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Mitochondrial motility in axons: membranous organelles may interact with the force generating system through multiple surface binding sites.

In living tissue, membrane-bound organelles, including mitochondria, move along parallel cytoplasmic pathways. Motion is directed and tends to be confined to a single path. Deviations from this single path motion are rare. When present, however, they tend to occur at points of intersection of cytoskeletal linear elements (LE). Such intersections are relatively uncommon in intact axons and extruded axoplasm. However, we have found that such intersections can be produced in extruded preparations by shear forces directed tangential to the axoplasmic surface. We have studied the detailed behavior of mitochondria in extruded squid axoplasm. Special attention was directed to the relationship between mitochondrial shape changes and orientation of cytoskeletal LE. The most striking of these changes in shape is branching. In this process, the mitochondrion transiently assumes a triradial (three-ended) shape. This appearance may be maintained for seconds to minutes before the normal cylindrical shape is resumed by absorption of either the newly formed end or, more commonly, one of the original ends. The frequency of branching appears to be dependent on the degree of cytoskeletal organization. It becomes more common as the number of apparent intersections between cytoskeletal LE increases. Further, the formation of new ends seems to occur along paths defined by cytoskeletal elements. These observations suggest that the mitochondrial membrane is multivalent. That is, it contains multiple sites capable of interacting with the axonal force generation apparatus. Furthermore, LE in the cytoskeleton may indicate the paths along which these interactions are permissible.

Animals↗

A specific brain tract guides follower growth cones in two regions of the zebrafish brain.

Neurons of the nucleus of the posterior commissure (nuc PC), an identifiable cluster of neurons in the embryonic zebrafish brain, project growth cones ventrally along the posterior commissure to the anterior tegmentum where the PC intersects two longitudinal tracts, the tract of the postoptic commissure (TPOC) and the medial longitudinal fasciculus (MLF). Once at the intersection, nuc PC growth cones turn posteriorly onto the TPOC in the dorsal tegmentum and follow it to the hindbrain. Previously we showed that in the absence of the TPOC, nuc PC growth cones often extended along aberrant pathways suggesting that fasciculation, that is, contact with TPOC axons is an important factor in guiding growth cones along their normal pathway. However, a significant number of nuc PC growth cones also followed their normal pathway suggesting that cues associated with the dorsolateral tegmentum, independent of the TPOC, can also guide nuc PC growth cones. We have now confirmed using electron microscopy that nuc PC growth cones fasciculate with axons in the TPOC. In the absence of the TPOC, the nuc PC growth cones that extend along their normal pathway do so in contact with dorsolateral neuroepithelial cells. This suggests that cues associated with these cells can also guide the nuc PC growth cones. Furthermore, in the absence of the TPOC axons, these growth cones now inappropriately turn onto axons that normally intersect the TPOC near the border of the midbrain and hindbrain, that is, at a second intersection of tracts. This suggests that fasciculation with TPOC axons may also guide nuc PC growth cones in this second region of the brain.

Animals↗

Sonographic anatomy of the rectus sheath: an indication for new terminology and implications for rectus flaps.

With the aim of standardizing descriptions of lesions on the anterior abdominal wall and definition of reconstructive flaps, the sonographic anatomy of the rectus sheath has been studied in 8 subjects. Anatomic terms have been suggested for the various segments and intersections of the sheath. The linea abla, linea semilunaris, formation of rectus sheath, segments and intersections have been described and illustrated. Identical segments and intersections were found to have characteristic sonographic features in all subjects. The intersection below the umbilicus was observed in 1 out of 8. Ultrasound capability in the determination of size and extent of tissues is discussed. It is hoped that the use of the suggested terminology and the preoperative ultrasonic definition of rectus flaps, may provide basis for objective comparison of results of reconstructive surgery.

Humans↗

Collision judgment of objects approaching the head.

