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The geometric transfer function component for scintillation camera collimators with straight parallel holes.

A theoretical approach has been developed that allows the geometric transfer function component for conventional scintillation camera collimators to be predicted in closed form. If transfer function analysis is to be useful in describing imaging system performance, the image of a point source must not depend on source position in a plane parallel to the detection plane. This shift invariance can be achieved by analysis of system response in terms of an effective point spread function, defined as the normalised image of a point source that would be obtained if the camera collimator were uniformly translated (but not rotated) during image formation. The geometric component of the corresponding effective transfer function is shown to be expressed simply by the absolute square of the two-dimensional Fourier transform of a collimator hole aperture, with the spatial frequency plane scaled by a factor which depends on collimator length, source-to-collimator distance, and collimator-to-detection plane distance. Closed form algebraic expressions of the geometric transfer function have been obtained for all four common hold shapes (circular, hexagonal, square and triangular). Monte Carlo simulations and experimental measurements have shown these theoretical expressions to be highly accurate.

Fourier Analysis↗

Breast cancer clusters in the northeast United States: a geographic analysis.

High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.

Breast Neoplasms↗

Implicating an introduced generalist parasitoid in the invasive browntail moth's enigmatic demise.

Recent attention has focused on the harmful effects of introduced biological control agents on nontarget species. The parasitoid Compsilura concinnata is a notable example of such biological control gone wrong. Introduced in 1906 primarily for control of gypsy moth, Lymantria dispar, this tachinid fly now attacks more than 180 species of native Lepidoptera in North America. While it did not prevent outbreaks or spread of gypsy moth, we present reanalyzed historical data and experimental findings suggesting that parasitism by C. concinnata is the cause of the enigmatic near-extirpation of another of North America's most successful invaders, the browntail moth (Euproctis chrysorrhoea). From a range of approximately 160,000 km2 a century ago, browntail moth (BTM) populations currently exist only in two spatially restricted coastal enclaves, where they have persisted for decades. We experimentally established BTM populations within this area and found that they were largely free of mortality caused by C. concinnata. Experimental populations of BTM at inland sites outside of the currently occupied coastal enclaves were decimated by C. concinnata, a result consistent with our reanalysis of historical data on C. concinnata parasitism of the browntail moth. The role of C. concinnata in the disappearance of browntail moth outside these enclaves has not been reported before. Despite the beneficial role played by C. concinnata in reversing the browntail moth invasion, we do not advocate introduction of generalist biological control agents. Our findings illustrate that the impact of such organisms can be both unpredictable and far-reaching.

Animals↗

Distorted odor maps in the olfactory bulb of semaphorin 3A-deficient mice.

Semaphorin 3A (Sema3A) repels growing olfactory axons that express neuropilin-1 (NP-1), a receptor for Sema3A. The Sema3A-mediated axon guidance seems to be essential for the formation of the glomerular sensory map in the olfactory bulb (OB). To understand whether and how Sema3A is involved in sensory map formation, we examined the glomerular map in the OB of adult Sema3A-deficient mice. In wild-type mice, NP-1-positive glomeruli form the lateral and medial bands and avoid the anteromedial and ventral regions of the OB. In the Sema3A-deficient OB, NP-1-positive glomeruli spread over the entire OB, and we consistently found the ectopic arrangement of NP-1-positive glomeruli in the anteromedial and ventral regions. In addition, a specific subset of NP-1-negative and olfactory cell adhesion molecule-positive glomeruli, especially those in the anteromedial region, disappeared from the mutant OB. These results show a critical role for Sema3A in the spatial arrangement of glomeruli in the OB. Optical imaging from the dorsal OB showed that the distorted glomerular map conserved molecular-feature domains. However, the positions of the domains were shifted, which suggests a secondary rearrangement of the glomerular map in the Sema3A-deficient OB.

Animals↗

[Neurogliaform cells: neurochemistry, spatial arrangement, and their role in the neocortical inhibitory system].

The neurogliaform cells (NGFC) localized in area 4 of the human motor cortex were found to express choline acetyl transferase (ChAT), GABA, and calbindin. ChAT-positive neurons were located in cortical layer II. Their dendrites lay in a close proximity to those of pyramid cells, neighbouring neurogliaform cells, and bodies and dendrites of other cortical neurons. The NGFCs revealed by Golgi staining fell into two groups. Cells of the first group had locally (within cortical layer II) spreading axons, while those of the second group had axons extending into the adjacent layers. Neurochemical heterogeneity of NGFCs is discussed in the context of information processing in cortical modules and interaction of excitatory and inhibitory interneurons.

