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Multiple sclerosis sibling pairs: clustered onset and familial predisposition.

We evaluated 48 relapsing-remitting multiple sclerosis (R/R MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS. Age- and sex-matched R/R MS clinic patients provided a statistical comparison group. The age of onset tended to cluster within multiplex families. The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls. A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls. In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members. Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds.

Adult↗

Coulomb explosion of K-shell ionized krypton clusters studied by multiple-ion coincidence momentum imaging.

The Coulomb explosion of K-shell ionized krypton clusters with an average size N of 160 has been studied by electron-multiple-ion-coincidence measurements in which the time-of-flight (TOF) of ions was measured by using a position sensitive detector. The authors have sorted the TOF spectra by the number of coincidence ion signals, Ncoin, and found that singly charged fragment ions such as Kr+, Kr2+, and Kr3+ are dominant for Ncoin>or=2, and that multiply charged ions are detected mainly for Ncoin=1. The Ncoin dependence of the peak widths in the TOF spectra reveals that the average momentum of the Kr+ ions increases with Ncoin, while those of Kr2+ and Kr3+ decrease. These results have been more directly confirmed by the momentum imaging measurements. The authors propose that the heavier ions are produced in the central part of clusters where the Coulomb interactions from the surrounding ions are more effectively canceled out due to the higher symmetry.

Journal Article↗

Assessing the effect of a single dose florfenicol treatment in feedlot cattle on the antimicrobial resistance patterns in faecal Escherichia coli.

The objective of this clinical trial was to examine the effect of a single dose of florfenicol on antimicrobial resistance patterns in faecal E. coli of feedlot steers. Steers (n = 370), were purchased from two sources and housed in outdoor concrete floored pens. Two cattle from each pen (n = 42 pens, 84 cattle) were randomly selected for faecal sampling at study day 1, 14, 28, and 42. One sampled animal from each of 21 pens was randomly selected to receive a single 39.6 mg/kg dose of florfenicol subcutaneously at study day 11. Ten lactose positive colonies were isolated from faecal swabs and tested for antimicrobial resistance to 11 antimicrobials using the disk diffusion method. Zones of inhibition were grouped using cluster analysis and clusters were ordered by increasing multiple resistance. A cumulative logistic regression model using generalized estimating equations was used to assess factors associated with increasing levels of multiple resistance. Immediately post-treatment, all isolates obtained from treated cattle belonged to multiple resistant clusters containing chloramphenicol resistance. Though less pronounced in later sampling, resistance to chloramphenicol and other antimicrobials persisted. Antimicrobial treatment, sampling time and animal source, as well as interactions between these variables, were important predictors of the odds of E. coli belonging to a more resistant cluster. A very clear but transitory shift to increasingly multiple resistant faecal E. coli in response to florfenicol treatment was observed. There was no indication of horizontal transfer of resistant E. coli between steers. Level of resistance was influenced by complex interaction of animal source and previous management.

Animals↗

Medical record linkage in health information systems by approximate string matching and clustering.

BACKGROUND: Multiplication of data sources within heterogeneous healthcare information systems always results in redundant information, split among multiple databases. Our objective is to detect exact and approximate duplicates within identity records, in order to attain a better quality of information and to permit cross-linkage among stand-alone and clustered databases. Furthermore, we need to assist human decision making, by computing a value reflecting identity proximity. METHODS: The proposed method is in three steps. The first step is to standardise and to index elementary identity fields, using blocking variables, in order to speed up information analysis. The second is to match similar pair records, relying on a global similarity value taken from the Porter-Jaro-Winkler algorithm. And the third is to create clusters of coherent related records, using graph drawing, agglomerative clustering methods and partitioning methods. RESULTS: The batch analysis of 300,000 "supposedly" distinct identities isolates 240,000 true unique records, 24,000 duplicates (clusters composed of 2 records) and 3,000 clusters whose size is greater than or equal to 3 records. CONCLUSION: Duplicate-free databases, used in conjunction with relevant indexes and similarity values, allow immediate (i.e. real-time) proximity detection when inserting a new identity.

Algorithms↗

Clustering and group selection of multiple criteria alternatives with application to space-based networks.

