertree construction, which permits to cumulate in one supertree the information and statistical support of hundreds of trees from orthologous gene families and to build the phylogeny of 33 prokaryotes and four eukaryotes with completely sequenced genomes. This approach gives a robust supertree, which demonstrates that a phylogeny of prokaryotic species is conceivable and challenges the hypothesis of a thermophilic origin of bacteria and present-day life. The results are compatible with the hypothesis of a core of genes for which lateral transfers are rare but they raise doubts on the widely admitted "complexity hypothesis" which predicts that this core is mainly implicated in informational processes.

Bacteria↗

[The application of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in diagnosing dysplasia and chronic atrophic gastric-carditis in population with high risk of gastric-cardia adenocarcinoma].

OBJECTIVES: To evaluate the serum biomarkers for diagnosis of gastric cardia dysplasia (DYS) and chronic atrophic gastric-carditis (CAG) and to provide a novel screening method for high risk population of gastric-cardia adenocarcinoma (GCA). METHODS: Proteomic spectra were generated by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS) and weak cation exchange protein chip system. A set of spectra derived from analysis of serum from 143 symptom-free subjects at high-risk area for GCA, including 63 cases with histologically normal gastric cardia epithelia, 57 of CAG and 23 of DYS, were analyzed by bioinformatics like decision tree classification algorithm. The sensitivity and the specificity for test group were performed by using 10-fold cross validation classification with the decision tree classification model. RESULTS: One protein spot with a ratio of mass to charge (M/Z) of M3894. 0 was selected to build a decision tree classification model to identify the case with DYS or normal. With this classification model, the sensitive rate for DYS identification was 87% (20/23). Two proteins with M/Z of M2942. 15 and M33316. 6 were used to build a decision tree classification model. With this model, the sensitivity for discriminating CAG from normal was 93% (53/57) and the specificity was 92 (58/63). CONCLUSIONS: The gastric cardia lesions of DYS and CAG could be identified by SELDI-TOF-MS technique specifically in symptom-free subjects at high incidence area for GCA. The present findings provide a new screening way for high-risk subjects with CGA.

Adult↗

A phylogenomic approach to bacterial phylogeny: evidence of a core of genes sharing a common history.

It has been claimed that complete genome sequences would clarify phylogenetic relationships between organisms, but up to now, no satisfying approach has been proposed to use efficiently these data. For instance, if the coding of presence or absence of genes in complete genomes gives interesting results, it does not take into account the phylogenetic information contained in sequences and ignores hidden paralogies by using a BLAST reciprocal best hit definition of orthology. In addition, concatenation of sequences of different genes as well as building of consensus trees only consider the few genes that are shared among all organisms. Here we present an attempt to use a supertree method to build the phylogenetic tree of 45 organisms, with special focus on bacterial phylogeny. This led us to perform a phylogenetic study of congruence of tree topologies, which allows the identification of a core of genes supporting similar species phylogeny. We then used this core of genes to infer a tree. This phylogeny presents several differences with the rRNA phylogeny, notably for the position of hyperthermophilic bacteria.

Computational Biology↗

[Program-target method in hospital management].

The experience gained in developing the system of targets for a number of urban multi-profile hospitals suggests an opportunity for using a programme-target method in the management of an inpatient facility. The Samashko All-Union Research Institute of Social Hygiene, Public Health Economics and Management has developed a system of programme-target management, consisting of relatively autonomous blocks: the identification of actually existing hospital problems; the elaboration of the conception of hospital development; the building of a tree of targets; the projecting of structures for hospital management; the elaboration and implementation of programmes. The identification of problems is based on the analysis of factographic tree of hospital targets. The analysis of the problem situation and possible ways of solving the problems allow to elaborate the conception of hospital development. In order to simplify the procedure for the building of a tree of targets the subdivision of targets into the targets-results, targets-processes and targets-objects is being introduced. On the basis of tree of targets the structure of management is being projected and programmes are being developed. The uniformity of methods used in this system makes it possible to presuppose the possibility of applying them at any institution and at any level of public health management.

Hospital Administration↗

Techniques for the verification of minimal phylogenetic trees illustrated with ten mammalian haemoglobin sequences.

We have recently reported a method to identify the shortest possible phylogenetic tree for a set of protein sequences [Foulds Hendy & Penny (1979) J. Mol. Evol. 13. 127--150; Foulds, Penny & Hendy (1979) J. Mol. Evol. 13, 151--166]. The present paper discusses issues that arise during the construction of minimal phylogenetic trees from protein-sequence data. The conversion of the data from amino acid sequences into nucleotide sequences is shown to be advantageous. A new variation of a method for constructing a minimal tree is presented. Our previous methods have involved first constructing a tree and then either proving that it is minimal or transforming it into a minimal tree. The approach presented in the present paper progressively builds up a tree, taxon by taxon. We illustrate this approach by using it to construct a minimal tree for ten mammalian haemoglobin alpha-chain sequences. Finally we define a measure of the complexity of the data and illustrate a method to derive a directed phylogenetic tree from the minimal tree.

Amino Acid Sequence↗

Multipolar consensus for phylogenetic trees.

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

Algorithms↗

SST: an algorithm for finding near-exact sequence matches in time proportional to the logarithm of the database size.