Adult↗

High spatial resolution readout of 3-D metabolic organ structure: an automated, low-temperature redox ratio-scanning instrument.

Intraorgan compartmentation of metabolic processes plays an important role in the understanding of the physiological function of the integrated organ under normal as well as under pathological conditions. We describe here a technique by which 3-D information on tissue redox state may be obtained by means of automated scanning of surface fluorescence. The instrument allows for serial scanning of frozen tissue. A typical scan of a tissue volume of 3 X 3 X 2 mm at a linear resolution of 50 micron and a spatial resolution of ca. 3 X 10(-7) ml includes 144,000 single-point measurements of pyridine nucleotide and flavoprotein fluorescence within the tissue block. The scanning process is fully computerized and programs have been developed which allow 2- or 3-D reconstruction of the data in terms of "redox ratio models," exemplified here by a 3-D model of a spreading depression wave in the cerebral cortex of a gerbil.

Animals↗

Monitoring the temporal and spatial activation pattern of astrocytes in focal cerebral ischemia using in situ hybridization to GFAP mRNA: comparison with sgp-2 and hsp70 mRNA and the effect of glutamate receptor antagonists.

We investigated the temporo-spatial expression of astrocyte glial fibrillary acidic protein (gfap) and sulfated glycoprotein 2 (sgp-2) mRNAs in comparison to 70-kDa heat shock protein (hsp70) mRNA by in situ hybridisation in rats subjected to permanent occlusion of the middle cerebral artery (MCA). Gfap mRNA started to increase in the cingulate cortex of the lesioned hemisphere 6 h after MCA occlusion and gradually spread over the lateral part of the ipsilateral cortex and the striatum from 12 h to 3 days, peaking at 3 days after MCA occlusion. Gfap mRNA also increased in the contralateral cingulate cortex and corpus callosum at 12 and 24 h. Hsp70 mRNA increased markedly in the ipsilateral cortex adjacent to the ischemic lesion, and slightly within the lesion area from 3 to 24 h and disappeared after 3 days. By 7 days, gfap and sgp-2 mRNAs were increased markedly in the peri-infarct area, and in the ipsilateral thalamus parallel with the delayed neuronal damage, whereas the widespread increase of gfap mRNA in the ipsilateral hemisphere declined. Post-occlusion treatment with the glutamate receptor antagonists MK-801 and NBQX slightly attenuate the induction of gfap but did not qualitatively affect the topical expression pattern. Within the cingulate cortex MK-801 treatment resulted in a significant decrease of the signal intensity at all survival times, reflecting most likely an attenuation of lesion-induced spreading depression like depolarization waves by MK-801. The area of hsp70 expression was reduced by both MK-801 and NBQX, most likely reflecting the decrease of the lesion area by both treatment regimens. Our study thus revealed an early and widespread increase of gfap mRNA in the non-ischemic area including the contralateral hemisphere starting between 3 and 6 h, and a delayed circumscribed expression in the peri-infarct border zone after 1 week. Comparison with the expression of hsp70 mRNA suggests that the absence of an early gfap mRNA induction in the peri-lesion zone reflects an impairment of astrocytic function which may be of importance for infarct growth during the early evolution of the pathological process.

Animals↗

Fundus autofluorescence imaging in Best's vitelliform dystrophy.

