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Reconstruction of cardiac ventricular geometry and fiber orientation using magnetic resonance imaging.

An imaging method for the rapid reconstruction of fiber orientation throughout the cardiac ventricles is described. In this method, gradient-recalled acquisition in the steady-state (GRASS) imaging is used to measure ventricular geometry in formaldehyde-fixed hearts at high spatial resolution. Diffusion-tensor magnetic resonance imaging (DTMRI) is then used to estimate fiber orientation as the principle eigenvector of the diffusion tensor measured at each image voxel in these same hearts. DTMRI-based estimates of fiber orientation in formaldehyde-fixed tissue are shown to agree closely with those measured using histological techniques, and evidence is presented suggesting that diffusion tensor tertiary eigenvectors may specify the orientation of ventricular laminar sheets. Using a semiautomated software tool called HEARTWORKS, a set of smooth contours approximating the epicardial and endocardial boundaries in each GRASS short-axis section are estimated. These contours are then interconnected to form a volumetric model of the cardiac ventricles. DTMRI-based estimates of fiber orientation are interpolated into these volumetric models, yielding reconstructions of cardiac ventricular fiber orientation based on at least an order of magnitude more sampling points than can be obtained using manual reconstruction methods.

Animals↗

Patella lead x-ray fluorescence measurements are independent of sample orientation.

In vivo x-ray fluorescence bone lead measurements assess long-term lead exposure. Tibia, calcaneus, and patella are the most commonly sampled bones. Patella measurements also include lead signals from the distal femur, proximal tibia, and synovium. It is therefore important to know whether the orientation of the patella relative to the measurement system substantially affects the measured patella lead concentrations and their measurement uncertainties. This study examined whether these parameters exhibited a dependence on the orientation of the patella with respect to the measurement system, a dependence that could arise from varying nonpatella contributions. There was no effect of orientation on measured patella lead concentration, but there was a highly significant effect of orientation on the measurement uncertainty. These data do not conclusively show that there are no nonpatella contributions to a patella lead measurement; rather, that any such contributions are not a function of measurement orientation over the range of orientations considered. Further study is required if the contribution of nonpatella tissues to a patella lead XRF-measured concentration is to be fully addressed. This study also filled a gap in the literature by quantifying the within-patella (29%) and between-patella (71%) variability of measured patella lead concentrations from replicate measures of nine patellae.

Adult↗

Beam orientation optimization for IMRT by a hybrid method of the genetic algorithm and the simulated dynamics.

We have developed a new method for beam orientation optimization in intensity-modulated radiation therapy (IMRT). The problem of beam orientation optimization in IMRT is solved by a decoupled two-step iterative process: (1) optimization of the intensity profiles for given beam configurations; (2) selection of optimal beam configurations based on the ranking by an objective function score for the results of the intensity profile optimization. The simulated dynamics algorithm is used for the intensity profile optimization. This algorithm enforces both the hard constraints and dose-volume constraints. A genetic algorithm is used to select beam orientation configurations. The method has been tested for both a simulated and clinical case, and the results show that beam orientation optimization significantly improved IMRT plans within a time period that is clinically acceptable. The results also show the dependence of the optimal orientation configurations on the prescribed constraints. In addition, beam orientation optimization by the method described here can provide multiple plans with similar dose distributions. This degeneracy characteristic can be exploited to our advantage in introducing additional planning objectives, e.g., the smoothness of intensity profiles, for the selection of the optimal plan among the degenerate configurations for treatment delivery.

Algorithms↗

Orientation dependence of trinucleotide CAG repeat instability in Saccharomyces cerevisiae.

