Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets

Qualitative risk assessment methods are often used as the first step to determining design space boundaries; however, quantitative assessments of risk with respect to the design space, i.e., calculating the probability of failure for a given severity, are needed to fully characterize design space boundaries. Quantitative risk assessment methods in design and operational spaces are a significant aid to evaluating proposed design space boundaries. The goal of this paper is to demonstrate a relatively simple strategy for design space definition using a simplified Bayesian Monte Carlo simulation. This paper builds on a previous paper that used failure mode and effects analysis (FMEA) qualitative risk assessment and Plackett-Burman design of experiments to identity the critical quality attributes. The results show that the sequential use of qualitative and quantitative risk assessments can focus the design of experiments on a reduced set of critical material and process parameters that determine a robust design space under conditions of limited laboratory experimentation. This approach provides a strategy by which the degree of risk associated with each known parameter can be calculated and allocates resources in a manner that manages risk to an acceptable level.     

Structure-from-motion by tracking occlusion boundaries

Active visual tracking of points on occlusion boundaries can simplify certain computations involved in determining scene structure and dynamics based on visual motion. Tracking is particularly effective at surface boundaries where large, discontinuous changes in depth are occurring. Two such techniques are described here. The first provides a measure of ordinal depth by distinguishing between occluding and occluded surfaces at a surface boundary. The second can be used to determine the direction of observer motion through a scene.A preliminary version of this material appeared in the Proceedings of the Workshop on Visual Motion, 1989. This work was supported by NSF Grant IRI-8722576     

Imagine Jane and identify John: face identity aftereffects induced by imagined faces

It is not known whether prolonged exposure to perceived and imagined complex visual images produces similar shifts in subsequent perception through selective adaptation. This question is important because a positive finding would suggest that perception and imagery of visual stimuli are mediated by shared neural networks. In this study, we used a selective adaptation procedure designed to induce high-level face-identity aftereffects--a phenomenon in which extended exposure to a particular face facilitates recognition of subsequent faces with opposite features while impairing recognition of all other faces. We report here that adaptation to either real or imagined faces produces a similar shift in perception and that identity boundaries represented in real and imagined faces are equivalent. Together, our results show that identity information contained in imagined and real faces produce similar behavioral outcomes. Our findings of high-level visual aftereffects induced by imagined stimuli can be taken as evidence for the involvement of shared neural networks that mediate perception and imagery of complex visual stimuli.     

Industrial ecology and the boundaries of the manufacturing firm

Decisions on organizational boundaries are critical aspects of manufacturing firms’ business strategies. This article brings together concepts and findings from industrial ecology and business strategy in order to understand how manufacturing firms engage in initiatives to facilitate recycling of process wastes. Based on a distinction between waste recovery and use of the recovered resources, the article introduces a typology of four different strategies: Closed, Outsourcing, Diversification, and Open. Each strategy has a unique set of organizational boundaries and is associated with different motives and benefits for the manufacturing firm. The typology of strategies provides a conceptual contribution to assist industrial managers in strategic decision‐making, and to support further studies on organizational boundaries in industrial ecology research.     

Object Segmentation from Motion Discontinuities and Temporal Occlusions–A Biologically Inspired Model

Background

Optic flow is an important cue for object detection. Humans are able to perceive objects in a scene using only kinetic boundaries, and can perform the task even when other shape cues are not provided. These kinetic boundaries are characterized by the presence of motion discontinuities in a local neighbourhood. In addition, temporal occlusions appear along the boundaries as the object in front covers the background and the objects that are spatially behind it.

Methodology/Principal Findings

From a technical point of view, the detection of motion boundaries for segmentation based on optic flow is a difficult task. This is due to the problem that flow detected along such boundaries is generally not reliable. We propose a model derived from mechanisms found in visual areas V1, MT, and MSTl of human and primate cortex that achieves robust detection along motion boundaries. It includes two separate mechanisms for both the detection of motion discontinuities and of occlusion regions based on how neurons respond to spatial and temporal contrast, respectively. The mechanisms are embedded in a biologically inspired architecture that integrates information of different model components of the visual processing due to feedback connections. In particular, mutual interactions between the detection of motion discontinuities and temporal occlusions allow a considerable improvement of the kinetic boundary detection.

