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Exploratory analysis and a stochastic model for humusdisintegration.

Ulrich (1981) supposes in the hypothesis of humusdisintegration that the balance between polymerisation and breakdown of organic material may be disturbed in chemically well buffered European forest soils. This new aspect of aluminium toxicity may cause nitrogen exceedance in forest ecosystems and subsequent seasonal nitrate output (Eichhorn and Hutterman, 1999). In a research program the substances in the seepage water are monitored in a small woodland in central Germany. We explore these multivariate data for examining possible influences on the process of humusdisintegration and its temporal evolution. As a result, a regression model for carbon is developed, which includes covariables, i.e., other substances, as well as spatial and temporal terms describing systematic variability. Especially iron and aluminium turn out to be very influential in the model. So far our work is a basic step for monitoring the seepage water data by means of stochastic modelling.

Aluminum↗

Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic survey of 100 cases.

OBJECTIVES: To assess the diagnostic usefulness of the systematic analysis of synovial vascular morphology in various inflammatory, early, and longstanding arthropathies, and to examine the validity of the vascular patterns in predicting the evolution of a group of patients with undifferentiated arthritis (UA). METHODS: One hundred patients who underwent rheumatologic arthroscopy of a symptomatic joint (85 knees, 11 wrists, 3 elbows, 1 metacarpophalangeal joint) were evaluated. The same observer, blinded to patient diagnosis, analyzed the video recordings of the arthroscopies. Vascular morphology was classified into 3 patterns: straight, tortuous, and mixed. RESULTS: Eighty-one patients had inflammatory arthritis: 35 rheumatoid arthritis (RA), 16 psoriatic arthritis (PsA), 13 spondyloarthropathies (SpA), and 17 UA. Forty-nine percent of patients with RA had a straight pattern, 28% a mixed, and 23% a tortuous one. The sensitivity rate of the straight pattern for RA was 77% and the specificity rate was 70%. Seventy-six percent of RA patients with a straight pattern were rheumatoid factor positive (RF+) against 25% of RA patients with a tortuous pattern. The odds ratio for RA associated to straight compared with tortuous pattern was 57.3 (95% confidence interval, 6.6 to 499.5; P <.001). Patients with PsA and SpA shared the same pattern and were analyzed as 1 group. Ninety-three percent of patients with PsA/SpA had a tortuous pattern, 4% a straight pattern, and 3% a mixed pattern. The sensitivity rate of the tortuous pattern for PsA/SpA was 61% and the specificity rate was 95%. During 2 years of follow-up, 6 of 17 patients with UA were definitely diagnosed: 4 RA (2 RF+ and straight pattern; 2 with a tortuous pattern, 1 with RF+ and HLA-B27+); 1 SpA and 1 PsA, both with a tortuous pattern. No differences in vascular patterns were observed according to disease duration. Our results indicate that vascular patterns are not modified by disease modifying antirheumatic drug (DMARD) treatment. The other 19 patients had osteoarthritis (n = 8) and calcium pyrophosphate dihydrate crystal deposition disease (n = 11) and their predominant vascular pattern was tortuous-like. CONCLUSIONS: Arthroscopic assessment of synovial vascular changes in chronic arthritis may be of diagnostic and pathogenetic interest, although differences between published studies suggest a need for consensus in evaluating vascular patterns. A straight pattern is strongly associated with RF + RA whereas a tortuous pattern is generally associated with PsA or SpA; these associations are independent of disease duration. The vascular pattern likely does not change qualitatively with DMARD therapy. The application of this technique to the diagnosis or prognosis of patients with UA may be a complementary tool for the treatment of these patients, but larger, prospective studies are necessary to confirm this hypothesis.

Adolescent↗

Acute pyelonephritis: analysis of 52 cases.