To examine the chromosomal stability of repetitions of the trinucleotide CAG, we have cloned CAG repeat tracts onto the 3' end of the Saccharomyces cerevisiae ADE2 gene and placed the appended gene into the ARO2 locus of chromosome VII. Examination of chromosomal DNA from sibling colonies arising from clonal expansion of strains harboring repeat tracts showed that repeat tracts often change in length. Most changes in tract length are decreases, but rare increases also occur. Longer tracts are more unstable than smaller tracts. The most unstable tracts, of 80 to 90 repeats, undergo changes at rates as high as 3 x 10(-2) changes per cell per generation. To examine whether repeat orientation or adjacent sequences alter repeat stability, we constructed strains with repeat tracts in both orientations, either with or without sequences 5' to ADE2 harboring an autonomously replicating sequence (ARS; replication origin). When CAG is in the ADE2 coding strand of strains harboring the ARS, the repeat tract is relatively stable regardless of the orientation of ADE2. When CTG is in the ADE2 coding strand of strains harboring the ARS, the repeat tract is relatively unstable regardless of the orientation of ADE2. Removal of the ARS as well as other sequences adjacent to the 5' end of ADE2 alters the orientation dependence such that stability now depends on the orientation of ADE2 in the chromosome. These results suggest that the proximity of an ARS or another sequence has a profound effect on repeat stability.

DNA, Fungal↗

Gaze control in the cat: studies and modeling of the coupling between orienting eye and head movements in different behavioral tasks.

1. Orienting movements, consisting of coordinated eye and head displacements, direct the visual axis to the source of a sensory stimulus. A recent hypothesis suggests that the CNS may control gaze position (gaze = eye-relative-to-space = eye-relative-to-head + head-relative-to-space) by the use of a feedback circuit wherein an internally derived representation of gaze motor error drives both eye and head premotor circuits. In this paper we examine the effect of behavioral task on the individual and summed trajectories of horizontal eye- and head-orienting movements to gain more insight into how the eyes and head are coupled and controlled in different behavioral situations. 2. Cats whose heads were either restrained (head-fixed) or unrestrained (head-free) were trained to make orienting movements of any desired amplitude in a simple cat-and-mouse game we call the barrier paradigm. A rectangular opaque barrier was placed in front of the hungry animal who either oriented to a food target that was visible to one side of the barrier or oriented to a location on an edge of the barrier where it predicted the target would reappear from behind the barrier. 3. The dynamics (e.g., maximum velocity) and duration of eye- and head-orienting movements were affected by the task. Saccadic eye movements (head-fixed) elicited by the visible target attained greater velocity and had shorter durations than comparable amplitude saccades directed toward the predicted target. A similar observation has been made in human and monkey. In addition, when the head was unrestrained both the eye and head movements (and therefore gaze movements) were faster and shorter in the visible- compared with the predicted-target conditions. Nevertheless, the relative contributions of the eye and head to the overall gaze displacement remained task independent: i.e., the distance traveled by the eye and head movements was determined by the size of the gaze shift only. This relationship was maintained because the velocities of the eye and head movements covaried in the different behavioral situations. Gaze-velocity profiles also had characteristic shapes that were dependent on task. In the predicted-target condition these profiles tended to have flattened peaks, whereas when the target was visible the peaks were sharper. 4. Presentation of a visual cue (e.g., reappearance of food target) immediately before (less than 50 ms) the onset of a gaze shift to a predicted target triggered a midflight increase in first the eye- and, after approximately 20 ms, the head-movement velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Raised object on a planar surface stroked across the fingerpad: responses of cutaneous mechanoreceptors to shape and orientation.