Conclusions/Significance

A new model is proposed that uses optic flow cues to detect motion discontinuities and object occlusion. We suggest that by combining these results for motion discontinuities and object occlusion, object segmentation within the model can be improved. This idea could also be applied in other models for object segmentation. In addition, we discuss how this model is related to neurophysiological findings. The model was successfully tested both with artificial and real sequences including self and object motion.     

Ethnic minorities and brothers in arms: competition and homophily in the military

Although the solidarity of brothers in arms is an important feature of the military, when it comes to ethnic minorities there is a pivotal paradox. On the one hand the military aims at drawing boundaries between soldiers and civilians by blurring existing ethnic and racial divisions inside the military. On the other hand the military is a highly national institution which prides itself on conservative values. Can these contradictions work? And how soldiers understand them? This paper examines the construction of ethnic boundaries in inter-group relations by focusing on the tension between ethnic hierarchy and competition versus homophily – the preference for maintaining ties with persons who are similar. Through participant observation and in-depth interviews with Dutch soldiers before and during deployment in Bosnia and Kosovo I ask when each strategy is put into work and why.     

Neural mechanisms of human texture processing: texture boundary detection and visual search

Texture of various appearances, geometric distortions, spatial frequency content and densities is utilized by the human visual system to segregate items from background and to enable recognition of complex geometric forms. For automatic, or pre-attentive, segmentation of a visual scene, sophisticated analysis and comparison of surface properties over wide areas of the visual field are required. We investigated the neural substrate underlying human texture processing, particularly the computational mechanisms of texture boundary detection. We present a neural network model which uses as building blocks model cortical areas that are bi-directionally linked to implement cycles of feedforward and feedback interaction for signal detection, hypothesis generation and testing within the infero-temporal pathway of form processing. In the spirit of Jake Beck's early investigations our model particularly builds upon two key hypotheses, namely that (i) texture segregation is based on boundary detection, rather than clustering homogeneous items, and (ii) texture boundaries are detected mainly on the basis of larger scenic contexts mediated by higher cortical areas, such as area V4. The latter constraint provides a basis for element grouping in accordance to the Gestalt laws of similarity and good continuation. It is shown through simulations that the model integrates a variety of psychophysical findings on texture processing and provides a link to the underlying physiology. The functional role of feedback processing is demonstrated by context dependent modulation of V1 cell activation, leading to sharply localized detection of texture boundaries. It furthermore explains why pre-attentive processing in visual search tasks can be directly linked to texture boundary processing as revealed by recent EEG studies on visual search.     

Factors affecting the recognition of territory boundaries by mice (Mus musculus)

Male mice of the LACA strain and from a wild stock were allowed to form territories in 180-cm² enclosures. The clues by which they recognized the position of the territory boundaries were investigated by moving various landmarks or reference objects. The information used was found to be primarily visual, close objects taking precedence over distant ones. Olfactory clues were also used but only when they did not conflict with the visual ones. Cover was found to be necessary for territory formation, but not for maintenance, and the size of the territory apparently influenced the aggressiveness of the mouse holding it.     

Axonal processes and neural plasticity. III. Competition for dendrites.

In previous work we have developed a computational framework for topographic map formation and plasticity based on axonal process sprouting and retraction, in which sprouting and retraction are governed by competition for neurotrophic support. Here we show that such an approach can account for certain aspects of the dendritic morphology of cortical maps. In particular, we model the development of ocular dominance columns in the primary visual cortex and show that cortical cells near to column boundaries prefer to elaborate dendritic fields which avoid crossing the boundaries. This emerges as different functional inputs are spatially separated. We predict that afferent segregation occurs before or simultaneously with, but not after, the emergence of dendritic bias. We predict that animals reared with complete but asynchronous stimulation of the optic nerves do not develop a dendritic bias. We suggest that the emergence of a dendritic bias might provide a partial account for the critical period for a response to monocular deprivation. In particular, we predict that animals reared with asynchronous optic nerve stimulation might exhibit an extended critical period. Our results also indicate that the number of synapses supported by cortical cells depends on the intra-ocular image correlations used in our simulations. This suggests that inter-ocular image correlations, and thus strabismic rearing of kittens, may also affect the innervation density.     

Fucntional specialization and binocular interaction in the visual areas of rhesus monkey prestriate cortex.

