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PubMed2006

Elevated microsatellite instability at selected tetranucleotide repeats does not correlate with clinicopathologic features of bladder cancer.

INTRODUCTION: The aim of the present study was to evaluate whether elevated microsatellite instability (MSI) at selected tetranucleotide repeats (EMAST) is associated with clinicopathologic and molecular parameters in urinary bladder cancer (BC). METHODS: A consecutive series of 117 nonselected urothelial BCs was studied. Microsatellite analysis and detection of loss of heterozygosity (LOH) was performed after microdissection by using 12 markers selected for sensitive detection of EMAST. Furthermore, five markers (BAT25, BAT26, D2S123, APC, and D17S250) of the Bethesda consensus panel for detection of colorectal cancer within the hereditary non-polyposis colon cancer syndrome (HNPCC) were analyzed. Expression of TP53 and mismatch repair (MMR) proteins hMSH2, hMLH1, and hMSH6 was investigated by immunohistochemistry. RESULTS: EMAST was detected in 10 of 117 patients (8.5%), whereas MSI in the HNPCC panel was found in one of 114 cases (0.9%). LOH in EMAST markers was seen in six of 114 (5.3%) cases. All tumours showed normal expression of hMSH2 and hMLH1. Overexpression of TP53 was observed in nine of 117 evaluated cases (7.7%). No association of EMAST and TP53 expression could be demonstrated. None of the clinicopathologic or molecular parameters were associated with EMAST. CONCLUSIONS: EMAST is another distinct form of MSI in urothelial BC. However, EMAST seems to be a rare event in non-selected urothelial BC and does not seem to be associated with commonly used clinicopathologic and clinical features in patients with BC.

Humans↗
PubMed2006

Role of colonoscopic biopsy in distinguishing between Crohn's disease and intestinal tuberculosis.

BACKGROUND: The histological differential diagnosis of Crohn's disease and intestinal tuberculosis can be very challenging, as both are chronic granulomatous disorders with overlapping histological features. AIM: To evaluate selected clinical and histological parameters in colonic biopsy specimens for their ability to discriminate between Crohn's disease and intestinal tuberculosis. METHODS: 25 patients with Crohn's disease and 18 patients with intestinal tuberculosis were selected for this study on the basis of established clinical, radiological and histological criteria. Clinical data and selected histological parameters in colonoscopic biopsy specimens were assessed retrospectively. A total of 103 and 41 biopsy sites were evaluated in patients with Crohn's disease and intestinal tuberculosis, respectively. RESULTS: Clinical parameters helpful in differentiating intestinal tuberculosis from Crohn's disease included chest radiographic features of tuberculosis (56% v 0%), perianal fistulae (0% v 40%) and extraintestinal manifestations of Crohn's disease (0% v 40%). Histopathological features that seemed to reliably differentiate between intestinal tuberculosis and Crohn's disease included confluent granulomas, > or =10 granulomas per biopsy site and caseous necrosis (in biopsy samples of 50%, 33% and 22% of patients with intestinal tuberculosis, respectively, v 0% of patients with Crohn's disease). Features that were observed more often in patients with intestinal tuberculosis than in those with Crohn's disease included granulomas exceeding 0.05 mm(2) (67% v 8%), ulcers lined by conglomerate epithelioid histiocytes (61% v 8%) and disproportionate submucosal inflammation (67% v 10%). CONCLUSION: Clinical features and selected histological parameters in colonoscopic biopsy specimens can help in differentiating between Crohn's disease and intestinal tuberculosis.

Adolescent↗
PubMed2006

Chiral-selective aminoacylation of an RNA minihelix: Mechanistic features and chiral suppression.

Aminoacylation of RNA minihelices is speculated to be a key step in the transition from the putative RNA world to the theater of proteins. This reaction affords the opportunity to make chiral selection of an l- or d-amino acid and thus determine the ultimate chirality that is incorporated into proteins. Previous work showed chiral preference of aminoacylation with a nonprotein, nonribozyme, RNA-directed aminoacylation system. This preference was, in turn, determined by the preexisting chirality of the RNA. The alpha-amino group attached to the asymmetric alpha-carbon of the amino acid was an obvious candidate to play a role in chiral selectivity through interactions with the RNA. Also not clear was whether a simple manipulation could change the chiral selectivity, thereby giving insight into the basis of chiral selection in the first place. Here we show, surprisingly, no role for the free alpha-amino group in chiral selection. However, by a sequence manipulation, chiral preference was suppressed and partly reversed. This result and those with further RNA constructs support the idea that the chiral preference for an l-amino acid in these constructs depends on avoiding a sugar-pucker-sensitive steric clash between a pendant group of a base with the amino acid side chain.

Amino Acids↗
PubMed2006

The use of 3D surface fitting for robust polyp detection and classification in CT colonography.

