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Fundamental differences between the methods of maximum likelihood and maximum posterior probability in phylogenetics.

Using a four-taxon example under a simple model of evolution, we show that the methods of maximum likelihood and maximum posterior probability (which is a Bayesian method of inference) may not arrive at the same optimal tree topology. Some patterns that are separately uninformative under the maximum likelihood method are separately informative under the Bayesian method. We also show that this difference has impact on the bootstrap frequencies and the posterior probabilities of topologies, which therefore are not necessarily approximately equal. Efron et al. (Proc. Natl. Acad. Sci. USA 93:13429-13434, 1996) stated that bootstrap frequencies can, under certain circumstances, be interpreted as posterior probabilities. This is true only if one includes a non-informative prior distribution of the possible data patterns, and most often the prior distributions are instead specified in terms of topology and branch lengths. [Bayesian inference; maximum likelihood method; Phylogeny; support.].

Bayes Theorem↗

Non-linear tests for identifying differentially expressed genes or genetic networks.

MOTIVATION: One of the recently developed statistics for identifying differentially expressed genetic networks is Hotelling T2 statistic, which is a quadratic form of difference in linear functions of means of gene expressions between two types of tissue samples, and so their power is limited. RESULTS: To improve the power of test statistics, a general statistical framework for construction of non-linear tests is presented, and two specific non-linear test statistics that use non-linear transformations of means are developed. Asymptotical distributions of the non-linear test statistics under the null and alternative hypothesis are derived. It has been proved that under some conditions the power of the non-linear test statistics is higher than that of the T2 statistic. Besides theory, to evaluate in practice the performance of the non-linear test statistics, they are applied to two real datasets. The preliminary results demonstrate that the P-values of the non-linear statistics for testing differential expressions of the genetic networks are much smaller than those of the T2 statistic. And furthermore simulations show the Type I errors of the non-linear statistics agree with the threshold used and the statistics fit the chi2 distribution. SUPPLEMENTARY INFORMATION: Supplementary data are available on Bioinformatics online.

Algorithms↗

Can public campaigns effectively change psychological determinants of safer sex? An evaluation of three Dutch campaigns.

This study evaluated the 1994, 1995 and 1996 Dutch safer sex campaigns as to their effectiveness in terms of improved attitudes, perceived social norms, self-efficacy and intentions regarding safer sex. The hypotheses were tested that variables become more positive when campaigns are conducted and less positive when campaigns are discontinued. A comprehensive design, including a baseline-post-test/post-test-only group design and a longitudinal or multiple assessment group design, was employed to exclude testing effects, history effects, cultural changes and sample differences as alternative explanations. The results show that despite high baseline levels, the campaigns positively affected all variables. Importantly, levels of all variables decreased when no campaign was conducted. It is concluded that campaigns are needed to maintain high levels of determinants of safer sex and that future campaign goals should be formulated in terms of stabilization instead of growth.

Adult↗

Selecting diagnostic tests for ruling out or ruling in disease: the use of the Kullback-Leibler distance.

BACKGROUND: To select a proper diagnostic test, it is recommended that the most specific test be used to confirm (rule in) a diagnosis, and the most sensitive test be used to establish that a disease is unlikely (rule out). These rule-in and rule-out concepts can also be characterized by the likelihood ratio (LR). However, previous papers discussed only the case of binary tests and assumed test results already known. METHODS: The author proposes using the 'Kullback-Leibler distance' as a new measure of rule-in/out potential. The Kullback-Leibler distance is an abstract concept arising from statistics and information theory. The author shows that it integrates in a proper way two sources of information--the distribution of test outcomes and the LR function. The index predicts the fate of an average subject before testing. RESULTS: Analysis of real and hypothetical data demonstrates its applications beyond binary tests. It works even when the conventional methods of dichotomization and ROC curve analysis fail. CONCLUSIONS: The Kullback-Leibler distance nicely characterizes the before-test rule-in/out potentials. It offers a new perspective from which to evaluate a diagnostic test.

Diagnostic Techniques and Procedures↗

High human immunodeficiency virus type 1 seroprevalence in men who have sex with men in Buenos Aires, Argentina: risk factors for infection.