Recent investigations have indicated that human perception of the trajectory of objects approaching in the horizontal plane is precise but biased away from straight ahead. This is remarkable because it could mean that subjects perceive objects that approach on a collision course as missing the head. Approach within the horizontal plane through the eyes and the fixation point (the plane of regard) is special, as general motions will also have a component of motion perpendicular to the plane of regard. Thus, we investigated three-dimensional motion perception in the vicinity of the head, including vertical components. Subjects judged whether an object that moved in the mid-sagittal plane was going to hit below or above a well-known reference point on the face like the center of the chin or the forehead (perceptual task). Tactile and proprioceptive information about the reference point significantly improved precision. Precision did not change with distance of the approaching target or with fixation direction. Bias was virtually absent for these vertical motions. When subjects pointed with their index finger to the perceived location of impact on their face (visuo-motor task), they overestimated (1.7 cm) the horizontal eccentricity of the point of impact (pointing task). Vertical bias, however, was again virtually absent. Interestingly, when trajectories intersected the plane of regard, higher precision was observed in the perceptual task regardless of the other conditions. In contrast, neither bias nor precision of the pointing task changed significantly when the trajectories intersected the plane of regard. When asked to point to the location where a trajectory intersected the plane of regard, subjects overestimated the depth component of this intersection location by about 3 cm. The absence of perceptual and pointing bias in the vertical direction in contrast to the clear horizontal bias suggests that different (combinations of) cues are used to judge these components of the trajectory of an approaching object. The results of our perceptual task suggest a role for somatosensory signals in the visual judgment of impending impact.

Analysis of Variance↗

A simpler way of comparing the labelling densities of cellular compartments illustrated using data from VPARP and LAMP-1 immunogold labelling experiments.

Quantitative immunoelectron microscopy of gold label in intracellular compartments often involves calculating labelling densities (LDs). These are related to antigen concentrations and usually refer gold particle counts to the sizes of compartments on sections (for example, golds per microm(2) of organelle profile area or per microm of membrane trace length). Here, we show how LD values can be estimated more simply (without estimating areas or lengths) and also how observed and expected LD values can be used to calculate a relative labelling index (RLI) for each compartment and then test statistically for preferential (non-random) labelling. For random labelling, RLI=1. Compartment size is estimated stereologically by superimposing random test points (which hit organelle profiles in proportion to their area) or test lines (which intersect membrane traces in proportion to their length). By this means, the observed LD of a compartment (LD(obs)) can be expressed simply as golds per test point (organelles) or per intersection (membranes). Furthermore, the LD obtained by dividing total golds (on all compartments) by total points or intersections (on all compartments) is the value to be expected (LD(exp)) when compartments label randomly. For each compartment, RLI=LD(obs)/LD(exp). Statistical analysis is undertaken by comparing observed distributions of golds with predicted random distributions (calculated from point or intersection counts). A compartment is preferentially labelled if two criteria are met: (1) its RLI>1 (i.e. LD(obs) is greater than LD(exp)) and (2) its partial chi-squared value makes a substantial contribution to total chi-squared value. This approach provides a simple and efficient way of comparing LDs in different compartments. Its utility is illustrated using data from VPARP and LAMP-1 labelling experiments.

Animals↗

Pedestrian safety at traffic signals: a study carried out with the help of a traffic conflicts technique.

Most pedestrian accidents in built-up areas occur at intersections. Even after signalization the number of accidents involving pedestrians often remains high. After reviewing the published evidence, this paper describes how the Traffic Conflicts Techniques has been used to examine the risk to pedestrians at 120 intersections. The principal results indicate that signalization of a high-speed intersection (mean speed above 30 km/h in at least one arm) reduces pedestrian risk to approximately half. If mean speed in every arm is below 30 km/h signalization also reduces pedestrian risk, as long as most vehicles are not turning. Another finding from these studies was that a crosswalk should be located less than two meters from the intersection to optimize pedestrian safety. The conflict studies as well as analyses of accident data show that one should examine separately accidents between turning vehicles and "green-walking" pedestrians and accidents involving pedestrians walking against red light. The effect of an exclusive pedestrian signal phase (scramble) was tested at three sites and proved to be very safety-beneficial in a small town, while in Stockholm it did not prove effective because of a high percentage of red-walkers. Vehicle delay, as well as pedestrian delay, increased at all three sites. Data collected at 152 crosswalks has been used to estimate the parameters of a multivariate model of the frequency of "red-walking." The size of the town and traffic volumes appear to be the major factors influencing this frequency. Additional insight has been obtained from personal interviews of 450 persons. These indicate that shorter waiting times and police enforcement are considered the most efficient measures to reduce the frequency of red-walking.