Acute pyelonephritis (APN) is a frequent disease, but diagnostic approach, evolution into abscesses, and indication to hospitalization are still open problems. We have made a retrospective analysis of APN cases observed in our hospital. We identified 58 patients (pt) and selected 52 of these who presented fever and loin pain at the onset (31 were hospitalized in Nephrology and 21 in other units). Urine culture was positive in 11/48 cases (22.9%), blood cultures in 3/26 cases (11.5%) (Escherichia coli). Renal sonography was normal in 20/48 cases (41.6%) and suggestive for APN in 23/48 cases (47.9%). CT with contrast medium was normal in 9/28 cases (32.1%) and positive in 19/28 cases (67.8%), with evidence of unique or multiple hypodense areas; abscesses were found in 8 patients (28.5%). No statistically significant differences were found between patients with positive or negative CT as regards fever, leukocytosis, ESR, CRP, CRP at 20 days, urinary leukocytes, urine culture, duration of symptoms before hospitalization. Moreover no differences were found between patients with and without abscesses. CT was performed more frequently among patients hospitalized in Nephrology than among patients hospitalized in other services (24/31-77.4%-vs. 4/21-19%-, p = 0.05). NMR was abnormal in 6/9 cases. A radiographic documentation of APN was obtained in 61.53% of patients with clinical diagnosis of APN. Of these, only 18.7% had positive urine culture. In conclusion, our data suggest that demonstration of urine infection is not necessary for APN diagnosis, when clinical and/or radiologic diagnosis of APN has been made. Evolution into abscesses is frequent and not easily susceptible on clinical ground; for this reason we think it is advisable to perform CT or NMR systematically. Differences in clinical behavior between different units suggest the need for diagnostic guidelines.

Acute Disease↗

Global protein function annotation through mining genome-scale data in yeast Saccharomyces cerevisiae.

As we are moving into the post genome-sequencing era, various high-throughput experimental techniques have been developed to characterize biological systems on the genomic scale. Discovering new biological knowledge from the high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed a Bayesian statistical method together with Boltzmann machine and simulated annealing for protein functional annotation in the yeast Saccharomyces cerevisiae through integrating various high-throughput biological data, including yeast two-hybrid data, protein complexes and microarray gene expression profiles. In our approach, we quantified the relationship between functional similarity and high-throughput data, and coded the relationship into 'functional linkage graph', where each node represents one protein and the weight of each edge is characterized by the Bayesian probability of function similarity between two proteins. We also integrated the evolution information and protein subcellular localization information into the prediction. Based on our method, 1802 out of 2280 unannotated proteins in yeast were assigned functions systematically.

Bayes Theorem↗

Protein design from in silico dynamic information: the emergence of the 'turn-dock-lock' motif.

A protein design methodology based on ab initio folding simulations is described and illustrated. First, the time evolution of the chain topology is generated to identify a collapse-triggering nucleus. Then, a minimal spliced sequence of nuclear residues is created and systematically mutated in silico until it can sustain a stable conformation retaining the original nucleus topology. The mutations introduce a structural compensation for the deletions and eventually lead to the recovery of the native fold motif beyond topological identity. For ubiquitin, the systematically modified sequence is predicted to be a resilient folder, since it is 92% homologous to the hyperthermophile variant of B1-domain in streptococcal protein G. The methodology enabling us to identify the nucleus is independently validated vis-á-vis site-directed mutagenesis experiments on chymotrypsin inhibitor (CI2).

Algorithms↗

Fossilized embryos are widespread but the record is temporally and taxonomically biased.