The representations of orientation and shape were studied in the responses of cutaneous mechanoreceptors to an isolated, raised object on a planar surface stroked across the fingerpad. The objects were the top portions of a sphere with a 5-mm radius, and two toroids each with a radius of 5 mm along one axis and differing radii of 1 or 3 mm along the orthogonal axis. The velocity and direction of stroking were fixed while the orientation of the object in the horizontal plane was varied. Each object was stroked along a series of laterally shifted, parallel, linear trajectories over the receptive fields of slowly adapting, type I (SA), and rapidly adapting, type I (RA) mechanoreceptive afferents innervating the fingerpad of the monkey. "Spatial event plots" (SEPs) of the occurrence of action potentials, as a function of the location of each object on the receptive field, were interpreted as the responses of a spatially distributed population of fibers. That portion of the plot evoked by the curved object (the SEPc) provided a representation of the shape and orientation of the two-dimensional outline of the object in the horizontal plane in contact with the skin. For both SAs and RAs, the major vector of the SEPc, obtained by a principal components analysis, was linearly related to the physical orientation of the major axis of each toroid. The spatial distribution of discharge rates [spatial rate surface profiles (SRSs), after plotting mean instantaneous frequency versus spatial locus within the SEPc] represented object shape in a third dimension, normal to the skin surface. The shape of the SA SRSs, well fitted by Gaussian equations, better represented object shape than that of the RA SRSs. A cross-sectional profile along the minor axis [spatial rate profile (SRP)] was approximately triangular for SAs. After normalization for differences in peak height, the falling slopes of the SA SRPs increased, and the base widths decreased with curvature of the object's minor axis. These curvature-related differences in slopes and widths were invariant with changes in object orientation. It is hypothesized that circularity in object shape is coded by the constancy of slopes of SA SRPs between peak and base and that the constancy of differences in the widths and falling slopes evoked by different raised objects encodes, respectively, the differences in their sizes and shapes regardless of differences in their orientation on the skin.

Action Potentials↗

Contrast-dependent nonlinearities arise locally in a model of contrast-invariant orientation tuning.

We study a recently proposed "correlation-based," push-pull model of the circuitry of layer 4 of cat visual cortex. This model was previously shown to explain the contrast-invariance of cortical orientation tuning. Here we show that it can simultaneously account for several contrast-dependent (c-d) "nonlinearities" in cortical responses. These include an advance with increasing contrast in the temporal phase of response to a sinusoidally modulated stimulus; a change in shape of the temporal frequency tuning curve, so that higher temporal frequencies may give little or no response at low contrast but reasonable responses at high contrast; and contrast saturation that occurs at lower contrasts in cortex than in the lateral geniculate nucleus (LGN). In the context of the model circuit, these properties arise from a mixture of nonlinear cellular and synaptic mechanisms: short-term synaptic depression, spike-rate adaptation, contrast-induced changes in cellular conductance, and the nonzero spike threshold. The former three mechanisms are sufficient to explain the experimentally observed increase in c-d phase advance in cortex relative to LGN. The c-d changes in temporal frequency tuning arise as a threshold effect: voltage modulations in response to higher-frequency inputs are only slightly above threshold at lower contrast, but become robustly suprathreshold at higher contrast. The other three nonlinear mechanisms also play a crucial role in this result, allowing contrast dependence of temporal frequency tuning to coexist with contrast-invariance of orientation tuning. Contrast saturation, and the observation that responses to stimuli of increasing temporal frequency saturate at increasingly high contrasts, can be induced both by the model's push-pull inhibition and by synaptic depression. Previous proposals explained these nonlinear response properties by assuming contrast-invariant orientation tuning as a starting point, and adding normalization by shunting inhibition derived equally from cells of all preferred orientations. The present proposal simultaneously explains both contrast-invariant orientation tuning and these contrast-dependent nonlinearities and requires only processing that is local in orientation, in agreement with intracellular measurements.

Animals↗

Survey of current practices in fellowship orientation.

BACKGROUND: The transition from medical resident to subspecialty fellow is a critical time period in fellowship training that has not been well described. The current practices of fellow orientation in pulmonary and critical care training programs are not known. OBJECTIVES: The aim of this study was to describe orientation practices for training programs in the United States. METHODS: A 10-question survey was sent via e-mail to program directors of pulmonary/critical care fellowship programs identified on the American Thoracic Society (ATS) web-page of current programs. RESULTS: Eighty-seven programs responded (61.7%), of which 86% had a formal orientation program. The mean time spent in fellow orientation was 5-10 h in didactic sessions and 0-5 h in wet labs. The most frequent didactic sessions were bronchoscopy in 69 programs (80.2%), pulmonary function testing in 63 programs (73.3%) and orientation to hospital services in 63 programs (73.3%). The most frequent use of wet labs was in bronchoscopy training in 60 programs (81.1%) and ventilators in 45 programs (60.8%). Simulators were used in 37 programs (43%). The majority reported that these areas were covered with on the job training, without a formal designated orientation. CONCLUSION: This survey demonstrated that early fellow training differs across programs in both time spent and clinical and procedural topics covered. An early, standardized approach to clinical and procedural training can assure appropriate exposure that cannot be guaranteed by on the job training. To provide justification for such an approach, clinical outcomes need to be correlated with training methods.