Accident Prevention↗

Integral differences among human survival distributions as a function of disease.

The mortality kinetics of white humans of the United States were examined for 25 different age-related causes of death (22 male, 21 female). The survivorship distributions for these diseases clustered into groups, as defined by their position on the time axis. When the survivorship curves were linearized, by plotting as log(-log S(t] vs. log t, this clustering was easily identified as well-defined intersections among the lines separated by 2-year intervals. The four largest groups had intersections at approximate time values of 101, 99, 95, and 93 years, with a small group having an intersection at 97 years. The distribution of diseases among the intersections was not random but was related to sex and disease type. The two-parameter Weibull and GDCP (Gamma Distribution raised to a Combinatoric Power) functions were fit to the individual cause of death survivorship curves and yielded parametric values for the shape (slope) and median time to death. These two parameters varied with disease type and exhibited a positive, linear regression. The regression slope between the shape (alpha) and time (tau m) parameters of the GDCP was also equal to approximately 2 years. This suggested to us that the 2-year intervals in the median times of death with integral changes in the shape parameter and the 2-year time interval between the survivorship clusters may both arise from a similar process involving integral numbers of discrete steps.

Age Factors↗

Determining the potential safety benefit of improved lighting in three pedestrian crash scenarios.

The influence of light level was determined for three pedestrian crash scenarios associated with three adaptive headlighting solutions-curve lighting, motorway lighting, and cornering light. These results were coupled to corresponding prevalence data for each scenario to derive measures of annual lifesaving potential. For each scenario, the risk associated with light level was determined using daylight saving time (DST) transitions to produce a dark/light interval risk ratio; prevalence was determined using the corresponding annual crash rate in darkness for each scenario. For curve lighting, pedestrian crashes on curved roadways were examined; for motorway lighting, crashes associated with high speed roadways were examined; and for cornering light, crashes involving turning vehicles at intersections were examined. In the curve analysis, lower dark/light crash ratios were observed for curved sections of roadway compared to straight roads. In the motorway analysis, posted speed limit was the dominant predictor of this ratio for the fatal crash dataset; road function class was the dominant predictor of the ratio for the fatal/nonfatal dataset. Finally, in the intersection crash analysis, the dark/light ratio for turning vehicles was lower than for nonturning vehicles; and the ratio at intersections was lower than at non-intersections. Relative safety need was determined by combining the dark/light ratio with prevalence data to produce an idealized measure of lifesaving potential. While all three scenarios suggested a potential for safety improvement, scenarios related to high speed roadway environments showed the greatest potential.

Accidents, Traffic↗

Accuracy of serial transverse cross-sections in detecting residual basal cell carcinoma at the surgical margins of an elliptical excision specimen.

BACKGROUND: There has been no published study estimating the proportion of positive surgical margins that is missed when serial transverse cross-sectioning (bread-loafing) is used to histologically evaluate the surgical margins. OBJECTIVE: Our purpose was to estimate the accuracy of serial transverse cross-sectioning (bread-loafing) at 4-mm intervals in detecting the presence of residual tumor at the margins of well-defined facial basal cell carcinomas excised as an ellipse with 2-mm surgical margins. METHODS: Forty-two small (<1 cm), well-defined, primary, nonmorpheaform facial basal cell carcinomas that had been excised as an ellipse with 2-mm margins and that had positive surgical margins utilizing en-face Mohs sections were included. After longitudinal bisection of each ellipse, frozen sections were prepared encompassing the entire surgical margin. Transparencies with parallel lines spaced at 4-mm intervals were superimposed on the histologic slides with the lines perpendicular to the epidermal surface. Areas in which the lines intersected tumor at the surgical margin were noted. The percentage of tumors that would be detected by serial cross sections was calculated on the basis of the percentage of these parallel lines that intersected tumor. RESULTS: The 42 tumors had a total of 50 positive surgical margins. Overall, the cross-sectional lines intersected tumor 44% of the time (95% confidence interval, 37%-51%). Only 5 (10%) of the residual tumors at the surgical margins exceeded 4 mm in their longitudinal dimension. In the 9 sections containing tumor in the deep margin, tumor intersected the lines 39% of the time. CONCLUSION: Bread-loafing at 4-mm intervals of elliptical excision specimens from facial basal cell carcinomas excised with 2-mm surgical margins is only 44% sensitive in detecting residual tumor at the surgical margins. We recommend complete histologic margin control by using en face tissue orientation (Mohs technique) to identify residual tumor and reduce the risk of tumor recurrence after elliptical excision of facial basal cell carcinomas.

