988 resultados para Area Functional
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BACKGROUND The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. METHODS AND RESULTS A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). CONCLUSIONS In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00979199.
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Grazing ungulates play a key role in many ecosystems worldwide and can form diverse assemblages, such as in African savannahs. In many of these ecosystems, present-day ungulate communities are impoverished subsets of once diverse assemblages. While we know that excluding all ungulates from grasslands can exert major effects on both the structure and composition of the vegetation, how different individual ungulate species may have contrasting effects on grassland communities remains poorly understood. Here, we performed a long-term ‘Russian doll’ grazing exclosure experiment in an African savannah to test for the effects of different size classes of grazers on grassland structure and composition. At five sites, grazer species of decreasing size class (ranging from white rhino to scrub hare) were excluded using four fence types, to experimentally create different realized grazer assemblages. The vegetation structure and the grass functional community composition were characterized in 6 different years over a 10-year period. Additionally, animal footprints were counted to quantify the abundance of different ungulate species in each treatment. We found that while vegetation height was mostly driven by total grazing pressure of all species together, ungulate community composition best explained the functional community composition of grasses. In the short term, smaller ungulate species (‘mesoherbivores’) had strongest effects on vegetation composition, by shifting communities towards dominance by species with low specific leaf area and low nutritional value. In the long term, large grazers had stronger but similar effects on the functional composition of the system. Surprisingly, the largest ‘mega-herbivore’, the white rhinoceros, did not have strong effects on the vegetation structure or composition. Synthesis. Our results support the idea that different size classes of grazers have varying effects on the functional composition of grassland plant communities. Therefore, the worldwide decline in the diversity of ungulate species is expected to have (had) major impacts on community composition and functioning of grassland ecosystems, even if total grazing pressure has remained constant, for example, due to replacement by livestock.
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Identifying and characterizing the genes responsible for inherited human diseases will ultimately lead to a more holistic understanding of disease pathogenesis, catalyze new diagnostic and treatment modalities, and provide insights into basic biological processes. This dissertation presents research aimed at delineating the genetic and molecular basis of human diseases through epigenetic and functional studies and can be divided into two independent areas of research. The first area of research describes the development of two high-throughput melting curve based methods to assay DNA methylation, referred to as McMSP and McCOBRA. The goal of this project was to develop DNA methylation methods that can be used to rapidly determine the DNA methylation status at a specific locus in a large number of samples. McMSP and McCOBRA provide several advantages over existing methods, as they are simple, accurate, robust, and high-throughput making them applicable to large-scale DNA methylation studies. McMSP and McCOBRA were then used in an epigenetic study of the complex disease Ankylosing spondylitis (AS). Specifically, I tested the hypothesis that aberrant patterns of DNA methylation in five AS candidate genes contribute to disease susceptibility. While no statistically significant methylation differences were observed between cases and controls, this is the first study to investigate the hypothesis that epigenetic variation contributes to AS susceptibility and therefore provides the conceptual framework for future studies. ^ In the second area of research, I performed experiments to better delimit the function of aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), which when mutated causes various forms of inherited blindness such as Leber congenital amaurosis. A yeast two-hybrid screen was performed to identify putative AIPL1-interacting proteins. After screening 2 × 106 bovine retinal cDNA library clones, 6 unique putative AIPL1-interacting proteins were identified. While these 6 AIPL1 protein-protein interactions must be confirmed, their identification is an important step in understanding the functional role of AIPL1 within the retina and will provide insight into the molecular mechanisms underlying inherited blindness. ^
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The smallest marine phytoplankton, collectively termed picophytoplankton, have been routinely enumerated by flow cytometry since the late 1980s, during cruises throughout most of the world ocean. We compiled a database of 40,946 data points, with separate abundance entries for Prochlorococcus, Synechococcus and picoeukaryotes. We use average conversion factors for each of the three groups to convert the abundance data to carbon biomass. After gridding with 1° spacing, the database covers 2.4% of the ocean surface area, with the best data coverage in the North Atlantic, the South Pacific and North Indian basins. The average picophytoplankton biomass is 12 ± 22 µg C L-1 or 1.9 g C m-2. We estimate a total global picophytoplankton biomass, excluding N2-fixers, of 0.53 - 0.74 Pg C (17 - 39 % Prochlorococcus, 12 - 15 % Synechococcus and 49 - 69 % picoeukaryotes). Future efforts in this area of research should focus on reporting calibrated cell size, and collecting data in undersampled regions.