We report new discoveries of embryos and egg capsules from the Lower Cambrian of Siberia, Middle Cambrian of Australia and Lower Ordovician of North America. Together with existing records, embryos have now been recorded from four of the seven continents. However, the new discoveries highlight secular and systematic biases in the fossil record of embryonic stages. The temporal window within which the embryos and egg capsules are found is of relatively short duration; it ends in the Early Ordovician and is roughly coincident with that of typical "Orsten"-type faunas. The reduced occurrence of such fossils has been attributed to reducing levels of phosphate in marine waters during the early Paleozoic, but may also be owing to the increasing depth of sediment mixing by infaunal metazoans. Furthermore, most records younger than the earliest Cambrian are of a single kind-large eggs and embryos of the priapulid-like scalidophoran Markuelia. We explore alternative explanations for the low taxonomic diversity of embryos recovered thus far, including sampling, size, anatomy, ecology, and environment, concluding that the preponderance of Markuelia embryos is due to its precocious development of cuticle at an embryonic stage, predisposing it to preservation through action as a substrate on which microbially mediated precipitation of authigenic calcium phosphate may occur. The fossil record of embryos may be limited to a late Neoproterozoic to early Ordovician snapshot that is subject to dramatic systematic bias. Together, these biases must be considered seriously in attempts to use the fossil record to arbitrate between hypotheses of developmental and life history evolution implicated in the origin of metazoan clades.

Animals↗

The anatomy of clinical research.

Until recently clinical decision-making relied on intuition, unsystematic experiences and pathophysiological rationale. Developments in the understanding of the nature of clinical trials, systematic reviews and techniques to evaluate diagnostic technology over the past 30 years made the evidence-based clinical practice possible. During this period of evolution it became apparent that not all evidence is equal. Studies that use weak designs tend to estimate a greater treatment effect, whereas strong designs yield a more conservative treatment effect. A good number of orthodontic problems lend themselves to investigations of controlled clinical trials. Reports of early treatment effectiveness of malocclusions contained in this issue demonstrate the point.

Decision Making↗

Modeling the lag time of Listeria monocytogenes from viable count enumeration and optical density data.

The following two factors significantly influence estimates of the maximum specific growth rate ( micro (max)) and the lag-phase duration (lambda): (i) the technique used to monitor bacterial growth and (ii) the model fitted to estimate parameters. In this study, nine strains of Listeria monocytogenes were monitored simultaneously by optical density (OD) analysis and by viable count enumeration (VCE) analysis. Four usual growth models were fitted to our data, and estimates of growth parameters were compared from one model to another and from one monitoring technique to another. Our results show that growth parameter estimates depended on the model used to fit data, whereas there were no systematic variations in the estimates of micro (max) and lambda when the estimates were based on OD data instead of VCE data. By studying the evolution of OD and VCE simultaneously, we found that while log OD/VCE remained constant for some of our experiments, a visible linear increase occurred during the lag phase for other experiments. We developed a global model that fits both OD and VCE data. This model enabled us to detect for some of our strains an increase in OD during the lag phase. If not taken into account, this phenomenon may lead to an underestimate of lambda.

Colony Count, Microbial↗

Intraabdominal fetal echogenic masses: a practical guide to diagnosis and management.

Intraabdominal calcifications and other echogenic masses are relatively common findings during fetal sonography. Many are associated with no additional risk for the fetus or neonate. They may arise from the liver, gallbladder, spleen, kidneys, adrenal glands, gastrointestinal tract, or peritoneal cavity. Detection of such lesions should prompt a detailed survey for additional findings and a review of the maternal history. In some cases, fetal karyotyping may be indicated. In most cases, the diagnosis, management, and outcome are determined according to a combination of specific ultrasound appearances and at least one additional maternal or fetal factor. In utero diagnosis can often be achieved with careful evaluation of the lesion echotexture, associated calcifications, additional findings, and evolution over time. In most cases, expectant management is sufficient, but some patients require transfer to a facility where early postnatal intervention is available. A systematic approach to the findings aids in differential diagnosis and management.

Abdominal Cavity↗

Skin ultrastructure in senile lentigo.