If is is believed that neural mechanisms mediating stereoscopic vision may be localized in specific areas of the visual cortex, then it becomes necessary to be able to define these areas adequately. This is no easy matter in the rhesus monkey, an animal close to man, where the cytoarchitecturally uniform prestriate cortex is folded into deep sulci with secondary gyri. One way around this awkward problem is to use the callosal connections of the prestriate cortex as the anatomical landmarks. Callosal connections are restricted to regions at which the vertical meridian is represented. Since the visual fields, including the vertical meridian, are separately represented in each area, each has its own callosal connections. These are of great help in defining some of the boundaries of these areas, since the boundaries often coincide with the representation of the vertical meridian. With the visual areas thus defined anatomically, it becomes relatively easy to assign recordings to particular areas. Studies of binocular interactions in these areas reveal that most cells in all prestriate areas are binocularly driven. Hence, theoretically, all of the prestriate areas are candidates for stereoscopic mechanisms. The degree of binocular interaction varies from cell to cell. At the two extremes are cells which either respond to monocular stimulation only and are inhibited by binocular stimulation or ones which respond to binocular stimulation only. Changing, as opposed to fixed, disparity is signalled by two types of cells. In one category are cells activated in opposite directions for the two eyes. Such cells are always binocularly driven. In the other category are cells, some of which are monocularly activated, that are capable of responding to changing image size. In the monkey, both these categories of cells have so far been found in the motion area of the superior temporal sulcus only.     

On the role of medial geometry in human vision.

A key challenge underlying theories of vision is how the spatially restricted, retinotopically represented feature analysis can be integrated to form abstract, coordinate-free object models. A resolution likely depends on the use of intermediate-level representations which can on the one hand be populated by local features and on the other hand be used as atomic units underlying the formation of, and interaction with, object hypotheses. The precise structure of this intermediate representation derives from the varied requirements of a range of visual tasks which motivate a significant role for incorporating a geometry of visual form. The need to integrate input from features capturing surface properties such as texture, shading, motion, color, etc., as well as from features capturing surface discontinuities such as silhouettes, T-junctions, etc., implies a geometry which captures both regional and boundary aspects. Curves, as a geometric model of boundaries, have been extensively used as an intermediate representation in computational, perceptual, and physiological studies, while the use of the medial axis (MA) has been popular mainly in computer vision as a geometric region-based model of the interior of closed boundaries. We extend the traditional model of the MA to represent images, where each MA segment represents a region of the image which we call a visual fragment. We present a unified theory of perceptual grouping and object recognition where through various sequences of transformations of the MA representation, visual fragments are grouped in various configurations to form object hypotheses, and are related to stored models. The mechanisms underlying both the computation and the transformation of the MA is a lateral wave propagation model. Recent psychophysical experiments depicting contrast sensitivity map peaks at the medial axes of stimuli, and experiments on perceptual filling-in, and brightness induction and modulation, are consistent with both the use of an MA representation and a propagation-based scheme. Also, recent neurophysiological recordings in V1 correlate with the MA hypothesis and a horizontal propagation scheme. This evidence supports a geometric computational paradigm for processing sensory data where both dynamic in-plane propagation and feedforward-feedback connections play an integral role.     

The role of attention in figure-ground segregation in areas V1 and V4 of the visual cortex

Our visual system segments images into objects and background. Figure-ground segregation relies on the detection of feature discontinuities that signal boundaries between the figures and the background and on a complementary region-filling process that groups together image regions with similar features. The neuronal mechanisms for these processes are not well understood and it is unknown how they depend on visual attention. We measured neuronal activity in V1 and V4 in a task where monkeys either made an eye movement to texture-defined figures or ignored them. V1 activity predicted the timing and the direction of the saccade if the figures were task relevant. We found that boundary detection is an early process that depends little on attention, whereas region filling occurs later and is facilitated by visual attention, which acts in an object-based manner. Our findings are explained by a model with local, bottom-up computations for boundary detection and feedback processing for region filling.     

A multi-differential neuromorphic approach to motion detection

This paper presents a multi-differential neuromorphic approach to motion detection. The model is based evidence for a differential operators interpretation of the properties of the cortical motion pathway. We discuss how this strategy, which provides a robust measure of speed for a range of types of image motion using a single computational mechanism, forms a useful framework in which to develop future neuromorphic motion systems. We also discuss both our approaches to developing computational motion models, and constraints in the design strategy for transferring motion models to other domains of early visual processing.     