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This paper presents a new tool for large-area photo-mosaicking (LAPM tool). This tool was developed specifically for the purpose of underwater mosaicking, and it is aimed at providing end-user scientists with an easy and robust way to construct large photo-mosaics from any set of images. It is notably capable of constructing mosaics with an unlimited number of images on any modern computer (minimum 1.30 GHz, 2 GB RAM). The mosaicking process can rely on both feature matching and navigation data. This is complemented by an intuitive graphical user interface, which gives the user the ability to select feature matches between any pair of overlapping images. Finally, mosaic files are given geographic attributes that permit direct import into ArcGIS. So far, the LAPM tool has been successfully used to construct geo-referenced photo-mosaics with photo and video material from several scientific cruises. The largest photo-mosaic contained more than 5000 images for a total area of about 105,000 m**2. This is the first article to present and to provide a finished and functional program to construct large geo-referenced photo-mosaics of the seafloor using feature detection and matching techniques. It also presents concrete examples of photo-mosaics produced with the LAPM tool.
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Arctic vegetation is characterized by high spatial variability in plant functional type (PFT) composition and gross primary productivity (P). Despite this variability, the two main drivers of P in sub-Arctic tundra are leaf area index (LT) and total foliar nitrogen (NT). LT and NT have been shown to be tightly coupled across PFTs in sub-Arctic tundra vegetation, which simplifies up-scaling by allowing quantification of the main drivers of P from remotely sensed LT. Our objective was to test the LT-NT relationship across multiple Arctic latitudes and to assess LT as a predictor of P for the pan-Arctic. Including PFT-specific parameters in models of LT-NT coupling provided only incremental improvements in model fit, but significant improvements were gained from including site-specific parameters. The degree of curvature in the LT-NT relationship, controlled by a fitted canopy nitrogen extinction co-efficient, was negatively related to average levels of diffuse radiation at a site. This is consistent with theoretical predictions of more uniform vertical canopy N distributions under diffuse light conditions. Higher latitude sites had higher average leaf N content by mass (NM), and we show for the first time that LT-NT coupling is achieved across latitudes via canopy-scale trade-offs between NM and leaf mass per unit leaf area (LM). Site-specific parameters provided small but significant improvements in models of P based on LT and moss cover. Our results suggest that differences in LT-NT coupling between sites could be used to improve pan-Arctic models of P and we provide unique evidence that prevailing radiation conditions can significantly affect N allocation over regional scales.
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The proportion of elderly people in the population has increased rapidly in the last century and consequently "healthy aging" is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve. 21 subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of cognitive reserve; one group comprised subjects with high cognitive reserve (9 members) and the other contained those with low cognitive reserve (12 members). To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG) while they performed a memory task (modified version of the Sternberg¿s Task). We then applied two algorithms (Phase Locking Value & Phase-Lag Index) to study the dynamics of functional connectivity. In response to the same task, the subjects with lower cognitive reserve presented higher functional connectivity than those with higher cognitive reserve. These results may indicate that participants with low cognitive reserve needed a greater 'effort' than those with high cognitive reserve to achieve the same level of cognitive performance. Therefore, we conclude that cognitive reserve contributes to the modulation of the functional connectivity patterns of the aging brain.
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Dynamic blood oxygenation level-dependent functional MRI was applied at 7 T in the rat olfactory bulb (OB) with pulsed delivery of iso-amyl acetate (IAA) and limonene. Acquisition times for single-slice and whole OB data were 8 and 32 s, respectively, with spatial resolution of 220 × 220 × 250 μm. On an intrasubject basis, short IAA exposures of 0.6 min separated by 3.5-min intervals induced reproducible spatial activity patterns (SAPs) in the olfactory nerve layer, glomerular layer, and external plexiform layer. During long exposures (≈10 min), the initially dominant dorsal SAPs declined in intensity and area, whereas in some OB regions, the initially weak ventral/lateral SAPs increased first and then decreased. The SAPs of different concentrations were topologically similar, which implies that whereas an odor at various concentrations activates the same subsets of receptor cells, different concentrations are assessed and discriminated by variable magnitudes of laminarspecific activations. IAA and limonene reproducibly activated different subsets of receptor cells with some overlaps. Whereas qualitative topographical agreement was observed with results from other methods, the current dynamic blood oxygenation level-dependent functional MRI results can provide quantitative SAPs of the entire OB.