BACKGROUND: It is well known that with age lipofuscin accumulates in the retinal pigment epithelium (RPE). In many inherited macular dystrophies such as Best's disease abnormally high levels of lipofuscin were found by histopathological studies. In recent years, it has become possible to detect and image fundus autofluorescence in the living eye as an index of lipofuscin accumulation in the RPE. The aim of our study was to document the intrinsic fundus autofluorescence in patients with different stages of Best's disease and to correlate fundoscopic features with visual function in these patients. METHODS: Images of fundus autofluorescence were obtained from 10 patients with Best's vitelliform dystrophy, using a Heidelberg Retina Angiograph (HRA). Argon laser light (488 nm) was used for illumination, and a wide-bandpass filter with a cutoff of 500 nm was inserted in front of the detector to obtain the autofluorescence images. Images were compared with fundus appearance and fluorescein angiograms as well as with visual acuity, colour vision, visual fields and electrophysiological recordings in these patients. RESULTS: In initial stages of Best's disease, there were localised areas of hyperfluorescence centrally in the fovea, later being replaced by central hypofluorescence (atrophic) areas surrounded by hyperfluorescent rings. The evolution of autofluorescence pattern showed centrifugal spreading of retinal dysfunction from the centre towards periphery. Atrophic regions of the RPE were associated with low levels of background autofluorescence, lower visual acuity, abnormal colour vision (70% of patients), central scotomas (85% of patients) and poorer electrophysiological results (reduced PERG responses in 45% of patients with Best's disease). CONCLUSIONS: Fundus autofluorescence imaging provides new information regarding the content and spatial distribution of RPE lipofuscin in eyes with Best's disease, which appears to correspond to retinal function. This may "in vivo" give important clues to the pathogenesis and progression of Best's disease in which non-invasive autofluorescence imaging may replace fluorescein angiography.

Adolescent↗

Critical properties of lattices of diffusively coupled quadratic maps.

We study the critical properties of lattices of coupled logistic maps in the regime where the individual maps are closely above the onset of chaos. We discuss both spatial and temporal characteristics and especially the link between them. We show that the mutual information function between two points on the lattice decays exponentially with distance. In this way we find support for the relation xi approximately lambda(-1/2) between the coherence length xi and the largest Lyapunov exponent lambda which is further corroborated by a detailed study of the spreading of small perturbations. Finally we study the structure function of the lattice field variable. It shows that at the onset of chaos the lattice remains smooth.

Journal Article↗

Position of nuclear medicine modalities in the diagnostic work-up of breast cancer.

Breast tumors can be imaged by different modalities: mammography is the most widely used technique because of its diagnostic value, patient compliance and low costs. Some techniques such as ultrasound (US) are often indicated, while others, such as digital mammography and magnetic resonance imaging (MRI) are still under evaluation and seem to be very promising. Among the nuclear medicine techniques breast scintigraphy with (99m)Tc-labelled lipophilic cations (SestaMIBI or tetrofosmin), positron emission tomography (PET) with 18F-2-deoxy-2-fluoro-D-glucose (FDG) have been evaluated in many clinical trials. At present breast scintigraphy has limited applications due to its poor spatial resolution, which has a minimum of 8 mm. It is questionable whether single photon emission tomography (SPECT) can offer any substantially better information on the breast; however, SPECT is more accurate in detecting axillary lymph nodes. Recent approaches using breast dedicated collimators and cameras have greatly improved the SPECT resolution and sensitivity. The most interesting technique offered by nuclear medicine today are PET and lymphoscintigraphy with the intraoperative detection of handled gamma probe. The sentinel node detection has achieved a large consensus of reliability and at present it has an important place in the clinical management. In the same time many authors have acknowledged the value of PET in the differential diagnosis of breast lesions and in locoregional staging, since breast cancer is strongly avid for glucose. PET demonstrated also its efficacy in detecting axillary lymph node metastases. Even in some clinical trials its accuracy proved nearly comparable to that of lymphoscintigraphy with sentinel node biopsy, other studies showed that PET scanning does not currently have adequate spatial resolution to detect both micro- and small macrometastatic disease in axillary lymph nodes. The added value of PET in breast cancer staging is that with a single examination PET allows the characterisation of breast lesions, in addition to complete viewing of the entire body. Whole-body PET may substitute other diagnostic assessments by examining the various regions of potential tumour spread. The current diagnostic work-up for pre- and postoperative staging includes various examinations: chest X-rays, US of the abdomen, mammography of the contralateral breast. Bone scintigraphy with (99m)Tc-diphosphonates and laboratory tests can also be considered in women with large tumors or in symptomatic patients. Computed tomography (CT) and MRI may be used in order to resolve particular diagnostic problems. The current application of some of these modalities depends on the risk of the single patient of developing metastatic spread, which is revealed by a number of prognostic parameters of tumor aggressiveness and of course, clinical stage. Bone scintigraphy and PET may be useful in monitoring therapy response and in detecting tumour relapses during follow-up. In particular PET guided by tumor markers measurements shows to detect more lesions than other non nuclear medicine modalities.