Basal Cell Carcinoma↗

Analysis of motor-vehicle crashes at stop signs in four US cities.

PROBLEM: Nearly 700000 police-reported motor vehicle crashes occur annually at stop signs, and approximately one-third of these crashes involve injuries. The purpose of this study was to develop a better understanding of the crashes that occur at stop signs and to identify potential countermeasures. METHOD: Police reports of crashes at stop sign-controlled intersections during 1996-2000 in four U.S. cities were examined in detail. At total of 1788 crash reports for intersections with two-way stop signs were included in the study. RESULTS: Stop sign violations accounted for about 70% of all crashes. Typically these crashes were angular collisions. Among crashes not involving stop violations, rear-end crashes were most common, accounting for about 12% of all crashes. Stop sign violation crashes were classified into several subtypes - driver stopped, driver did not stop, snow/wet/ice, and other/unknown. In about two-thirds of stop sign violation crashes, drivers said they had first come to a stop. In these cases, inability or failure to see approaching traffic often was cited as the cause of the crash. Drivers younger than 18 as well as drivers 65 and older were disproportionately found to be at fault in crashes at stop signs. IMPACT ON INDUSTRY: Potential countermeasures include changing traffic control and intersection design, improving intersection sight distance, and increasing conspicuity of stop signs through supplemental pavement markings and other devices.

Accidents, Traffic↗

The influence of neighborhood environment on the incidence of childhood asthma: a multilevel approach.

Some ecological analyses suggest an influence of neighborhood environment on asthma outcomes. However, no previous study has applied a multilevel approach to assess an ecological effect of neighborhood environment on the incidence of childhood asthma accounting for individual risk factors. This study assessed the influence of neighborhood and individual-level factors on the incidence of childhood asthma among all children born in Rochester, Minnesota, between 1976 and 1979. We identified asthmatics among all children born in Rochester, between 1976 and 1983. We applied a multilevel survival model with the frailty term to assess the effects of neighborhood characteristics, such as mean family income per census tract (n = 16) from the 1980 census report and the status of whether a census tract faces intersections with major highways or railroads, on asthma incidence. The relative risks (RR) of neighborhood socioeconomic status (SES), the status of whether census tracts face intersections with highways or railroads and the variance of random effect of census tracts were calculated adjusting individual-level covariates for asthma, including gender, birth weight, mother's age at birth and parental educational level at birth. We found that the RR of developing asthma among children living in census tracts facing intersections with highways or railroads was 1.6 (95% CI: 1.1-2.2) compared to those who lived in census tracts not facing intersections, adjusting individual- and neighborhood-level covariates. The variance of the frailty term attributable to census tracts was small (0.0085) and was modified (from 0.004 to 0.0085, 112% change) by adding neighborhood covariates. The overall effects of individual-level factors on asthma incidence were independent of neighborhood environment. The influence of neighborhood environment on childhood asthma in a non-inner-city setting, like Rochester, Minnesota, was small to modest. Incorporating pertinent neighborhood-level covariates into multilevel models needs to be considered in assessing the random effect of clusters.

Asthma↗

Evaluation of an alternative traffic light change anticipation system.