In this paper we describe the development of a computationally efficient computer-aided detection (CAD) algorithm based on the evaluation of the surface morphology that is employed for the detection of colonic polyps in computed tomography (CT) colonography. Initial polyp candidate voxels were detected using the surface normal intersection values. These candidate voxels were clustered using the normal direction, convexity test, region growing and Gaussian distribution. The local colonic surface was classified as polyp or fold using a feature normalized nearest neighborhood classifier. The main merit of this paper is the methodology applied to select the robust features derived from the colon surface that have a high discriminative power for polyp/fold classification. The devised polyp detection scheme entails a low computational overhead (typically takes 2.20min per dataset) and shows 100% sensitivity for phantom polyps greater than 5mm. It also shows 100% sensitivity for real polyps larger than 10mm and 91.67% sensitivity for polyps between 5 to 10mm with an average of 4.5 false positives per dataset. The experimental data indicates that the proposed CAD polyp detection scheme outperforms other techniques that identify the polyps using features that sample the colon surface curvature especially when applied to low-dose datasets.

Algorithms↗
PubMed2003

Near infrared spectroscopy for cost effective screening of foliar oil characteristics in a Melaleuca cajuputi breeding population.

The identification of Melaleuca cajuputi leaf samples (trees) that demonstrate enhanced oil characteristics using near infrared (NIR) spectroscopy is described. Leaf samples from an unthinned M. cajuputi seedling seed orchard in Indonesia were collected and air-dried, and their 1,8-cineole content and oil concentrations were determined. NIR spectra of the leaves were obtained, and calibrations for 1,8-cineole content and oil concentration were developed using spectra that had been selected using spectral features; that is, no knowledge of 1,8-cineole content or oil concentration was used to select the calibration samples. The calibrations were used to predict the 1,8-cineole content and oil concentration of the remaining samples. It was demonstrated that NIR spectroscopy could be used to identify leaf samples that had high 1,8-cineole contents and oil concentrations. The technique has the potential to greatly reduce the time involved in ranking large numbers of samples for these attributes, as is a requirement in tree breeding programs to enhance oil production.

Calibration↗
PubMed2006

Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans.

Recent large-scale genomic and evolutionary studies have revealed the small but detectable signature of weak selection on synonymous mutations during mammalian evolution, likely acting at the level of translational efficacy (i.e., translational selection). To investigate whether weak selection, and translational selection in particular, plays any role in shaping the fate of synonymous mutations that are present today in human populations, we studied genetic variation at the polymorphic level and patterns of evolution in the human lineage after human-chimpanzee separation. We find evidence that neutral mechanisms are influencing the frequency of polymorphic mutations in humans. Our results suggest a recent increase in mutational tendencies toward AT, observed in all isochores, that is responsible for AT mutations segregating at lower frequencies than GC mutations. In all, however, changes in mutational tendencies and other neutral scenarios are not sufficient to explain a difference between synonymous and noncoding mutations or a difference between synonymous mutations potentially advantageous or deleterious under a translational selection model. Furthermore, several estimates of selection intensity on synonymous mutations all suggest a detectable influence of weak selection acting at the level of translational selection. Thus, random genetic drift, recent changes in mutational tendencies, and weak selection influence the fate of synonymous mutations that are present today as polymorphisms. All of these features, neutral and selective, should be taken into account in evolutionary analyses that often assume constancy of mutational tendencies and complete neutrality of synonymous mutations.

Animals↗
PubMed1994

Melancholic symptom features and DSM-IV.

OBJECTIVE: The purpose of this article is to provide an overview of existing systems for the diagnosis of the endogenous (melancholic) subtype of major depression. METHOD: The authors review the critical empirical research examining this subtype and discuss its implications for DSM-IV. They examine the relationship of endogenous/melancholic symptoms to other clinical features, treatment response, selected laboratory tests, consistency across episodes, family history, and particular courses of illness. RESULTS: Melancholic symptom features are predictive of a positive response to ECT and to tricyclic antidepressants in the severely ill. Key features include psychomotor retardation, unreactive mood, pervasive anhedonia, and distinct quality of mood. Melancholic features are associated with shorter REM latency and/or nonsuppression of cortisol during the dexamethasone suppression test. Depressive episodes that are not melancholic may take on melancholic features with repetition and passage of time in some individuals. Once melancholic features are present, it is unclear whether they repeat across subsequent episodes. Melancholic features are not uniquely associated with a positive family history of depression per se, but they may be especially associated with a family history of severe depression. CONCLUSIONS: The available evidence suggests some clinical utility and some (albeit not entirely consistent) validity for the concept of melancholic features. Consequently, DSM-IV will retain the designation "with melancholic features," return to the shorter DSM-III feature listing, and broaden the designation by requiring either unreactive mood or pervasive anhedonia but not both. Further research on this subgroup is indicated.