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Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.
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At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography and magnetic resonance imaging. The signal used by positron emission tomography is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. Because the changes in blood flow are accompanied by lesser changes in oxygen consumption, local changes in brain oxygen content occur at the sites of activation and provide the basis for the signal used by magnetic resonance imaging. The biological basis for these signals is now an area of intense research stimulated by the interest in these tools for cognitive neuroscience research.
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Human area V1 offers an excellent opportunity to study, using functional MRI, a range of properties in a specific cortical visual area, whose borders are defined objectively and convergently by retinotopic criteria. The retinotopy in V1 (also known as primary visual cortex, striate cortex, or Brodmann’s area 17) was defined in each subject by using both stationary and phase-encoded polar coordinate stimuli. Data from V1 and neighboring retinotopic areas were displayed on flattened cortical maps. In additional tests we revealed the paired cortical representations of the monocular “blind spot.” We also activated area V1 preferentially (relative to other extrastriate areas) by presenting radial gratings alternating between 6% and 100% contrast. Finally, we showed evidence for orientation selectivity in V1 by measuring transient functional MRI increases produced at the change in response to gratings of differing orientations. By systematically varying the orientations presented, we were able to measure the bandwidth of the orientation “transients” (45°).
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The effects of practice on the functional anatomy observed in two different tasks, a verbal and a motor task, are reviewed in this paper. In the first, people practiced a verbal production task, generating an appropriate verb in response to a visually presented noun. Both practiced and unpracticed conditions utilized common regions such as visual and motor cortex. However, there was a set of regions that was affected by practice. Practice produced a shift in activity from left frontal, anterior cingulate, and right cerebellar hemisphere to activity in Sylvian-insular cortex. Similar changes were also observed in the second task, a task in a very different domain, namely the tracing of a maze. Some areas were significantly more activated during initial unskilled performance (right premotor and parietal cortex and left cerebellar hemisphere); a different region (medial frontal cortex, “supplementary motor area”) showed greater activity during skilled performance conditions. Activations were also found in regions that most likely control movement execution irrespective of skill level (e.g., primary motor cortex was related to velocity of movement). One way of interpreting these results is in a “scaffolding-storage” framework. For unskilled, effortful performance, a scaffolding set of regions is used to cope with novel task demands. Following practice, a different set of regions is used, possibly representing storage of particular associations or capabilities that allow for skilled performance. The specific regions used for scaffolding and storage appear to be task dependent.
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Recent evidence emerging from several laboratories, integrated with new data obtained by searching the genome databases, suggests that the area code hypothesis provides a good heuristic model for explaining the remarkable specificity of cell migration and tissue assembly that occurs throughout embryogenesis. The area code hypothesis proposes that cells assemble organisms, including their brains and nervous systems, with the aid of a molecular-addressing code that functions much like the country, area, regional, and local portions of the telephone dialing system. The complexity of the information required to code cells for the construction of entire organisms is so enormous that we assume that the code must make combinatorial use of members of large multigene families. Such a system would reuse the same receptors as molecular digits in various regions of the embryo, thus greatly reducing the total number of genes required. We present the hypothesis that members of the very large families of olfactory receptors and vomeronasal receptors fulfill the criteria proposed for area code molecules and could serve as the last digits in such a code. We discuss our evidence indicating that receptors of these families are expressed in many parts of developing embryos and suggest that they play a key functional role in cell recognition and targeting not only in the olfactory system but also throughout the brain and numerous other organs as they are assembled.
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Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings. (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex, another area displays decreased signal intensity upon stimulation.
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In this study, we implement chronic optical imaging of intrinsic signals in rat barrel cortex and repeatedly quantify the functional representation of a single whisker over time. The success of chronic imaging for more than 1 month enabled an evaluation of the normal dynamic range of this sensory representation. In individual animals for a period of several weeks, we found that: (i) the average spatial extent of the quantified functional representation of whisker C2 is surprisingly large--1.71 mm2 (area at half-height); (ii) the location of the functional representation is consistent; and (iii) there are ongoing but nonsystematic changes in spatiotemporal characteristics such as the size, shape, and response amplitude of the functional representation. These results support a modified description of the functional organization of barrel cortex, where although a precisely located module corresponds to a specific whisker, this module is dynamic, large, and overlaps considerably with the modules of many other whiskers.