Senile lentigo is a common component of photoaged skin. It is characterized by hyperpigmented macules which affect chronically irradiated skin mostly after the age of 50. This study was undertaken to assess the morphology of senile lentigo on the dorsum of the hands. A systematic comparison between lesional and perilesional skin using histology and transmission electron microscopy was done to determine whether melanocytes or keratinocytes are affected in the evolution of lesions and which tissue structure is modified. The histology study showed that lesional skin is characterized by a hyperpigmented basal layer and an elongation of the rete ridges, which seem to drive deeply into the dermis. The epidermis contained clusters of keratinocytes, which retained and accumulated the melanin pigment. Electron microscopy studies showed important modifications in the lesional skin ultrastructure in comparison with perilesional skin. In melanocytes from perilesional and lesional skin, we observed normal size melanosomes at all stages of maturation in the cytoplasm and in migration within dendrites. No pigment accumulation was observed. However, the morphology of melanocytes in lesional skin revealed an activated status with numerous mitochondria and a well-developed endoplasmic reticulum, which could reflect intense protein synthesis. In basal keratinocytes from lesional skin, we observed numerous melanosome complexes called polymelanosomes, which formed massive caps on the nuclei. Observations in colored semi-thin sections also revealed perturbed structures in the basal layer region, which could explain the skin perturbation. Indeed, we observed keratinocytes that presented important microinvaginations and pendulum melanocytes, which sank into the dermis, beneath the basal layer of keratinocytes. These cell modifications seemed to be due to a perturbation of the dermal-epidermal junction, which appeared disorganized and disrupted and could directly disturb the basal support of the cells.

Aged↗

[Rhinophyma--conservative or surgical treatment?].

On the basis of a case of their own, the authors report on the evolution of a rhinophyma. Therapeutic results obtained with conservative treatment were not satisfactory. In contrast, a combination of surgical removal of the skin changes and systematic treatment with isotretinoin was associated with good results. Contraindications and possible side effects must always be borne in mind.

Combined Modality Therapy↗

[Functional recovery test. Evaluation of sequelae after buccopharyngeal surgery].

Hitherto, there have been few means to assess the immediate and secondary sequellae following the anatomic upheaval of buccopharyngeal carcinological exeresis. The functional recovery test, the various criteria of which are analyzed, to which 420 patients were subjected, makes it possible to record, for the 123 complete files, the regular evolution of the progress of each patient over a period of 12 months and beyond, which is stimulating and leads us to propose a more systematic handling of such operated patients by the team of phoniatricians and speech therapists.

Humans↗

[Benign clear cell tumour of the lung (author's transl)].

The benign clear cell tumor of the lung is an uncommon neoplasm. It is often confused, before histological analysis, with metastases. The data of one personal observation are similar to those of 19 other cases of the literature. This tumor which occurs with an equal frequency in adults of the two sexes is often asymptomatic. It is discovered after a systematic x-ray control of the lungs. It is located in the peripheral parenchyma and looks like a round, homogeneous, well delimited opacity. Its evolution is always favourable after surgical excision. The benign clear cell tumour is never identified before pathological study. This neoplasm 1 to 6 cm in diameter consists of a uniform proliferation of clear cells filled up with free of intra-vesicular glycogen. Its cytological and structural features are not the same as those of the other primitive bronchopulmonary tumours having an important clear cell contingent. The histochemical and ultra-structural studies are at the origin of three hypotheses; is the benign clear cell tumor an apudoma, a smooth muscular neoplasm or an adenoma of the terminal bronchioles?

Adult↗

[Natural evolution of radiculopathies and myelopathies caused by cervical arthrosis].

AIMS: From the data available in the literature, to analyse the natural history of acute or chronic radiculopathies and myelopathies linked with degenerative disease of the cervical spine. DEVELOPMENT: By means of different electronic and manual search methods, we located original pieces of work dealing with recent objectives and reviews on the subject. We have attempted to take into account any data that might be relevant, regardless of the characteristics or quality of the work in which it was published. The high prevalence of degenerative changes in the cervical region in the general population, the fact that the development of the concept of cervical radiculopathies and myelopathies has gone parallel to the development of their surgical treatment, and that there are few series with a control group and independent evaluation and no trials with random assignation do not allow a systematic approach. The anatomical and radiological aspects of cervical arthrosis are well known, but there is little information available on the causal relation between both processes and their clinical translation or their natural evolution. CONCLUSIONS: In the present state of knowledge, it is not possible to establish unmistakable relations between cervical disc disease and the radiculopathies and myelopathies it is attributed with. The natural evolution of these neurological syndromes is not known and therefore neither is it known how this could be modified by conservative or surgical treatment. From critical points of view, there is a unanimous claim for clinical trials to be performed with random assignation, which would provide us with an understanding of the natural history of these entities and the role of the different surgical or conservative treatments available