Bronchoscopy↗

Teaching problem-oriented therapy.

The therapeutic concept is problem- and patient-oriented. In analogy to it the didactic concept is problem- and therapist-oriented. The essential point is learning in groups from practical cases. Problem-oriented in this context means that the problems-solving process in which the patient and the therapist are engaged is supported by the observer group. Therapist-oriented means that the learning process should take account of the different preferences and experiences of the therapists. That can only be accomplished by problem-oriented learning. Each psychotherapy training group consists of 4 assistant doctors and a supervisor and stays together about 1 year. The strongly structured concept of problem-oriented therapy (POT) [Blaser et al., 1988] offers the beginner a framework by which he can guide the dialogue with the patient. The eclecticism of POT allows the more experienced therapist to try out new methods without losing track of the problem. The constantly changing role of being observer or therapist supports the group coherence, and furthermore it promotes an important element of therapeutic competence, the ability to get into a close relation with the patient and at the same time being able to observe oneself, the patient and the therapeutic process from a more distant view. In addition to the POT training group tutorials in special psychotherapy methods and single supervision sessions are offered.

Clinical Competence↗

Dynamically oriented psychotherapy with borderline patients.

This article outlines a basic framework and strategy for a dynamically oriented psychotherapy with borderline patients. Focus includes arrangements and guidelines for psychotherapy, neutrality, the stability of the therapeutic environment, the therapeutic alliance, transference, the countertransference, activity of the therapist, types of interventions, style of interventions, interventions regarding core difficulties, the conceptual framework of anxiety and defense, trends in the psychotherapy, and termination. A differentiation between analytically oriented psychotherapy and dynamically oriented psychotherapy is provided. For one group of borderline patients, a modified analytically oriented approach is utilized throughout the entire treatment. For a second group, there is a switch from analytically oriented psychotherapy to a dynamically oriented psychotherapy, after the therapeutic alliance has become reasonably stable. Two clinical vignettes are provided.

Acting Out↗

Jaw muscle orientation and moment arms of long-face and normal adults.

Long-face subjects have strongly reduced bite forces relative to normal subjects. This difference cannot be fully explained by the reduced cross-sectional area of the jaw muscles. In this study, we investigated whether the orientation and moment arms of the jaw muscles of normal and long-face subjects are different, and if so, to what extent these differences contribute to the observed differences in maximum molar bite-force levels. Three MRI scan series with different orientations were made of the jaw muscles of 30 normal and 13 long-face subjects. These served as the basis for computer reconstructions of the external shape of the muscles. The spatial orientation of the jaw muscles was defined by the regression line through the centroids of the muscular cross-sections. The moment arms of the jaw muscles and the bite point of the first mandibular molar were measured with respect to the center of the ipsilateral condyle. The muscular variables-including angles, moment arms, and mechanical advantage-were analyzed with a discriminant analysis and a multivariate analysis of variance (MANOVA). Differences in the spatial orientation of the temporalis muscle and the anterior digastric muscle contributed most to the distinction of the normal and long-face group. With MANOVA, it was shown that the normal and long-face group did not significantly differ with respect to the jaw muscle moment arms and mechanical advantage data. Only small differences were found between the sagittal muscle angles of the masseter and anterior digastric muscles in the two groups. In both the normal and long-face group, the orientation and moment arm data of the right and left muscles differed significantly. It was concluded that the variation of the spatial orientation of the jaw muscles is small and does not significantly contribute to the explanation of the different molar bite-force levels of long-face and normal subjects. Therefore, it is tempting to assume that the jaw muscles of normal and long-face subjects are different with respect to the maximum force they can exert per unit of cross-sectional area.

Adult↗

The incidence and nature of letter orientation errors in reading disability.