A driving simulator was used to study the efficacy of an alternative signal phasing program. The new Traffic Light Change Anticipation System (TLCAS) utilizes a flashing amber in conjunction with a solid green indication to warn drivers of the impending onset of the solid amber indication. This new program was expected to provide drivers with additional information with which to make safe stopping or crossing decisions, and reduce behaviour associated with increased accident rates at signalized intersections. Additionally, a new measure of first response variability was introduced to evaluate the effect of the new program on driver behavior. The results indicated that the new system has the ability to reduce the number of red light violations. Of the 1148 target intersections, 43 violations were recorded for the regular program compared to 9 for the TLCAS program. The severity of decelerations was also impacted. The regular program displayed average maximum decelerations of 3.1 m/sec2 compared to 2.5 m/sec2 for the TLCAS program. However, the TLCAS program showed an increased variability in first response five times larger than the regular program. This finding, in conjunction with traditional measures, indicates that the new system performs comparably to an increased amber duration by increasing the potential for conflicting decisions between successive drivers approaching an intersection. Altogether, the results suggest that this alternative signal phasing program would not improve intersection safety. The findings also suggest that further study of the longitudinal behavior after the introduction of a TLCAS program may be warranted. Specifically, future studies should examine whether subjects engage in appropriate adaptive changes when confronted with a solid amber period warning after becoming familiar with the TLCAS.

Accidents, Traffic↗

Crash reductions related to traffic signal removal in Philadelphia.

The effect on intersection crashes of converting one-way street intersections in Philadelphia from signal to multiway stop sign control was estimated. Using crash and traffic volume data for a comparison group, regression models were computed to represent the normal crash experience of signal controlled intersections of one-way streets, by impact type, as a function of traffic volume. An empirical Bayesian procedure was used to estimate what would have been the expected number of crashes at the converted intersections had they not been converted. The empirical Bayesian estimates were compared with actual counts of crashes after conversion. Estimates were obtained for different classes of crashes categorized by impact type, day/night condition, and impact severity. Aggregate results indicate that replacing signals by multiway stop signs on one-way streets is associated with a reduction in crashes of approximately 24%, combining all severities, light conditions, and impact types.

Accidents, Traffic↗

An analysis of urban collisions using an artificial intelligence model.

Traditional studies on road accidents estimate the effect of variables (such as vehicular flows, road geometry, vehicular characteristics), and the calculation of the number of accidents. A descriptive statistical analysis of the accidents (those used in the model) over the period 1992-1995 is proposed. The paper describes an alternative method based on the use of artificial neural networks (ANN) in order to work out a model that relates to the analysis of vehicular accidents in Milan. The degree of danger of urban intersections using different scenarios is quantified by the ANN model. Methodology is the first result, which allows us to tackle the modelling of urban vehicular accidents by the innovative use of ANN. Other results deal with model outputs: intersection complexity may determine a higher accident index depending on the regulation of intersection. The highest index for running over of pedestrian occurs at non-signalised intersections at night-time.

Accidents, Traffic↗

Algorithms for computerized QT analysis.

Several methods for measurement of the offset, peak, and morphology of the T wave in multilead ECGs are reviewed and compared. The T wave offset is the most important and also the most difficult measurement for analysis of QT interval dispersion. Measurement methods compared here include (1) the point at which the T wave intersects the isoelectric line plus a threshold; (2) the point at which the derivative of T wave intersects the isoelectric line plus a threshold; (3) the intersection of the maximum slope of the T wave and the isoelectric line; (4) the intersection of a line fitted by least squares to the maximum slope of the T wave and an isoelectric line (LSI); and (5) the point at which the T wave area reaches 90% of the entire T wave area (TA). The reproducibility tests show that the LSI method has the best reproducibility of all the algorithms examined. Although the T wave peak is better defined than the T wave offset, it is not simple to find the right peak when there are multiple T wave peaks and when the T wave is flat and/or noisy. Methods to find T wave patterns with multiple peaks and to locate the point at which the T wave is flat and noisy are therefore reviewed here. Finally, the principal component analysis-based T wave complexity measurement and its relation to other QT interval dispersion measurements are discussed.