OBJECTIVE: To determine human immunodeficiency virus (HIV) seroprevalence in a sample of men who have sex with men (MSM) in Buenos Aires City and to identify risk factors associated with HIV type 1 infection. METHODS: Participants were invited to receive HIV counselling and testing at "NEXO" (a gay non-governmental organization) by means of informative leaflets distributed in gay nightclubs, porno cinemas, gymnasiums, and in the streets. During the encounter, the study was explained by a trained social worker and individuals were invited to volunteer for the study. Diagnosis of HIV was performed using two screening tests and Western Blot assay was used as confirmatory. RESULTS: Human immunodeficiency virus was detected in 96 (13.8%; 95% CI: 11.4-16.7) of 694 MSM. Fourteen (14.6%) of the 96 HIV-positive MSM were already aware of their HIV serostatus. In univariate analysis, HIV-1 infection (odds ratio [OR] >1.5) was found to be associated with older age (30-39 years), being unemployed, a previous sexually transmitted disease (STD) history, and having an HIV-positive partner. Cocaine consumption and irregular use of condoms with occasional partners were also found to be risk factors. In multivariate logistic regression analysis, being unemployed (OR = 3.42; 95% CI: 1.17-9.99) and having an HIV-positive partner (OR = 2.67; 95% CI: 1.09-6.52) remained significant risk factors. DISCUSSION: The high HIV-1 prevalence observed suggests an urgent need for implementation of effective prevention campaigns. This represents the first cross-sectional epidemiological study of HIV among the high-risk group of MSM in Argentina.

Adult↗

Insertion events of CR1 retrotransposable elements elucidate the phylogenetic branching order in galliform birds.

Using standard phylogenetic methods, it can be hard to resolve the order in which speciation events took place when new lineages evolved in the distant past and within a short time frame. As an example, phylogenies of galliform birds (including well-known species such as chicken, turkey, and quail) usually show low bootstrap support values at short internal branches, reflecting the rapid diversification of these birds in the Eocene. However, given the key role of chicken and related poultry species in agricultural, evolutionary, general biological and disease studies, it is important to know their internal relationships. Recently, insertion patterns of transposable elements such as long and short interspersed nuclear element markers have proved powerful in revealing branching orders of difficult phylogenies. Here we decipher the order of speciation events in a group of 27 galliform species based on insertion events of chicken repeat 1 (CR1) transposable elements. Forty-four CR1 marker loci were identified from the draft sequence of the chicken genome, and from turkey BAC clone sequence, and the presence or absence of markers across species was investigated via electrophoretic size separation of amplification products and subsequent confirmation by DNA sequencing. Thirty markers proved possible to type with electrophoresis of which 20 were phylogenetically informative. The distribution of these repeat elements supported a single homoplasy-free cladogram, which confirmed that megapodes, cracids, New World quail, and guinea fowl form outgroups to Phasianidae and that quails, pheasants, and partridges are each polyphyletic groups. Importantly, we show that chicken is an outgroup to turkey and quail, an observation which does not have significant support from previous DNA sequence- and DNA-DNA hybridization-based trees and has important implications for evolutionary studies based on sequence or karyotype data from galliforms. We discuss the potential and limitations of using a genome-based retrotransposon approach in resolving problematic phylogenies among birds.

Animals↗

GIF-DB, a WWW database on gene interactions involved in Drosophila melanogaster development.

GIF-DB (Gene Interactions in the Fly Database) is a new WWW database (http://www-biol.univ-mrs.fr/ approximately lgpd/GIFTS_home_page. html ) describing gene molecular interactions involved in the process of embryonic pattern formation in the flyDrosophila melanogaster. The detailed information is distributed in specific lines arranged into an EMBL- (or SWISS-PROT-) like format. GIF-DB achieves a high level of integration with other databases such as FlyBase, EMBL and SWISS-PROT through numerous hyperlinks. The original concept of interaction databases examplified by GIF-DB could be extended to other biological subjects and organisms so as to study gene regulatory networks in an evolutionary perspective.

Animals↗

IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences.

IMGT/LIGM-DB is the IMGT comprehensive database of immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and other vertebrate species. It was created in 1989 by LIGM, Montpellier, France and is the oldest and the largest database of IMGT. IMGT/LIGM-DB includes all germline (non-rearranged) and rearranged IG and TR genomic DNA (gDNA) and complementary DNA (cDNA) sequences published in generalist databases. IMGT/LIGM-DB allows searches from the Web interface according to biological and immunogenetic criteria through five distinct modules depending on the user interest. For a given entry, nine types of display are available including the IMGT flat file, the translation of the coding regions and the analysis by the IMGT/V-QUEST tool. IMGT/LIGM-DB distributes expertly annotated sequences. The annotations hugely enhance the quality and the accuracy of the distributed detailed information. They include the sequence identification, the gene and allele classification, the constitutive and specific motif description, the codon and amino acid numbering, and the sequence obtaining information, according to the main concepts of IMGT-ONTOLOGY. They represent the main source of IG and TR gene and allele knowledge stored in IMGT/GENE-DB and in the IMGT reference directory. IMGT/LIGM-DB is freely available at http://imgt.cines.fr.

Animals↗

Unlocking hidden genomic sequence.