Depressive Disorder↗
PubMed1997

Flexibility in the structure of human information processing.

The studies reported in this chapter argue for a flexible organization of higher mental processes, including perceptual and attentional systems in the visual modality and attentional systems related to action. There is electrophysiologic evidence that the visual perceptual system has a modularized structure, and that selection of perceived features is adjustable to sensory, conceptual, and utility constraints, both with respect to the hierarchy of selection cues and the transmission of information between perception and action. A distributed neural network subserves these functions and may therefore provide a source for plasticity and reorganization after brain damage by flexibility in the allocation of resources to various stages of stimulus analysis.

Cognition↗
PubMed2002

Identification of diagnostic evoked response potential segments in Alzheimer's disease.

Evoked response potentials (ERPs) to brief flashes of light were analyzed for constituent features that could be used to distinguish individuals with Alzheimer's disease (AD, n = 15) from matched control subjects (n = 17). Statistical k nearest-neighbor methods distinguished AD from control with a maximum sensitivity of 29% and false alarm rate of 12%. The comparable sensitivity/false-alarm values for a statistical projection pursuit method and an extended projection pursuit method, which selectively identify discriminative features for classification, were 75%/18% and 100%/6%, respectively. The results demonstrate that combinations of selected ERP time segments across different electrodes contain signal features that discriminate AD from control subjects with high sensitivity and specificity.

Aged↗
PubMed1996

Self-organization and competition in evolution: a conceptual problem in the use of fitness landscapes.

Recently it has been claimed that certain macroevolutionary patterns, such as the contrast between the Cambrian explosion and the Permian quiescence, can be explained as generic properties of selection processes, i.e. as features that are not caused by specific selection pressures, but that are to be expected in any selection process. The explanations are based on models of motions on randomly generated fitness landscapes, which are assumed to be representative of fitness landscapes in general. In this paper I show that such explanations of macroevolutionary patterns are conceptually flawed. If the concept of fitness used in the model is not the customary biological notion of fitness, there is no reason why organisms with higher fitness should displace organisms with lower fitness, and as a result the motion of a point representing a population is no longer determined by the shape of the fitness landscape. Nothing can be derived about the motions on the landscape, and the explanation collapses. If the model is based on the customary fitness concept, non-competing species have to be assigned the same fitnesses. As most species belonging to a radiation such as the Cambrian explosion are assumed to coexist, the majority of species will have the same fitness. A radiation of species can therefore not be modeled meaningfully on a fitness landscape.

Animals↗
PubMedDate not supplied

Computer based pattern recognition of carotid artery Doppler signals for disease classification: prospective validation.

A computer based pattern recognition method has been developed to classify the percent diameter reduction in nonoccluded internal carotid arteries. Using a combined B-mode/pulsed Doppler unit, the system utilizes spectral waveforms obtained from the low common and proximal internal carotid artery locations. The ECG-R wave is used as a time reference to synchronize the averaging of Doppler spectra from 20 heart cycles. An averaged waveform is generated and represents the spectral data from which features are extracted for analysis. A stepwise selection algorithm identifies a feature subset for partitioning the entire range of disease into two states, less than and greater than a decision point. Three such partitions are made, leading to the following categories: Normal, 1-20, 21-50 and 51-99% dia. reduction. A classifier was trained, tested prospectively against unknown data and the results compared to angiography. Of the 170 vessels tested, 141 (82%) were classified in the same category by angiography and the computer system. Agreement for each category was 93% (27/29) for the normals, 81.5% (44/54) for the 1-20% lesions, 78% (29/37) for the 21-50% lesions and 82% (41/50) for the 51-99% lesions. The computer method and angiography differed by more than one category in only one of the 170 tests. The level of agreement corrected for chance (Kappa +/- SE(K] was 0.769 +/- 0.039. Future efforts will be directed toward dividing classification of disease further (especially in the 51-99% category), developing a dedicated microprocessor for on-line analysis of the signals and using the system for prospective epidemiological studies of various populations.

Adult↗
PubMed1997

Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay: an interlaboratory study.

Experimental features of a positive selection transgenic mouse mutation assay based on a lambda lacZ transgene are considered in detail, with emphasis on results using germ cells as the target tissue. Sources of variability in the experimental protocol that can affect the statistical nature of the observations are examined, with the goal of identifying sources of excess variation in the observed mutant frequencies. The sources include plate-to-plate (within packages), package-to-package (within animals), and animal-to-animal variability. Data from five laboratories are evaluated in detail. Results suggest only scattered patterns of excess variability below the animal-to-animal level, but, generally, significant excess variability at the animal-to-animal level. Using source of variability analyses to guide the choice of statistical methods, control-vs-treatment comparisons are performed for assessing the male germ cell mutagenicity of ethylnitrosourea (ENU), isopropyl methanesulfonate (iPMS), and methyl methanesulfonate (MMS). Results on male germ cell mutagenesis of ethyl methanesulfonate (EMS) and methylnitrosourea (MNU) are also reported.

