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Endoscopy: current state and future trends in tumor diagnosis.

Gastrointestinal endoscopy has been significantly improved during the last decade. Tumors of less than 5 mm in diameter can now be detected by using high-resolution videoendoscopes. Additional in vivo staining allows better delineation and more precise identification of the lateral spreading of lesions. Today the missing of cancers in early stage is mainly due to lack of screening programs rather than technical limitations. Endoscopic mucosal resection of superficial lesions is primarily a diagnostic procedure to determine the need for surgery. However, it may be curative when histology proves a complete resection. Swallowable endoscopy capsules provide access to the entire small bowel. The capsule takes 2 images/second and transmits them to a recorder. After passage of the small bowel the 50,000 recorded images are reviewed on a computer. The capsule should not be used in patients with suspected intestinal stenosis. Endoscopic ultrasound (EUS) is an established procedure for the T- and N-staging of gastrointestinal tumors. With an accuracy rate of around 90%, this method is helpful for the therapeutic decision e.g. indication for operation. EUS cannot distinguish benign from malignant changes, particularly in focal pancreatic lesions. However, this drawback can be reduced with EUS-guided fine-needle aspiration cytology of the primary lesion or an accessible lymph node. At 7.5-20 MHz the gastrointestinal wall is visualized in 5 and more layers allowing for detailed staging of T1 tumors. 3D-EUS resolution is described to be better than 100 microns. Optical coherence tomography (OCT) with a resolution of 10-20 microns demonstrates tissue micro-architecture. Structures only seen in histology before are visualized real-time in vivo during endoscopy. However, the infiltration depth is only 1 mm and the method is still in the clinical experimental stage. Confocal microscopy has been recently adapted for endoscopy. Images from the first clinical evaluations already show single cells and nuclei. Cellular characteristics become visible and endoscopy is on the way towards optical biopsy.

Endoscopy, Gastrointestinal↗

Conversation analysis of communication breakdown after closed head injury.

This single case study investigated the use of Conversation Analysis (CA) in assessing pragmatic language difficulties after closed head injury (CHI). The aim was to see if CA captures the types of communication breakdown observed after CHI and whether results from CA can be directly related to scores on formal tests more typically applied after CHI. The results suggested that CA was a sensitive tool for identifying and investigating pragmatic deficits in this case. It facilitated an exploration of whether language impairments identified on formal tests manifest themselves in functional communication; it revealed how different interlocutors adapt to these language difficulties in conversation and also explained why some conversational partners were more successful than others. Considered together, formal test results and CA insights facilitated an in-depth analysis into the precise nature of the communicative impairments of the speaker in this exploratory study, suggesting that CA is a promising approach to the assessment of pragmatic impairments in the CHI population.

Adaptation, Psychological↗

Occlusal caries formation in vitro: comparison of resin-modified glass ionomer with fluoride-releasing sealant.

The purpose of this laboratory study was to evaluate caries-like lesion formation in occlusal enamel adjacent to a light-cured resin-modified glass ionomer utilized as a pit and fissure sealant and a conventional light-cured, fluoride-releasing sealant. Fluoride-free prophylaxis was done on occlusal surfaces of 12 caries-free mandibular molar teeth that had not been exposed to the oral cavity. Occlusal surface morphology was examined by SEM on the uncoated specimens. Each tooth was then sectioned into 2 portions buccolingually, producing mesial and distal tooth halve. Occlusal surfaces of mesial tooth halves were prepared for an experimental light-cured resin-modified glass ionomer (RMG) sealant (PH-SE II, ESPE), and for comparison, a light-cured fluoride-releasing pit and fissure (PFS) sealant (Helioseal F, Ivoclar) was placed on occlusal surfaces of the corresponding distal tooth halves. The sealed occlusal surfaces were examined uncoated by SEM to compare RMG and PFS adaptation. After thermocycling in artificial saliva, caries-like lesions were formed in the occlusal surfaces adjacent to RMG and PFS. Longitudinal sections were taken for comparison of lesion formation adjacent to RMG and PFS. Mean lesion depths in occlusal surfaces were 64 +/- 17 mm for RMG, and 116 +/- 27 mm for PFS (p < 0.05, paired t-test). Occlusal lesions terminated at the point where bonding occurred between the occlusal enamel and RMG or PFS. SEM surface topography demonstrated adequate adaptation of the materials with obliteration of the typical pit and fissure surface morphology by both RMG and PFS. While both the resin-modified glass ionomer and fluoride-releasing sealant materials protected the pit and fissure enamel from caries development, the resin-modified glass ionomer reduced the extent of caries involvement in the adjacent unsealed occlusal incline enamel, when compared with the resin sealant.