Despite the success of conventional Sanger sequencing, significant regions of many genomes still present major obstacles to sequencing. Here we propose a novel approach with the potential to alleviate a wide range of sequencing difficulties. The technique involves extracting target DNA sequence from variants generated by introduction of random mutations. The introduction of mutations does not destroy original sequence information, but distributes it amongst multiple variants. Some of these variants lack problematic features of the target and are more amenable to conventional sequencing. The technique has been successfully demonstrated with mutation levels up to an average 18% base substitution and has been used to read previously intractable poly(A), AT-rich and GC-rich motifs.

AT Rich Sequence↗

Survey of the Italian Registry of Renal Biopsies. Frequency of the renal diseases for 7 consecutive years. The Italian Group of Renal Immunopathology.

PURPOSE: This report describes data collected by the Italian Registry of Renal Biopsies (IRRB) (E mail http://www.teseo.it/nephrology/irrb), which includes 15461 renal biopsies (RB) performed over a period of 7 years (1987-1993). METHODS: From 1987 to 1988, the Registry recorded only the histological diagnosis of 3686 RB, whereas beginning in 1989, additional records (sex, age, clinical symptoms and renal function) were obtained from 11,775 patients undergoing RB. This is the first report on such a large number of RB containing data from 96% of Italian renal units which routinely perform RB. RESULTS: In 13,835 RB performed in native kidneys, two groups of renal diseases, primary (59.9%) and secondary (25.4%) glomerulonephritis (gn), were more frequent than others. Among primary gn, the frequency of cases of IgAN, membranous gn, and focal and segmental glomerulosclerosis were 36.9, 21.7 and 10.4% respectively. Renal disease due to immune-mediated causes (51%) and dysgammaglobulinaemia (26.9%) were the most frequent among secondary gn. In the former group, the frequency of cases with lupus nephritis and vasculitis were 51.6 and 25.9% respectively. Renal amyloidosis (39.3%), essential mixed cryoglobulinaemia (30.9%), and multiple myeloma were the most frequent forms in the latter group. In 1993 the incidence of the following groups of renal disease was: primary gn (22.7 p.m.p.), secondary gn (11.1 p.m.p.) of which immune-mediated gn (5.8 p.m.p.), dysgammaglobulinaemias associated with nephritis (2.4 p.m.p.). IgAN and membranous gn, as primary gn, had an incidence of 8.4 and 4.9 p.m.p, respectively, while lupus nephritis (2.6 p.m.p.) and renal vasculitis (1.6 p.m.p.) were the most frequent forms of secondary gn. Clinical data regarding 10357 RB collected during 5 years (1989-1993), showed that the most common indications to perform RB were urinary abnormalities (30.8%) and nephrotic syndrome (27.1%), followed by recurrent episodes of macrohaematuria (8.7%) and nephritic syndrome (5.4%). Acute renal failure was present in 9.2% of patients and chronic renal insufficiency in 18.8% of cases. Membranous gn (32.9%), focal and segmental glomerulosclerosis (12.3%), and minimal-change disease (12.0%) were the most frequent diagnoses in patients with nephrotic syndrome, while post-streptococcal gn (16.1%) and IgAN (14.0%) were frequent in the nephritic syndrome. IgAN was frequently found in patients with urinary abnormalities (29.8%) and recurrent episodes of macrohematuria (71.4%). Twenty per cent of the acute renal insufficiency cases were secondary to necrotizing vasculitis, while chronic renal failure was present in 16.6% of the IgAN patients. FUTURE TRENDS: The IRRB is considering to extend its programme to include (i) paediatric section regarding RB from patients aged less than 18 years; (ii) annual review of clinical data concerning the kidney function of selected groups of patients recorded in IRRB, and (iii) the listing of IRRB records on the INTERNET, to facilitate the distribution of information throughout the scientific community.

Adult↗

Modulation of mitochondrial respiration by nitric oxide: investigation by single cell fluorescence microscopy.

With the electro-driven import of rhodamine 123, we used single cell fluorescence microscopy to single out the contribution of nitric oxide (NO) in controlling mitochondrial membrane potential expressed by (stationary growing) rhabdomyosarcoma and neuroblastoma cells in culture. The experimental design and the computer-aided image analysis detected and quantitated variations of fluorescence signals specific to mitochondria. We observed that 1) the two cell lines display changes of fluorescence dependent on mitochondrial energization states; 2) mitochondrial fluorescence decreases after exposure of the cells to a NO releaser; 4) the different fluorescence intensity measured under stationary growing conditions, or after activation and inhibition of constitutive NO synthase, is consistent with a steady-state production of NO. Direct comparison of single cell fluorescence with bulk cytofluorimetry proved that the results obtained by the latter method may be misleading because of the intrinsic-to-measure lack of information about distribution of fluorescence within different cell compartments. The kinetic parameters describing the reactions between cytochrome oxidase, NO, and O2 may account for the puzzling (20-fold) increase of the KM for O2 reported for cells and tissues as compared to purified cytochrome c oxidase, allowing an estimate of in vivo NO flux.