In many real-world problems, the range of consequences of different alternatives are considerably different. In addition, sometimes, selection of a group of alternatives (instead of only one best alternative) is necessary. Traditional decision making approaches treat the set of alternatives with the same method of analysis and selection. In this paper, we propose clustering alternatives into different groups so that different methods of analysis, selection, and implementation for each group can be applied. As an example, consider the selection of a group of functions (or tasks) to be processed by a group of processors. The set of tasks can be grouped according to their similar criteria, and hence, each cluster of tasks to be processed by a processor. The selection of the best alternative for each clustered group can be performed using existing methods; however, the process of selecting groups is different than the process of selecting alternatives within a group. We develop theories and procedures for clustering discrete multiple criteria alternatives. We also demonstrate how the set of alternatives is clustered into mutually exclusive groups based on 1) similar features among alternatives; 2) ideal (or most representative) alternatives given by the decision maker; and 3) other preferential information of the decision maker. The clustering of multiple criteria alternatives also has the following advantages. 1) It decreases the set of alternatives to be considered by the decision maker (for example, different decision makers are assigned to different groups of alternatives). 2) It decreases the number of criteria. 3) It may provide a different approach for analyzing multiple decision makers problems. Each decision maker may cluster alternatives differently, and hence, clustering of alternatives may provide a basis for negotiation. The developed approach is applicable for solving a class of telecommunication networks problems where a set of objects (such as routers, processors, or intelligent autonomous vehicles) are to be clustered into similar groups. Objects are clustered based on several criteria and the decision maker's preferences.

Journal Article↗

Clusters of diverse genes existing as multiple, sequence-variable mosaics in a phytoplasma genome.

Phytoplasmas are cell wall-less prokaryotes living as obligate parasites and pathogens of plants and insects, making them attractive subjects for studies to gain a greater understanding of transkingdom parasitism and pathogenicity. During a study of two phytoplasma genomes, we obtained evidence for previously unreported clustering of genes, pseudogenes, mobile genetic elements, intergenic repeat units, and repetitive extragenic palindromes that occur in multiple, homologous clusters in some phytoplasma genomes. The clusters represent previously unrecognized mosaics, possibly assembled through multiple events of targeted mobile element attack, duplication, recombination, and rearrangement. Multiple clusters could conceivably afford potential for genome reduction through homologous recombination. Differences in the sizes and multiplicity of such clusters possibly account for some of the previously reported but unexplained variations in genome size among closely related phytoplasma strains.

Base Sequence↗

Multiple alignment and hierarchical clustering of conserved amino acid sequences in the replication-associated proteins of plant RNA viruses.

We have used multiple alignment computer programs to align and hierarchically cluster the conserved amino acid "signature" sequences found in the replication-associated proteins of all plant RNA viruses sequenced so far. These regions, called "polymerase", "nucleotide-binding" and "N-terminal" are well conserved even between viruses which are only distantly related, and are thus very well suited for this type of analysis. Our results show that the clusterings obtained using these very short amino acid sequences are very robust to computing parameters and are surprisingly well matched with the taxonomic grouping of RNA plant viruses. The possibility of using this system as a new taxonomic criterion is discussed.

Amino Acid Sequence↗

Multiple sequence alignment with hierarchical clustering.

An algorithm is presented for the multiple alignment of sequences, either proteins or nucleic acids, that is both accurate and easy to use on microcomputers. The approach is based on the conventional dynamic-programming method of pairwise alignment. Initially, a hierarchical clustering of the sequences is performed using the matrix of the pairwise alignment scores. The closest sequences are aligned creating groups of aligned sequences. Then close groups are aligned until all sequences are aligned in one group. The pairwise alignments included in the multiple alignment form a new matrix that is used to produce a hierarchical clustering. If it is different from the first one, iteration of the process can be performed. The method is illustrated by an example: a global alignment of 39 sequences of cytochrome c.

Algorithms↗

Fine-scale mapping of disease genes with multiple mutations via spatial clustering techniques.

We present a method to perform fine mapping by placing haplotypes into clusters on the basis of risk. Each cluster has a haplotype "center." Cluster allocation is defined according to haplotype centers, with each haplotype assigned to the cluster with the "closest" center. The closeness of two haplotypes is determined by a similarity metric that measures the length of the shared segment around the location of a putative functional mutation for the particular cluster. Our method allows for missing marker information but still estimates the risks of complete haplotypes without resorting to a one-marker-at-a-time analysis. The dimensionality issues that can occur in haplotype analyses are removed by sampling over the haplotype space, allowing for estimation of haplotype risks without explicitly assigning a parameter to each haplotype to be estimated. In this way, we are able to handle haplotypes of arbitrary size. Furthermore, our clustering approach has the potential to allow us to detect the presence of multiple functional mutations.

Algorithms↗

Use of multiple correspondence analysis and cluster analysis to study dietary behaviour: food consumption questionnaire in the SU.VI.MAX. cohort.