Bisphenol A-Glycidyl Methacrylate↗

Patterns of violence in homeless women.

Fifty percent of all women in America have reported being battered at some point in time, and one in five report regular assaults. This exploratory qualitative study's purpose was to describe reported patterns of violence in sheltered battered women. Homelessness was the adaptive response to battering. A purposive sample of 7 women described violence patterns from childhood and their most recent relationships prior to seeking shelter. In-depth audiotaped interviews indicated extreme violence and terror. Thematic analysis revealed an understanding of abusive patterns with a male partner. A theory of freedom-seeking behavior emerged, with related themes including terror, murderous thoughts, awakening, and escape. The emerging theory has implications for outreach, case finding, and identification of intervention timing for abused women.

Adaptation, Psychological↗

Effect of gingival fluid on marginal adaptation of Class II resin-based composite restorations.

PURPOSE: To evaluate in vitro the marginal quality of Class II composite restorations at the gingival enamel margins as affected by contamination of the cavities with gingival fluid (GF) during different steps of resin bonding procedures. MATERIALS AND METHODS: 70 Class II cavities were prepared in extracted human molars and restored with composite using a multi-component bonding system (OptiBond FL/Herculite XRV; OPTI) or a single-bottle adhesive (Syntac Sprint/Tetric Ceram; SYN). The cavities were contaminated with human GF: C1 after acid etching, C2 after application of the primer (OPTI) or light-curing of the primer-adhesive (SYN), and C3 after light-curing of the resin adhesive (OPTI). Uncontaminated cavities were used as the control (C0). The restored teeth were subjected to thermocycling (TC) and replicated for SEM analysis of marginal gap formation. Microleakage at the gingival margins was determined by dye penetration with basic fuchsin. STATISTICS: non-parametric tests (Kruskal-Wallis test, Mann-Whitney test with Bonferroni correction). RESULTS: In both bonding systems, contamination with GF after acid etching (C1) did not impair the marginal quality; the mean percentages of continuous margin/mean depths of dye penetration were: OPTI: C0: 88.5%/0.10 mm, C1: 95.6%/0.04 mm; SYN: C0: 90.9%/0.08 mm, C1: 97.0%/0.05 mm. Marginal adaptation was adversely affected when GF contamination was performed after

Acid Etching, Dental↗

Unusual organic osmolytes in deep-sea animals: adaptations to hydrostatic pressure and other perturbants.

Shallow-living marine invertebrates use free amino acids as cellular osmolytes, while most teleosts use almost no organic osmolytes. Recently we found unusual osmolyte compositions in deep-sea animals. Trimethylamine N-oxide (TMAO) increases with depth in muscles of some teleosts, skates, and crustaceans (up to 300 mmol/kg at 2900 m). Other deep-sea animals had high levels of (1). scyllo-inositol in echinoderms, gastropods, and polychaetes, (2). that polyol plus beta-alanine and betaine in octopods, (3). hypotaurine, N-methyltaurine, and unidentified methylamines in vestimentiferans from hydrothermal vents and cold seeps, and (4). a depth-correlated serine-phosphate osmolyte in vesicomyid clams from trench seeps. We hypothesize that some of these solutes counteract effects of hydrostatic pressure. With lactate dehydrogenase, actin, and pyruvate kinase, 250 mM TMAO (but not glycine) protected both ligand binding and protein stability against pressure. To test TMAO in living cells, we grew yeast under pressure. After 1 h at 71 MPa, 3.5 h at 71 MPa, and 17 h at 30 MPa, 150 mM TMAO generally doubled the number of cells that formed colonies. Sulfur-based osmolytes which are not correlated with depth, such as hypotaurine and thiotaurine, are probably involved in sulfide metabolism and detoxification. Thus deep-sea osmolytes may have at least two other roles beyond acting as simple compatible osmotica.

Adaptation, Physiological↗

Adaptation to jejunoileal bypass promotes experimental colorectal carcinogenesis.