Algorithms↗

Temporal constraints on the grouping of contour segments into spatially extended objects.

The speed of contour integration was investigated in a task that can be solved by grouping contour segments into elongated curves. Subjects had to detect a continuous curve, which could be intersected by one or two other curves. At locations where these curves came in close proximity, the assignment of contour segments to the different curves could be based on collinearity. Reaction times exhibited a strong dependence on (1) the presence of intersections among curves; and (2) the context provided by the stimulus set from which individual stimuli were selected. Reaction times were shortest when grouping of contour segments depended on information at a single location in the visual field. In this condition, responses to stimuli containing an intersection were faster than responses to stimuli that did not. When responses were determined by information at spatially separate locations, responses were delayed, and every intersection increased the reaction time considerably. This result contrasts with earlier investigations which have suggested that contour integration on the basis of collinearity is performed pre-attentively but is in accordance with studies on curve tracing. We propose that the assignment of contour segments to equally coherent curves, a process which may be called figure-figure segregation, is a function of object-based attention. Moreover, the protracted reaction times for some of the stimuli indicate that spread of attention within an object costs time. This implies that object recognition is not always as fast as is sometimes assumed.

Attention↗

A simple procedure for quantification of neurite outgrowth based on stereological principles.

The molecular mechanisms controlling formation and remodelling of neuronal extensions are of considerable interest for the understanding of neuronal development and plasticity. Determination of neurite outgrowth in cell culture is a widely used approach to investigate these phenomena. This is generally done by a time consuming tracing of individual neurites and their branches. We have used stereological principles to determine the length of neurites. The total neuritic length per cell was estimated by counting the number of intersections between neurites and test lines of an unbiased counting frame superimposed on images of cell cultures obtained by conventional computer-assisted microscopy. The absolute length, L, of neurites per cell was subsequently estimated from the number of neurite intersections, I, per cell by means of the equation L=(pid/2)I describing the relationship between the number of neurite intersections and the vertical distance, d, between the test lines used. When measuring neurite outgrowth from PC12 cells and primary hippocampal neurons, data obtained by counting neuritic intersections correlated statistically significantly with data obtained using a conventional tracing technique. However, information was acquired more efficiently using the stereological approach. Thus, using the described set-up, the stereological procedure was approximately five times less time consuming than the conventional method based on neurite tracing. The study shows that stereological estimation of neuritic length provides a precise and efficient method for the study of neurite outgrowth in cultures of primary neurons and cell lines.

Animals↗

Accommodation of couch constraints for coplanar intensity modulated radiation therapy.

PURPOSE: Three treatment couches, henceforth referred to as the standard, the variable standard and the C-arm couch, each based on a different supporting frame system, were investigated for their suitability for the delivery of a high number of coplanar beams (> or =5) as may be required for intensity-modulated radiation therapy treatments. MATERIALS AND METHODS: A number of equispaced beam arrangements (five to nine) were examined in combination with two circular target sizes (Phi6 and Phi10 cm) at different locations within an elliptical body on the investigated couches, resulting in 70 different plans per couch. A rule based advisory system determined possible intersections of the beam paths with the supporting frames of the respective treatment couch and suggested a suitable constellation for the supporting frames. In cases of intersection, a beam-couch collision was eliminated by minimal rotation of the beams from the initial equispaced beam arrangement. To investigate the effect of a rotation of the posterior-oblique beams for five, seven and nine initially equispaced beams by an angle of 10 degrees, a prostate plan was generated and compared with equispaced beam arrangement. RESULTS: Initial beam paths intersected with the standard couch in 63% of the plans, necessitating a rotation of one or two beams. It was necessary to modify the beam angles in 34% of the cases on the variable standard couch to avoid an intersection of the beams with the couch. All the plans would have been delivered satisfactorily on the C-arm couch without a rotation of beams. Simulation studies showed that the dose distribution for a prostate treatment could be affected significantly, but not detrimentally, by the rotation of the two posterior-oblique beam orientations by an angle of 10 degrees.

Equipment and Supplies↗