MOTIVATION: Searches for near exact sequence matches are performed frequently in large-scale sequencing projects and in comparative genomics. The time and cost of performing these large-scale sequence-similarity searches is prohibitive using even the fastest of the extant algorithms. Faster algorithms are desired. RESULTS: We have developed an algorithm, called SST (Sequence Search Tree), that searches a database of DNA sequences for near-exact matches, in time proportional to the logarithm of the database size n. In SST, we partition each sequence into fragments of fixed length called 'windows' using multiple offsets. Each window is mapped into a vector of dimension 4(k) which contains the frequency of occurrence of its component k-tuples, with k a parameter typically in the range 4-6. Then we create a tree-structured index of the windows in vector space, with tree-structured vector quantization (TSVQ). We identify the nearest neighbors of a query sequence by partitioning the query into windows and searching the tree-structured index for nearest-neighbor windows in the database. When the tree is balanced this yields an O(logn) complexity for the search. This complexity was observed in our computations. SST is most effective for applications in which the target sequences show a high degree of similarity to the query sequence, such as assembling shotgun sequences or matching ESTs to genomic sequence. The algorithm is also an effective filtration method. Specifically, it can be used as a preprocessing step for other search methods to reduce the complexity of searching one large database against another. For the problem of identifying overlapping fragments in the assembly of 120 000 fragments from a 1.5 megabase genomic sequence, SST is 15 times faster than BLAST when we consider both building and searching the tree. For searching alone (i.e. after building the tree index), SST 27 times faster than BLAST. AVAILABILITY: Request from the authors.

Algorithms↗

Building k edge-disjoint spanning trees of minimum total length for isometric data embedding.

Isometric data embedding requires construction of a neighborhood graph that spans all data points so that geodesic distance between any pair of data points could be estimated by distance along the shortest path between the pair on the graph. This paper presents an approach for constructing k-edge-connected neighborhood graphs. It works by finding k edge-disjoint spanning trees the sum of whose total lengths is a minimum. Experiments show that it outperforms the nearest neighbor approach for geodesic distance estimation.

Algorithms↗

The influence of urban design on outdoor thermal comfort in the hot, humid city of Colombo, Sri Lanka.

The outdoor environment is deteriorating in many tropical cities due to rapid urbanization. This leads to a number of problems related to health and well-being of humans and also negatively affects social and commercial outdoor activities. The creation of thermally comfortable microclimates in urban environments is therefore very important. This paper discusses the influence of street-canyon geometry on outdoor thermal comfort in Colombo, Sri Lanka. Five sites with different urban geometry, ground cover, and distance from the sea were studied during the warmest season. The environmental parameters affecting thermal comfort, viz. air temperature, humidity, wind speed, and solar radiation, were measured, and the thermal comfort was estimated by calculating the physiologically equivalent temperature (PET). The thermal comfort is far above the assumed comfort zone due to the combination of intense solar radiation, high temperatures, and low wind speeds, especially on clear days. The worst conditions were found in wide streets with low-rise buildings and no shade trees. The most comfortable conditions were found in narrow streets with tall buildings, especially if shade trees were present, as well as in areas near the coast where the sea breeze had a positive effect. In order to improve the outdoor comfort in Colombo, it is suggested to allow a more compact urban form with deeper street canyons and to provide additional shade through the use of trees, covered walkways, pedestrian arcades, etc. The opening up of the city's coastal strip would allow the sea breeze to penetrate further into the city.

Cities↗

How much energy do barn owls (Tyto alba) save by roosting?

(1) The energy savings associated with the roosting behaviour of barn owls (Tyto alba) were determined with a biophysical model using measurements of microclimate from a roost and nest site in SW Scotland (55 degrees 10' N 3 degrees 12' W) from April 1991-March 1992. (2) The roost building provided complete shelter from wind and precipitation. Air temperature inside the roost building was 1.4 degrees C greater than ambient and matched the seasonal change in temperature. Air temperature inside the nest box was on average only 0.8 degrees C greater than ambient but was 2-3 degrees C warmer when adults and chicks were in the nest during the breeding season. (3) Estimated metabolic heat production was significantly different between locations and averaged 67.9, 68.1, 75.5 and 84.2Wm(-2) for a barn owl roosting in the building, nest box, spruce tree and in the open, respectively. At night metabolic heat production was greater by 4-12% compared with daytime, depending on location. (4) Heat loss was 30% greater in winter months than in the summer in all locations. By roosting in the building an owl would make savings of 21.6Wm(-2) in March but only 12.9Wm(-2) in August. In a tree roost a barn owl would save 11.8Wm(-2) in March and 5.8Wm(-2) in August. (5) Barn owls were estimated to reduce metabolic heat production by 19% by roosting in the building and by 10% by roosting in a tree. In the building and tree savings of 21 and 9% occurred during the day compared with 17 and 12% at night. (6) Metabolic savings were strongly dependent on weather conditions with average metabolic savings of 26% occurring in wet and windy conditions compared with only 12% on dry-calm days. Maximum savings of 29-36% occurred on wet days. (7) Barn owls appear to compensate for high metabolic demands for heat production by taking advantage of better thermal conditions within buildings, especially during the day when metabolic savings are greatest.

Journal Article↗

Fold recognition via a tree.

Recently, we developed a pairwise structural alignment algorithm using realistic structural and environmental information (SAUCE). In this paper, we at first present an automatic fold hierarchical classification based on SAUCE alignments. This classification enables us to build a fold tree containing different levels of multiple structural profiles. Then a tree-based fold search algorithm is described. We applied this method to a group of structures with sequence identity less than 35% and did a series of leave one out tests. These tests are approximately comparable to fold recognition tests on superfamily level. Results show that fold recognition via a fold tree can be faster and better at detecting distant homologues than classic fold recognition methods.

Algorithms↗