The co-carcinogenic potential of 85 per cent jejunoileal bypass (JIB) was tested in male Sprague-Dawley rats (n = 81) given 6 preliminary injections of the selective intestinal carcinogen azoxymethane (total dose 90 mg/kg). Controls had sham JIB. Colorectal adaptation was studied 30 weeks postoperatively in rats given injections of vehicle alone. JIB caused 17-33 per cent increments in colonic length, weight and crypt depth; crypt cell production rate was more than doubled (P less than 0.01). Despite lowering body weight by 27 per cent, JIB increased the median number of colorectal tumours per rat from 3 to 8 (P less than 0.01). The findings suggest that evidence of hyperplasia and dysplasia should be sought in patients receiving subtotal jejunoileal bypass for obesity.

Adaptation, Physiological↗

Comparative genomics reveals genotype-phenotype concordance and cryptic resistomes in clinical Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen because of its adaptability. It shows rapid evolution of multidrug resistance (MDR). Phenotype-based diagnostics often fail to detect silent resistance determinants and early adaptive changes. This study integrates phenotypic profiling with whole-genome sequencing (WGS) to examine resistance architecture in clinical isolates from eastern India. METHODS: From 1295 culture-positive P. aeruginosa specimens collected at a tertiary care hospital in eastern India. Using predefined criteria, representative MDR and non-MDR isolates were selected, including distinct resistance phenotypes, specimen-source diversity, and hospital and community-acquired settings; multivariate analysis of resistance profiles illustrated phenotypic diversity. Antimicrobial susceptibility assessed using VITEK-2 and Kirby-Bauer disk diffusion, species identity confirmed by 16&#xa0;S rRNA sequencing, and genomic analysis processed through a reference-guided workflow. Antimicrobial Resistance (AMR) determinants were identified through CARD, and phylogenetic tree constructed from 454 publicly available P. aeruginosa genomes. RESULTS: MDR exhibited greater sequence divergence relative to PA14 (~&#x2009;69,000 variants) than the non-MDR isolate (~&#x2009;58,700 variants), with >&#x2009;92% coverage at &#x2265;&#x2009;30X depth. Strong genotype-phenotype concordance observed in MDR isolates across five antibiotic classes, associated with &#x3b2;-lactamase variants (PDC-67, OXA-396) and regulatory adaptations (ArmR, cprS). The non-MDR isolate harboured gyrA (T83I) resistance-associated mutations, PDC-1, and OXA-847 without phenotypic expression, indicating silent resistome. Phylogenetically, MDR isolates clustered tightly within the phylogeny, while the non-MDR isolate formed a distinct lineage. CONCLUSION: Observed genomic differences align with adaptation under antimicrobial selection, though confirmation requires larger collections. The non-MDR isolate retained a silent resistome. Findings highlight limitations of phenotype-only diagnostics, support genomic data integration, and emphasize transcriptomics for hidden resistance expression and regulatory dynamics.

Pseudomonas aeruginosa↗

Ascent exhalations of Antarctic fur seals: a behavioural adaptation for breath-hold diving?

Novel observations collected from video, acoustic and conductivity sensors showed that Antarctic fur seals consistently exhale during the last 50-85% of ascent from all dives (10-160 m, n > 8000 dives from 50 seals). The depth of initial bubble emission was best predicted by maximum dive depth, suggesting an underlying physical mechanism. Bubble sound intensity recorded from one seal followed predictions of a simple model based on venting expanding lung air with decreasing pressure. Comparison of air release between dives, together with lack of variation in intensity of thrusting movement during initial descent regardless of ultimate dive depth, suggested that inhaled diving lung volume was constant for all dives. The thrusting intensity in the final phase of ascent was greater for dives in which ascent exhalation began at a greater depth, suggesting an energetic cost to this behaviour, probably as a result of loss of buoyancy from reduced lung volume. These results suggest that fur seals descend with full lung air stores, and thus face the physiological consequences of pressure at depth. We suggest that these regular and predictable ascent exhalations could function to reduce the potential for a precipitous drop in blood oxygen that would result in shallow-water blackout.

Adaptation, Physiological↗

Is neural filling-in necessary to explain the perceptual completion of motion and depth information?