Although the effects of individual foods or nutrients on the development of diseases and their risk factors have been investigated in many studies, little attention has been given to the effect of overall dietary patterns. The main objectives of this study were to identify dietary patterns and groups of subjects with similar food consumption habits, i.e. 'dietary profiles', using multiple correspondence analysis and cluster analysis. A food frequency questionnaire was sent to a large population-based sample (2923 women and 2,180 men), recruited among the 'SUpplementation en VItamines et Minéraux AntioXydants' (SU.VI.MAX.) cohort participants in France. The food items were dichotomised in order to focus the study on the highest levels of consumption. Multiple correspondence analysis allows the construction of principal components, which optimally summarise the data, and enables the construction of graphical displays. An interesting property of these graphical displays is that associations between food items can be observed on various projection planes, each category of each food item being located at the centre of gravity of the subjects corresponding to this category. An ascending hierarchical classification was unsuccessfully tried in order to determine clusters from these principal components. Therefore, a 'dissection' of the cloud of points was performed according to the orientation of the axes, providing a readily interpretable eight-dietary profiles typology for each sex. This statistical approach allows identification of particular dietary patterns and dietary profiles, which might be more appropriate in studies of diet-disease associations than the single food or nutrient approach that has dominated past epidemiological research.

Adult↗

Multiple false reactions in viral antibody screening assays after influenza vaccination.

In December 1991, US blood centers reported an unusual increase in donations that tested falsely reactive for antibodies to two or more (multiple false positive) of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type I (HTLV-I), and hepatitis C virus. Many of these donations were from people who had recently received the 1991-1992 influenza vaccine, raising the possibility that this vaccine had somehow specifically caused the problem of multiple false reactivity. A case-control study of 101 affected donors and 191 matched controls found that recent receipt of any brand of influenza vaccine was significantly associated with testing multiple false positive (p < 0.05), as was a history of recent acute illness (p < 0.05) and of allergies (p < 0.05). Surveillance for monthly rates of multiple reactive donations from May 1990 through December 1992 linked the seasonal cluster of multiple false-positive donations to the use of viral screening test kits thought to react nonspecifically to donor immunoglobulin M. There was no similar increase in multiple false-positive donations during the 1992-1993 influenza vaccination season after the HIV-1 and hepatitis C virus tests were replaced; however, the number of donations that were falsely reactive for only HTLV-I almost doubled, indicating that false reactivity was not specifically associated with the 1991-1992 influenza vaccine. Retesting of affected donors found that the duration of HTLV-I and hepatitis C virus false reactivity was 3-6 months. The cluster of multiple false-positive donations in 1991 was most likely caused by the test kits used, rather than by the influenza vaccine.

Adolescent↗

Evidence for multiple lateral transfers of the circadian clock cluster in filamentous heterocystic cyanobacteria Nostocaceae.

Cyanobacteria are the first prokaryotes reported to show circadian rhythmicity, which is regulated by a cluster of three genes: kaiA, kaiB, and kaiC. Phylogenetic analysis of the kaiBC cluster in filamentous cyanobacteria of the family Nostocaceae including Nodularia spumigena and Nostoc linckia from Arubotaim Cave, Mt. Sedom, Israel, indicated that this cluster has experienced multiple lateral transfers. The transfers have occurred in different periods of the species' evolution. The data obtained suggest that lateral transfers of the circadian clock cluster in filamentous cyanobacteria have been common and might have adaptive significance.

Amino Acid Sequence↗

Molecular epidemiology of human calicivirus gastroenteritis outbreaks in Hungary, 1998 to 2000.

Between November 1998 and November 2000, 196 stool specimens from 21 outbreaks of acute nonbacterial gastroenteritis occurring in 11 of the 19 counties of Hungary were collected and tested for human caliciviruses. Human caliciviruses were detected and characterized by a type-common enzyme-linked immunosorbent assay (EIA) and reverse transcription-polymerase chain reaction (RT-PCR) followed by cloning and sequencing. Twenty (95%) and 14 (67%) outbreaks were positive by EIA and RT-PCR, respectively, and 12 RT-PCR-positive outbreaks were also confirmed by sequencing. Comparative sequence analysis revealed 13 Norwalk-like virus sequences in the 12 outbreaks, including 11 Norwalk-like virus genogroup II (seven in Hawaii-like, two Lordsdale-like, one Melksham-like, and one Hillingdon-like) and two Norwalk-like virus genogroup I (related to Southampton-like and Desert Shield-like clusters) viruses. Multiple Norwalk-like virus clusters, with a predominance of Hawaii-like viruses, played an important role in nonbacterial gastroenteritis outbreaks during the study period. This is the first country-wide molecular epidemiological investigation of human calicivirus-associated, gastroenteritis outbreaks in Hungary and Central-Eastern Europe.

Adolescent↗

Multiple outputation: inference for complex clustered data by averaging analyses from independent data.