Bone Neoplasms↗

[Diagnostic and prognostic significance of the changes in vectorcardiographic QRS and T waves in ischemic heart disease].

In various clinical forms of coronary disease, vectorcardiographic changes are mostly dependent on the depth and spread of necrotic and dystrophic myocardial changes. In ischemia, T wave only changes its trend, while in small-focus dystrophies and necrosis, it changes both in terms of trend and shape, and in limited myocardial infraction, changes in T shape and trend are combined with those of QRS complex. The more profound and expanded the necrotic changes, the more pronounced are spatial, phasic and morphological changes in QRS and T waves, while the ratio of T and QRS are-as (AT/AQRS) exceeds 60%. Vectorcardiograms showing simultaneous morphological, phasic and spatial changes in QRS and T waves, with DI (dynamic index of electrical activity) exceeding 60% in records from 2 and more leads, indicate marked necrotic myocardial changes and poor prognosis for the outcome of acute myocardial infarction.

Coronary Disease↗

Spatial and temporal accumulation of mRNAs encoding two common lignin peroxidases in Phanerochaete chrysosporium.

Accumulation of peroxidases and their mRNAs was localized in colonies of Phanerochaete chrysosporium sandwiched between perforated polycarbonate membranes. Northern (RNA) blot analyses of colonial rings and in situ hybridizations with specific probes for manganese(II)-dependent peroxidase (MnP-1) and lignin peroxidase (LiP H8) mRNAs indicated that the expression of MnP-1 and Lip H8 genes started simultaneously in the central area of 3-day-old colonies. With time the signals for both transcripts spread to more-peripheral areas while decreasing in intensity. Furthermore, the appearance of MnP protein, as detected with specific immune serum, immediately followed accumulation of the MnP-1 mRNA transcript. However, LiP protein could be detected only some time after accumulation of LiP H8 mRNA.

Cell Compartmentation↗

Spatial relation of the acetylcholinesterase-rich domain to the visual topography in the feline superior colliculus.

The superior colliculus (SC) of the cat shows a prominent compartmentalized organization at the level of its intermediate layers. The mosaic of these compartments is apparent in the pattern of acetylcholinesterase (AChE) staining. Patches of high AChE-activity are sharply set off from surrounding areas in the caudal SC while they are less distinct anteriorly. The rostral part lacks such obvious compartments. Thus, a structural reorganization apparently cuts across the topographical representations spread out in the SC. In order to test if this compartmental gradient relates to the topographic maps of the colliculus, retinotopic landmarks were visualized in the superficial layers by labeling the retinotectal pathway. In the SC ipsilateral to the eye injected with horseradish peroxidase (HRP) a paucity of labeling indicated the zone representing the ipsilateral visual half-field. Serial reconstructions of collicular sections, cut longitudinally or tangentially, revealed that the non-compartmentalized part of the intermediate layers corresponds to the representation of the ipsilateral visual half-field in the layers above, while an intricate mosaic array of compartments prevail in tectal zones related to the representation of the contralateral visual half-field.

Acetylcholinesterase↗

Thalamocortical inputs trigger a propagating envelope of gamma-band activity in auditory cortex in vitro.

To investigate how auditory cortex responds to thalamic inputs, we have used electrophysiological and anatomical techniques to characterize a brain slice containing functionally linked thalamocortical and intracortical pathways. In extracellular recordings, stimulation of thalamic afferents elicited a short-latency field potential and current sink in layer IV of the cortex, followed by 100-500 ms of polysynaptic activity containing rapid (gamma-band, 20-80 Hz) fluctuations. Paired intracellular and extracellular recordings showed that a short-latency excitatory postsynaptic potential (EPSP) corresponded to the fast extracellular potential, and that a slow intracellular depolarization with superimposed rapid fluctuations corresponded to the polysynaptic extracellular activity. Pharmacological manipulations demonstrated that glutamate receptors contributed to mono- and polysynaptic activity, and that the gamma-band fluctuations contained intermixed rapid depolarizations and Cl(-)-mediated inhibition. The spread of evoked activity through auditory cortex was determined by extracellular mapping away from the excitatory focus (the site of the largest amplitude fast response). The short-latency potential traversed auditory cortex at 1.25 m/s and decreased over 1-2 mm, likely reflecting sequential activation of cells contacted by thalamocortical arbors. In contrast, polysynaptic activity did not decrease but propagated as a spatially restricted wave at a 57-fold slower velocity (0.022 m/s). Thus, stimulation of the auditory thalamocortical pathway in vitro elicited a fast glutamatergic potential in layer IV, followed by polysynaptic activity, including gamma-band fluctuations, that propagated through the cortex. Propagating activity may form transient neural assemblies that contribute to auditory information processing.