Letter orientation confusions (reversals) in the reading and writing of 10-year-old children with and without reading disability were investigated to determine whether reading disability is associated with letter orientation errors and to identify the nature of the errors. In a variety of tasks measuring letter orientation confusions in reception (reversal detection and recognition) and production (controlled writing, copying), individuals with reading disability made more orientation confusions than average readers. Orientation errors were more frequent for reversible than for nonreversible items in tasks involving long-term memory processes. The results did not appear to be related to group differences in attention or speed of motor responding. Possible sources of orientation confusions, including deficient magnocellular system processing, mislabeling, and overreliance on visual strategies, are discussed.

Case-Control Studies↗

Implicit and explicit measures of sexual orientation attitudes: in group preferences and related behaviors and beliefs among gay and straight men.

The relations among implicit and explicit measures of sexual orientation attitudes and sexual-orientation-related behavior and beliefs among gay men (Study 1) and straight men (Studies 1 and 2) were explored. Study 1 found relations between implicit and explicit measures of sexual orientation attitudes, large differences between gay and straight men on both implicit and explicit measures, and that these measures predicted sexual-orientation-related behaviors among gay men. Also, only straight men exhibited a negative relation between their attitudes toward homosexuality and heterosexuality. Study 2 found that as straight men held more negative attitudes toward homosexuality, they more strongly endorsed the importance of heterosexual identity and of traditional masculine gender roles. These endorsements mediated the negative relation between their attitudes toward heterosexuality and homosexuality. Implications for assessing attitudes toward sexual orientation and their relations for sexual orientation identity are discussed.

Attitude↗

Tensile properties of the human femur-anterior cruciate ligament-tibia complex. The effects of specimen age and orientation.

The structural properties of 27 pairs of human cadaver knees were evaluated. Specimens were equally divided into three groups of nine pairs each based on age: younger (22 to 35 years), middle (40 to 50 years), and older (60 to 97 years). Anterior-posterior displacement tests with the intact knee at 30 degrees and 90 degrees of flexion revealed a significant effect of knee flexion angle, but not of specimen age. Tensile tests of the femur-ACL-tibia complex were performed at 30 degrees of knee flexion with the ACL aligned vertically along the direction of applied tensile load. One knee from each pair was oriented anatomically (anatomical orientation), and the contralateral knee was oriented with the tibia aligned vertically (tibial orientation). Structural properties of the femur-ACL-tibia complex, as represented by the linear stiffness, ultimate load, and energy absorbed, were found to decrease significantly with specimen age and were also found to have higher values in specimens tested in the anatomical orientation. In the younger specimens, linear stiffness (242 +/- 28 N/mm) and ultimate load (2160 +/- 157 N) values found when the femur-ACL-tibia complex was tested in the anatomical orientation were higher than those reported previously in the literature. These values provide new baseline data for the design and selection of grafts for ACL replacement in an attempt to reproduce normal knee kinematics.

Age Factors↗

Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation.

New blood vessel formation requires the coordination of endothelial cell division and the morphogenetic movements of vessel expansion, but it is not known how this integration occurs. Here, we show that endothelial cells regulate division orientation during the earliest stages of blood vessel formation, in response to morphogenetic cues. In embryonic stem (ES) cell-derived vessels that do not experience flow, the plane of endothelial cytokinesis was oriented perpendicular to the vessel long axis. We also demonstrated regulated cleavage orientation in vivo, in flow-exposed forming retinal vessels. Daughter nuclei moved away from the cleavage plane after division, suggesting that regulation of endothelial division orientation effectively extends vessel length in these developing vascular beds. A gain-of-function mutation in VEGF signaling increased randomization of endothelial division orientation, and this effect was rescued by a transgene, indicating that regulation of division orientation is a novel mechanism whereby VEGF signaling affects vessel morphogenesis. Thus, our findings show that endothelial cell division and morphogenesis are integrated in developing vessels by flow-independent mechanisms that involve VEGF signaling, and this cross talk is likely to be critical to proper vessel morphogenesis.

Animals↗

Myelin contributes to the parallel orientation of axonal growth on white matter in vitro.