Animals↗
PubMed1983

The prognostic value of computerized tomography in comatose head-injured patients.

In a series of 121 comatose head-injured patients, computerized tomography (CT) scans were obtained at various intervals after onset of coma. The scans were classified without knowledge of previous scans or of the patient's clinical state, and predictions as to outcome at 1 year were made based on clinical features and CT findings. The state of the basal cisterns as seen on CT scans proved to be a very powerful prognosticator. Subsets of features with the greatest prognostic weight were selected systematically for CT features, clinical features, and for a combination of CT and clinical features. With these features, probability statements were made about death or survival at 1 year. The quality of the predictions was established by comparing them with actual outcome. The percentage of accurate predictions was markedly higher with a combination of clinical and CT features than with clinical or CT features alone.

Adolescent↗
PubMedDate not supplied

[A case of considerable incongruence between the expected and actual height of an individual, who was identified with methods of super-projection and comparative testing of DNA].

Anthropology is used, among others, in forensic medicine for identification of skeletal remains. The case we would like to introduce concerns the remains of an unknown man, which were subjected to identification tests in anthropological laboratory of the Forensic Medicine Department PAM. Anthropological analysis let us define the basic distinctive features, on the basis of which police selected an individual, whose features corresponded with the collected data. To confirm identity we used the super-projection method. We obtained the superposition of the estimation craniometric and cephalometric points which were suitable for, which was absolutely sufficient to regard the super-projection as successful. Comparing anthropometric features of the unknown man and appointed individual we noted considerable differences in height values. Comparative research of DNA, however, confirmed the individual's identity.

Adult↗
PubMed1995

Endoscopic management of benign airway stenosis.

Endoscopic management of benign airway stenosis is successful in the majority of patients if patients are selected properly. Predictive anatomic features have been identified that aid patient selection. Moreover, mucosal sparing techniques should be used at all times. Given its clinical effectiveness and low complication rate, endoscopic management should remain the first option for subglottic and tracheal stenosis. Endoscopic management does not preclude the use of open surgical procedures if necessary. Future studies should be directed toward refining and optimizing the endoscopic operative technique.

Adrenal Cortex Hormones↗
PubMed2006

Competition among differentiated health plans under adverse selection.

Market power and adverse selection are prevalent features of the market for pre-paid health plans. However, most of the literature on adverse selection considers extreme cases: either perfect competition or monopoly. If instead health plans are horizontally differentiated, then (i) profits derived from each low risk are higher than from each high risk and (ii) when the profits derived from each high risk are negative (cross-subsidization), a health authority as informed as the health plans can implement a Pareto-improvement. Both local and global deviations from cross-subsidization are addressed within a Nash equilibrium framework.

Economic Competition↗
PubMed2002

Visual search within and across dimensions: a case for within-dimension grouping.

We used a visual search task in which participants searched for the presence of either both members or just one member of pairs of spatially separated simple visual features. Pairs of target features could be drawn either from within the same dimension (two colours, or two orientations) or from across two different dimensions (one colour and one orientation). In Experiment 1, display items carrying target and non-target features (target and distractor items respectively) were presented at interspersed spatial locations. Reaction times (RTs) to find both of two feature targets were generally slower than to find one feature target for within- and across-dimension target pairs alike. This slowing was approximately constant across display set sizes, with one exception: for within-dimension targets, two features could be detected as fast as single features when there were just two items in displays. Experiment 2 replicated the finding across all display set sizes when target items were always spatially adjacent rather than interspersed with distractor items. We interpret these data in terms of grouping between target features within the same dimension, and argue against there being any qualitative limit on visual processing or selection when target features come from a single dimension relative to when they come from separate dimensions.

Adult↗
PubMed1995

[Emergence of cooperation in one-short prisoner's dilemmas and the role of trust].

The main purpose of this study is to apply the "selective play paradigm" to explain how cooperation emerges in one-shot prisoner's dilemmas. A unique feature of the selective play paradigm is the option for not playing a PD game. For this purpose, a computer simulation of 100-actor groups was conducted. At the beginning of each replication, each simulated actor was randomly assigned to one of eleven levels of trust, which indicates the actor's estimate of the overall cooperation rate in the group. Each simulated actor, then, decided whether or not to interact with the previous partner based on the calculated expected gains from interacting with one of the other partners. Results of the simulation show that: (1) when substantial opportunity costs exist, having a high level of trust benefits the actor; (2) the above effect of trust depends on the actor's cooperativeness in PD games; (3) but does not depend on the overall cooperation rate in the group.

Computer Simulation↗