2-Amino-5-phosphonovalerate↗

Genes expressed during imaginal discs morphogenesis: IMP-L2, a gene expressed during imaginal disc and imaginal histoblast morphogenesis.

We describe our analysis of IMP-L2, one of a set of six ecdysone-inducible genes in imaginal discs of Drosophila whose transcripts are associated with membrane-bound polysomes. The spatial and temporal patterns of expression of the IMP-L2 transcript were analyzed. This transcript is first expressed in imaginal discs in areas that are precursors of head and thoracic epithelium, particularly the peripodial epithelia. It is later expressed in the imaginal histoblasts, precursors of the adult abdomen. The appearance of IMP-L2 transcript in each of these tissues precedes the spreading and fusion of the separate imaginal anlagen to form the continuous adult epidermis.

Animals↗

Sensory uncertainty governs the extent of audio-visual interaction.

Auditory signals have been shown to exert a marked influence on visual perception in a wide range of tasks. However, the mechanisms of these interactions are, at present, poorly understood. Here we present a series of experiments where a temporal cue within the auditory domain can significantly affect the localisation of a moving visual target. To investigate the mechanism of this interaction, we first modulated the spatial positional uncertainty of the visual target by varying its size. When visual positional uncertainty was low (small target size), auditory signals had little or no influence on perceived visual location. However, with increasing visual uncertainty (larger target sizes), auditory signals exerted a significantly greater influence on perceived visual location. We then altered the temporal profile of the auditory signal by modulating the spread of its Gaussian temporal envelope. Introducing this temporal uncertainty to the auditory signal greatly reduced its effect on visual localisation judgements. These findings support the view that the relative uncertainty in individual sensory domains governs the perceptual outcome of multisensory integration.

Acoustic Stimulation↗

Molecular orbital studies on the mechanism of drug-receptor interaction. 2. beta-Adrenergic drugs. An approach to explain the role of the aromatic moiety.

The role of the aromatic moiety of beta-adrenergic drugs in the interaction with the receptor was investigated using the quantum mechanical ab initio SCF-MO-LCAO method. The structure-activity relationship was essentially discussed by analyzing the electrostatic molecular potential of three compounds which constitute meaningful portions of isoproterenol, INPEA, and doberol, the first drug having a stimulating activity and the others a blocking one. The results obtained point out the different roles played in the drug-receptor interaction by the various regions of the drugs and they also show that the aromatic moiety influences both the affinity and the intrinsic activity of the drugs. Indeed, the spatial correspondence among zones with negative potentials, which are localized on the phenyl substitutents of isoproterenol and INPEA and on the phenyl ring of doberol, could contribute to the affinity. On the other hand, the intrinsic activity of isoproterenol might be associated both with the proton-donor tendency of one phenolic OH group and with the wide zone of negative potential which spreads on a large part of the aromati moiety.

Ethanolamines↗

The geographical spread of influenza.

How infectious diseases spread in space within one cycle of an epidemic is an important question that has received considerable theoretical attention. There are, however, few empirical studies to support theoretical approaches, because data are scarce. Weekly reports obtained since 1984 from a network of general practitioners spanning the entire French territory allows the analysis of the spatio-temporal dynamics of influenza over a fine spatial scale. This analysis indicates that diffusion over long distances, possibly due to global transportation systems, is so quick that homogeneous global mixing occurs before the epidemic builds up within infected patches. A simple model in which the total number of cases is given by the empirical time-series and cases are randomly assigned to patches according to the population weight of the patches exhibits the same spatio-temporal properties as real epidemic cycles: homogeneous mixing models constitute appropriate descriptions, except in the vicinity of the epidemic's peak, where geographic heterogeneities play a role.

Epidemiologic Studies↗