Retinal activity is the first stage of visual perception. Retinal sampling is non-uniform and not continuous, yet visual experience is not characterized by holes and discontinuities in the world. How does the brain achieve this perceptual completion? Fifty years ago, it was suggested that visual perception involves a two-stage process of (i) edge detection followed by (ii) neural filling-in of surface properties. We examine whether this general hypothesis can account for the specific example of perceptual completion of a small target surrounded by dynamic dots (an 'artificial scotoma'), a phenomenon argued to provide insight into the mechanisms responsible for perception. We degrade the target's borders using first blur and then depth continuity, and find that border degradation does not influence time to target disappearance. This indicates that important information for the continuity of target perception is conveyed at a coarse spatial scale. We suggest that target disappearance could result from adaptation that is not specific to borders, and question the need to hypothesize an active filling-in process to explain this phenomenon.

Depth Perception↗

Origin of the electroretinogram in the intact macaque eye--I. Principal component analysis.

Responses to 400 msec flashes of white light were recorded at various depths in the retina of the intact macaque eye. A statistical technique, principal component analysis (PCA), was used to isolate independent components from the LERG, using the changing contribution of a cell's response to the LERG with retinal depth. Two approaches were evaluated: first, PCA was performed on the complete LERG waveforms and, second, on small sections of the LERG. The first method yielded a component strongly resembling the receptor response, apart from some inconsistencies in the proximal layers, and a component in which the b-wave was the most prominent feature, but which still contained some other responses. Hence, the components were not suitable to describe the LERG in terms of responses of specific cell types. The second method uses PCA to determine whether or not the potential change within a small time window is accounted for by a single component. This method, which essentially uses the knowledge that different cell types respond with different delay times, yielded three components. These were identified as the receptor component, the b-wave and the d.c.-component. The voltage-depth profiles of these components were assessed.

Animals↗

Construction and visualisation of three-dimensional facial statistics.

This paper presents a new method for the construction of three-dimensional (3D) probabilistic facial averages and demonstrates the potential for applications in clinical craniofacial research and patient assessment. Averages are constructed from a database of registered laser-range scans and photographic images using feature based image warping. Facial features are extracted using a template of connected contours, adapted to each subject interactively using snakes. Each subject's images are warped to the average template shape and the mean depth, colour and covariance matrix is found at each point. Statistical comparison of individuals with an average or between two averages is visualised by converting the probabilities to a coloured texture map.

Adult↗

Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells.

Downregulation of proapoptotic molecules like Fas or caspase 8, or upregulation of antiapoptotic molecules like FLICE inhibitory protein has been suggested to be a regulatory mechanism set up by tumor cells to block the death signal received via death receptors. In an in-depth study of the Fas/FasL-signaling pathway in thyroid tumor development, we have demonstrated that tumor cells specifically downregulate the multideath receptor adapter Fas-associated death domain (FADD). The regulation of FADD expression occurred only at the protein level. Furthermore, in the absence of FADD, Fas-signaling resulted in accelerated growth of thyrocytes. Since thyrocytes also acquired FasL expression during tumor development, the absence of FADD protein could lead to greater resistance to numerous death receptor-mediated apoptosis, stimulation of their own proliferation through Fas/FasL interaction, and the capacity to counter-attack the infiltrating lymphocytes.

Adaptor Proteins, Signal Transducing↗

To what extent is the foraging behaviour of aquatic birds constrained by their physiology?

Aquatic birds have access to limited amounts of usable oxygen when they forage (dive) underwater, so the major physiological constraint to their behaviour is the need to periodically visit the water surface to replenish these stores and remove accumulated carbon dioxide. The size of the oxygen stores and the rate at which they are used (V dot o2) or carbon dioxide accumulates are the ultimate determinants of the duration that aquatic birds can remain feeding underwater. However, the assumption that the decision to terminate a dive is governed solely by the level of the respiratory stores is not always valid. Quantification of an optimal diving model for tufted ducks (Aythya fuligula) shows that while they dive efficiently by spending a minimum amount of time on the surface to replenish the oxygen used during a dive, they dive with nearly full oxygen stores and surface well before these stores are exhausted. The rates of carbon dioxide production during dives and removal during surface intervals are likely to be at least as important a constraint as oxygen; thus, further developments of optimal diving models should account for their effects. In the field, diving birds will adapt to changing environmental conditions and often maximise the time spent submerged during diving bouts. However, other factors influence the diving depths and durations of aquatic birds, and in some circumstances they are unable to forage sufficiently well to provide food for their offspring. The latest developments in telemetry have demonstrated how diving birds can make physiological decisions based on complex environmental factors. Diving penguins can control their inhaled air volume to match the expected depth, likely prey encounter rate, and buoyancy challenges of the following dive.