Fluorescence↗

Health fairs: An avenue for colon health promotion in the community.

Colon cancer is the number two cause of cancer deaths in both men and women in the United States. Colon cancer is 90% treatable if diagnosed early, yet only 41% of Americans over age 50 who should be screened have been. Two of the reasons why so many people are not screened include the lack of public awareness about colorectal cancer and the need for regular screening, and the lack of social support for discussion of the "disease down there." GI nurses can use hospital, community, and university health fairs as an opportunity to educate their communities on the prevention of and screening for colon cancer. Suggestions are given on how to: be included in a health fair, set up the booth, obtain information to distribute, develop a display of educational materials, "hook" the audience, and educate attendees on a cancer prevention diet and exercise program. The American Cancer Society Screening Guidelines and factors that increase colon cancer risk are listed. A colon cancer screening questionnaire is included for attendees to take home, complete, and discuss with their private physicians. A health fair is presented as a fun way to promote the prevention of and screening for colon cancer.

Colonic Neoplasms↗

Local lung ventilation in critically ill patients using nonradioactive xenon-enhanced transmission computed tomography.

Nonradioactive xenon is sufficiently radiodense to increase the density of gas-containing lung as seen in a computed tomography (CT) scan. Subtraction of a baseline CT scan from the xenon-enhanced CT scan can accentuate gas space differences by subtracting fixed tissue densities. The baseline scan and the scan obtained during wash-in of xenon (before equilibration) allow circulation of local ventilation. The xenon CT scan, thus, provides more precise information about distribution of ventilation than planar radiogas techniques. The technical aspects of application to a critically ill patient and the mathematical basis of the technique are presented.

Humans↗

Innovative solutions: pharmacy and nursing collaboration on a high-risk medication project.

Banner Good Samaritan Medical Center is a 650-bed tertiary care facility in the Southwestern United States. The pharmacy and nursing departments collaborated on a multifocal project to address the educational and operational needs of the facility regarding the new JCAHO Medication Management Review Standards for high-risk and high-alert medications. The project encompassed policy creation, nursing education, identification and evaluation of HRHA medications, and facility-wide distribution of information related to high-risk and high-alert medications.

Cooperative Behavior↗

Development of a method to estimate thyroid dose from fallout radioiodine in a cohort study.

A cohort of 4831 persons aged 11-18 y in 1965 was identified among students in the schools of Washington County, UT; Lincoln County, NV; and Graham County, AZ. These children who had potentially been exposed to radioiodine from atomic weapons test fallout from the Nevada Test Site during 1951-1962 were selected for participation in a study of thyroid disease. The entire cohort was first examined during 1965-1968 for thyroid abnormalities. A total of 3,085 of these people were again reexamined during 1985-1986 to determine any subsequent occurrence of thyroid disease. In order to determine the relationship of the radiation dose to the thyroid with incidence of thyroid disease, we have developed a suite of models to calculate estimates of the internal dose received by the thyroid from fallout radioiodines. For completeness, the exposure to the thyroid from external radiation is also estimated. Dose estimates are made specific to each individual in the study using individual residential histories, the locality-specific exposure rate and radionuclide deposition, descriptions of dairy management for identified milk producers, and the subjects' sources of foods and intake rates of milk and leafy vegetables determined by interview. Other data such as the relationship of radioiodine deposition to measured exposure rate, environmental transfer parameters, and age-dependent factors for the conversion of radioiodine intake to thyroid dose were taken from work of other investigators. Dairy management information, milk distribution practices, the milk source for each study subject, as well as age-specific intake rates of milk and leafy vegetables, were determined by interview.

Adolescent↗

The gas fireplace: a new burn hazard in the home.

Gas fireplaces have become popular in recent years. This article presents the first reported case of a burn injury from contact with the glass front of a gas fireplace. An investigation of the surface temperature of the glass fronts of gas fireplaces was undertaken to clarify the risks posed by these units. Surface temperature measurements of the glass fronts of 3 common gas fireplace models were obtained using a thermocouple probe. Glass temperatures reached 200 degrees C within 6.5 minutes of ignition, climbing to 245 degrees C at 14 minutes after ignition. Glass temperature continued to rise beyond this point, but it could not be monitored because the adhesives securing the thermocouple probe melted. Glass temperatures of 50 degrees C were recorded at 30 minutes after the unit was shut off. The temperatures of the glass fronts of glass fireplaces are sufficient to cause cutaneous burns within seconds of contact both while the fireplace is in use and up to one half hour after it has been turned off. Current industry safety standards are not directed at the prevention of contact burns. We recommend that (1) mechanical guards be installed to create a barrier in front of the glass; (2) strict warning labels be applied to the units and ignition switches; and (3) burn prevention information be distributed with the owner's manual for these products.

Accidents, Home↗