BACKGROUND: Brain and spinal cord white matter can support extensive axonal growth. This growth is generally constrained to an orientation that is parallel to the longitudinal axis of the fiber tract. This constraint is presumably due to permissive and non-permissive substrates that are interleaved with each other and oriented in parallel within the tract. RESULTS: Embryonic chick sympathetic neurons were cultured on cryostat sections of rat brain and the orientation of neurite growth on white matter was assessed. To determine if haptotaxis is sufficient to guide parallel neurite growth, neurons were cultured under conditions designed to interfere with interactions between growing neurites and factors that act as biochemical contact guidance cues but not interactions with haptotactic cues. Under these conditions, neurites extending on white matter were not exclusively oriented in parallel to the fiber tract, suggesting that biochemical cues are involved. To assess the role of myelin in guiding parallel neurite growth, neurons were cultured on myelin-deficient corpus callosum. These neurons also extended neurites that were not constrained to a parallel orientation. Moreover, preincubation with NGF and treatment with cAMP analogs, manipulations that attenuate overall myelin-mediated inhibition of neurite growth, also led to a reduced parallel orientation of neurite growth. CONCLUSIONS: The present studies suggest that some of the relevant factors that constrain axonal growth on white matter are not haptotactic in nature and appear to be partly mediated by factors that are associated with myelin and may involve myelin-associated "inhibitors".

Animals↗

A 90-degree rotation of the mitotic spindle changes the orientation of mitoses of zebrafish neuroepithelial cells.

In the neural plate and neural tube in the trunk region of the zebrafish embryo, dividing cells are oriented parallel to the plane of the neuroepithelium, while in neural keel/rod, cells divide perpendicular to it. This change in the orientation of mitosis is brought about by a 90 degrees rotation of the mitotic spindle. As the two halves of the neural primordium in keel/rod stage are in apposition, the perpendicular orientation of mitoses in this stage determines that daughter cells become allocated to both sides of the neural tube. To assess the role played by cell junctions in controlling the orientation of dividing cells, we studied the expression of components of adherens and tight junctions in the neuroepithelial cells. We find that these proteins are distributed irregularly at the neural plate stage and become polarised apically in the cell membrane only during the keel/rod stage. The stereotypic orientation of mitoses is perturbed only weakly upon loss of function of the cell junction components ASIP and aPKClambda, suggesting that mitotic orientation depends in part on the integrity of cell junctions and the polarity of the epithelium as a whole. However, the 90-degree rotation of the spindle does not require perfectly polarised cell junctions between the neuroepithelial cells.

Animals↗

The let-99 gene is required for proper spindle orientation during cleavage of the C. elegans embryo.

The orientation of cell division is a critical aspect of development. In 2-cell C. elegans embryos, the spindle in the posterior cell is aligned along the long axis of the embryo and contributes to the unequal partitioning of cytoplasm, while the spindle in the anterior cell is oriented transverse to the long axis. Differing spindle alignments arise from blastomere-specific rotations of the nuclear-centrosome complex at prophase. We have found that mutations in the maternally expressed gene let-99 affect spindle orientation in all cells during the first three cleavages. During these divisions, the nuclear-centrosome complex appears unstable in position. In addition, in almost half of the mutant embryos, there are reversals of the normal pattern of spindle orientations at second cleavage: the spindle of the anterior cell is aligned with the long axis of the embryo and nuclear rotation fails in the posterior cell causing the spindle to form transverse to the long axis. In most of the remaining embryos, spindles in both cells are transverse at second cleavage. The distributions of several asymmetrically localized proteins, including P granules and PAR-3, are normal in early let-99 embryos, but are perturbed by the abnormal cell division orientations at second cleavage. The accumulation of actin and actin capping protein, which marks the site involved in nuclear rotation in 2-cell wild-type embryos, is abnormal but is not reversed in let-99 mutant embryos. Based on these data, we conclude that let-99(+) is required for the proper orientation of spindles after the establishment of polarity, and we postulate that let-99(+) plays a role in interactions between the astral microtubules and the cortical cytoskeleton.

Actins↗