Cervical Vertebrae↗

Phylogenetic incongruence among oncogenic genital alpha human papillomaviruses.

The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whole-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the LILD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncogenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incongruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophyletic across all genes.

DNA Viruses↗

Synteny conservation and chromosome rearrangements during mammalian evolution.

An important problem in comparative genome analysis has been defining reliable measures of synteny conservation. The published analytical measures of synteny conservation have limitations. Nonindependence of comparisons, conserved and disrupted syntenies that are as yet unidentified, and redundant rearrangements lead to systematic errors that tend to overestimate the degree of conservation. We recently derived methods to estimate the total number of conserved syntenies within the genome, counting both those that have already been described and those that remain to be discovered. With this method, we show that approximately 65% of the conserved syntenies have already been identified for humans and mice, that rates of synteny disruption vary approximately 25-fold among mammalian lineages, and that despite strong selection against reciprocal translocations, inter-chromosome rearrangements occurred approximately fourfold more often than inversions and other intra-chromosome rearrangements, at least for lineages leading to humans and mice.

Animals↗

Evolution of the Emergency Management of Severe Burns (EMSB) course in the UK.

The principle of the 'golden hour' is now well established and forms the basis of a growing number of instructional courses teaching a systematic approach to the management of major trauma. In April 1997, the EMSB course, developed by the Australian and New Zealand Burn Association, was adopted by the British Burn Association to meet the needs of health professionals dealing with major burn injuries in this country. The experience of the first 13 courses following the introduction of EMSB is discussed and the course is recommended as a requirement for the training of UK plastic surgeons and plastic surgery nurses.

Burns↗

Enhancement, relaxation, and reversal of the stereoselectivity for phosphotriesterase by rational evolution of active site residues.

The factors that govern the substrate reactivity and stereoselectivity of phosphotriesterase (PTE) toward organophosphotriesters containing various combinations of methyl, ethyl, isopropyl, and phenyl substituents at the phosphorus center were determined by systematic alterations in the dimensions of the active site. The wild type PTE prefers the S(P)-enantiomers over the corresponding R(P)-enantiomers by factors ranging from 10 to 90. Enlargement of the small subsite of PTE with the substitution of glycine and alanine residues for Ile-106, Phe-132, and/or Ser-308 resulted in significant improvements in k(cat)/K(a) for the R(P)-enantiomers of up to 2700-fold but had little effect on k(cat)/K(a) for the corresponding S(P)-enantiomers. The kinetic preferences for the S(P)-enantiomers were thus relaxed without sacrificing the inherent catalytic activity of the wild type enzyme. A reduction in the size of the large subsite with the mutant H257Y resulted in a reduction in k(cat)/K(a) for the S(P)-enantiomers, while the values of k(cat)/K(a) for the R(P)-enantiomers were essentially unchanged. The initial stereoselectivity observed with the wild type enzyme toward the chiral substrate library was significantly reduced with the H257Y mutant. Simultaneous alternations in the sizes of the large and small subsites resulted in the complete reversal of the chiral specificity. With this series of mutants, the R(P)-enantiomers were preferred as substrates over the corresponding S(P)-enantiomers by up to 500-fold. These results have demonstrated that the stereochemical determinants for substrate hydrolysis by PTE can be systematically altered through a rational reconstruction of the dimensions of the active site.

Amino Acid Substitution↗