Animals↗

Range modulation in proton therapy--an optimization technique for clinical and experimental applications.

A fast optimization algorithm for range modulation in clinical and experimental applications of proton therapy is described. The method is versatile towards the number of parameters provided for range modulation, i.e. the trade-off between accuracy and simplicity of the latter can be chosen freely. The approach is, therefore, adaptable to most operating proton therapy facilities. It requires only a few basic measurements as input data and results in a depth dose uniformity of better than 2%. A typical calculation takes less than 90 s on a DEC VAXstation 3100, FORTRAN. The method has been extensively tested at the TRIUMF Proton Therapy Facility in Vancouver, BC.

Algorithms↗

Artificial intelligence methods for theory representation and hypothesis formation.

This article describes artificial intelligence methods for representing theories in molecular biology, and for improving the predictive power of these theories using experimental data. A program called GENSIM provides a framework for representing theories that includes descriptions of classes of biological objects (genes, enzymes, etc.), and processes that specify potential interactions among these objects (such as enzymatic reactions). GENSIM can employ a theory specified within this framework to predict the outcomes of biological experiments. A program called HYPGENE comes into play when the observed outcome of an experiment does not match the outcome predicted by GENSIM. HYPGENE works backward from the error in GENSIMs prediction to postulate changes to both the theory embodied by GENSIM, and the presumed initial conditions of the experiment. I view HYPGENEs hypothesis generation task as a design problem, and I have adapted AI methods developed for design and planning to this task. These techniques were developed in conjunction with an in-depth study of the discovery of the gene regulation mechanism of attenuation in the E. coli tryptophan operon. Both GENSIM and HYPGENE have been tested on sample problems from the history of attenuation, and produced many of the same solutions as biologists did.

Artificial Intelligence↗

Imaging and quantification of calcified corneal lesions with optical coherence tomography.

PURPOSE: The purpose of this study was to image and quantify calcified corneal lesions with optical coherence tomography (OCT) and to evaluate this diagnostic method to assess this corneal disease. METHODS: In a clinical study 15 eyes of 14 patients with calcified corneal lesions in the anterior portions of the cornea were assessed with slit-lamp biomicroscopy and slit-lamp-adapted OCT. The qualitative and quantitative optical changes were compared with the clinical findings. RESULTS: In corneal OCT all calcified lesions revealed marked hyperreflective changes that correlated well with macroscopic findings. Dense calcified lesions resulted in partial or complete shadowing of the posterior corneal structures. The thickness values for the hyperreflective calcified lesions ranged from 27 to 344 microm. CONCLUSION: Noncontact slit-lamp-adapted OCT may be of value in assessing calcified corneal lesions. Corneal OCT could also be used to precisely measure the depth of these corneal processes and evaluate treatment modalities.

Adolescent↗

Genetically based phenotype-environment association for swimming behavior in lake whitefish ecotypes (Coregonus clupeaformis Mitchill).

Studies of phenotype-environment associations in adaptive radiation have focused largely on morphological traits related to resource-based phenotypic differences. The genetic basis of adaptive behaviors implicated in population divergence remains poorly understood, as few studies have tested the hypothesis of behavioral phenotype-environment associations. We provide evidence of a phenotype-environment association for differential adaptive swimming behaviors through experiments conducted on dwarf, normal, and hybrid lake whitefish (Coregonus clupeaformis). Highly significant differences were observed for depth selection, directional changes, and burst swimming, implicating a genetic basis for these behaviors. Hybrid crosses revealed that depth selection is under additive genetic control, while dominance effects were suggested for directional changes and burst swimming. Estimates for the genetic basis of behavioral differentiation from an animal model were consistent with these observations. Comparative estimates of behavioral differentiation (Q(ST)) against neutral expectations (F(ST)) revealed pronounced departures from neutral expectations in all three behavioral phenotypes, consistent with the hypothesis that directional selection has driven the divergence of behavior in dwarf and normal lake whitefish ecotypes.

Animals↗