This article applies a simple method for settings where one has clustered data, but statistical methods are only available for independent data. We assume the statistical method provides us with a normally distributed estimate, theta, and an estimate of its variance sigma. We randomly select a data point from each cluster and apply our statistical method to this independent data. We repeat this multiple times, and use the average of the associated theta's as our estimate. An estimate of the variance is given by the average of the sigma2's minus the sample variance of the theta's. We call this procedure multiple outputation, as all "excess" data within each cluster is thrown out multiple times. Hoffman, Sen, and Weinberg (2001, Biometrika 88, 1121-1134) introduced this approach for generalized linear models when the cluster size is related to outcome. In this article, we demonstrate the broad applicability of the approach. Applications to angular data, p-values, vector parameters, Bayesian inference, genetics data, and random cluster sizes are discussed. In addition, asymptotic normality of estimates based on all possible outputations, as well as a finite number of outputations, is proven given weak conditions. Multiple outputation provides a simple and broadly applicable method for analyzing clustered data. It is especially suited to settings where methods for clustered data are impractical, but can also be applied generally as a quick and simple tool.

Acute Disease↗

Association of charge clusters with functional domains of cellular transcription factors.

Using rigorous statistical methods, we have identified and evaluated unusual properties of the distribution of charged residues within the sequences of eukaryotic cellular transcription factors. Virtually all transcription factors, including GAL4, c-Jun, C/EBP, CREB, Oct-1, Oct-2, Sp1, Egr-1, CTF-1, steroid and thyroid hormone receptors, and others, carry one or more highly significant charge clusters. For the most part these clusters (conserved within families of homologous proteins) are of positive net charge but contain also substantial numbers of acidic residues. Predominantly basic charge clusters are often, but not exclusively, associated with DNA-binding domains, and vice versa. Negative charge clusters of note occur only in the yeast protein PHO4 and in the proteins encoded at the Drosophila loci zeste (zeta) and knrl. This dearth of statistically significant negative charge clusters raises questions with respect to the generality of acidic activation domains. A number of sequences (Oct-1, Oct-2, zeste, Dhr23, E75, and knrl) contain multiple charge clusters together with one or more significantly long uncharged regions. The occurrence of multiple charge clusters is a rare phenomenon (found in less than 3% of all proteins, mainly in Drosophila developmental control proteins and in transactivators of eukaryotic DNA viruses). Most of the proteins with zinc-binding "fingers" carry a mixed charge cluster centered at the zinc-finger motif preceded by a long uncharged stretch, suggestive of a modular structure for these proteins.

Animals↗

HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside.

A spontaneous semidominant mutation (Ironside, Irn) was isolated in mice, leading to severe hindlimb paralysis following multiple deletions in cis at the HoxD locus. To understand its cellular and molecular etiology, we embarked on a comparative analysis using systematic HoxD cluster deletions, produced via targeted meiotic recombination (TAMERE). Different lines of mice were classified according to the severity of their paralyses, and subsequent analyses revealed that multiple causative factors were involved, alone or in combination, in the occurrence of this pathology. Among them are the loss of Hoxd10 function, the sum of remaining Hoxd gene activity, and the ectopic gain of function of the neighboring gene Evx2, all contributing to the mispositioning, the absence, or misidentification of specific lumbo-sacral pools of motoneurons, nerve root homeosis, and hindlimb innervation defects. These results highlight the importance of a systematic approach when studying such clustered gene families, and give insights into the function and regulation of Hox and Evx2 genes during early spinal cord development.

Abnormalities, Multiple↗

Improved temporal clustering analysis method for detecting multiple response peaks in fMRI.

PURPOSE: To develop an improved temporal clustering analysis (TCA) method for detecting multiple active peaks by running the method once. MATERIALS AND METHODS: Two cases of simulation data and a set of actual fMRI data from nine subjects were used to compare the traditional TCA method with the new method, termed extremum TCA (ETCA). The first case of simulation data simulated event-related activation and block activation in one cerebral area, and the second case simulated event-related activation and block activation in two cerebral areas. An in vivo visual stimulating experiment was performed on a 1.5T MR scanner. All imaging data were processed using both traditional TCA and the new method. RESULTS: The results of both the simulated and actual fMRI data show that the new method is more sensitive and exact than traditional TCA in detecting multiple response peaks. CONCLUSION: The new method is effective in detecting multiple activations even when the timing and location of the brain activation are completely unknown.

Brain Mapping↗

Cluster headache variant. Spectrum of a new headache syndrome.

The syndrome of cluster headache variant is characterized by the occurrence of three combined symptoms: atypical cluster headaches, multiple jabs, and background vascular headaches. Atypical cluster headaches are localized headaches that occur several times daily, usually without any headache-free periods. They differ from the typical chronic cluster headache in their location, duration, frequent shifting, and frequency. Multiple jabs are short-lasting, sharp pains of variable severity and location. Background vascular headache is a chronic, continuous often unilateral headache of variable severity that throbs at rest or begins to throb during exertion. We have studied 54 patients between the ages of 14 and 78 years (average age, 40.5 years). Forty-five (83%) patients responded to indomethacin. Complete control was achieved in 50% of the patients. The nine patients who did not respond to indomethacin were depressed. These nine patients responded well to tricyclic antidepressants.

Adult↗