Mathematical requirements of visual–vestibular integration

This article addresses the intersection between perceptual estimates of head motion based on purely vestibular and purely visual sensation, by considering how nonvisual (e.g. vestibular and proprioceptive) sensory signals for head and eye motion can be combined with visual signals available from a single landmark to generate a complete perception of self-motion. In order to do this, mathematical dimensions of sensory signals and perceptual parameterizations of self-motion are evaluated, and equations for the sensory-to-perceptual transition are derived. With constant velocity translation and vision of a single point, it is shown that visual sensation allows only for the externalization, to the frame of reference given by the landmark, of an inertial self-motion estimate from nonvisual signals. However, it is also shown that, with nonzero translational acceleration, use of simple visual signals provides a biologically plausible strategy for integration of inertial acceleration sensation, to recover translational velocity. A dimension argument proves similar results for horizontal flow of any number of discrete visible points. The results provide insight into the convergence of visual and vestibular sensory signals for self-motion and indicate perceptual algorithms by which primitive visual and vestibular signals may be integrated for self-motion perception.     

The use of visual information by house flies,Musca domestica (Diptera: Muscidae), foraging in resource patches

Summary House flies, Musca domestica, respond to visual contrasts on the substrate if a resource is associated with the contrasting patterns. Visible resource patch boundaries serve as a signal to flies that they are about to leave a rewarding patch. Searching flies respond to such visual information by walking along the resource patch boundary and turning back into the patch at its edge. This edge detection and response serve as a mechanism for flies with visual cues to stay in a rewarding patch and locate more resources within it. The intensity of their response correlates with the quality of the resource. In the absence of visual cues, patch shape affects foraging success; flies find more resources in circular than in linear resource distributions. The effects of visual cues, however, render patch shape unimportant. Various substrate contrasts are effective as resource information for flies: dark (e.g., green) figures on bright (e.g., white) backgrounds or bright figures on dark backgrounds. Responses to substrate contrasts measured in this study indicate that, over the short term, house flies can learn a visual cue associated with a food source.     

Pre-attentive segmentation in the primary visual cortex

The activities of neurons in primary visual cortex have been shown to be significantly influenced by stimuli outside their classical receptive fields. We propose that these contextual influences serve pre-attentive visual segmentation by causing relatively higher neural responses to important or conspicuous image locations, making them more salient for perceptual pop-out. These locations include boundaries between regions, smooth contours, and pop-out targets against backgrounds. The mark of these locations is the breakdown of spatial homogeneity in the input. for instance, at the border between two texture regions of equal mean luminance. This breakdown causes changes in contextual influences, often resulting in higher responses at the border than at surrounding locations. This proposal is implemented in a biologically based model of VI in which contextual influences are mediated by intra-cortical horizontal connections. The behavior of the model is demonstrated using examples of texture segmentation, figure-ground segregation, target-distractor asymmetry, and contour enhancement, and is compared with psychophysical and physiological data. The model predicts (1) how neural responses should be tuned to the orientation of nearby texture borders, (2) a set of qualitative constraints on the structure of the intracortical connections, and (3) stimulus-dependent biases in estimating the locations of the region borders by pre-attentive vision.     

Projection pursuit nonparametric regression applied to field counts of the aphid Macrosiphum euphorbiae (Homoptera: Aphididae) on tomato crops in greenhouses

The number of plants that sampling requires in aphid population studies often exceeds one hundred. Thus, only quick and nondestructive methods can be used to sample this pest in a reasonable time interval. We propose a visual method for estimating the density of the aphid Macrosiphum euphorbiae (Thomas) on tomato plants reared in greenhouses. After approximately 1min of visual observation plants can be assigned to abundance classes, the boundaries of which are roughly the powers of square root 10. Precise counts were collected simultaneously on sets of reference plants from the same greenhouse. Projection pursuit nonparametric regression was then used to provide unbiased estimates of aphid densities from the abundance classes and several easily gathered explanatory variables. The robustness of the method was evaluated by testing the models on the complementary data sets from plants in which the aphid densities were precisely counted. In both single and twin-row cultural conditions, for the reference and complementary data sets, the order of magnitude of the error was less than one class rank per plant. The investigation time was reduced by approximately 10-fold compared with the exact counting method. This easy-to-teach field method could be useful in large-scale population surveys and for optimizing integrated pest management strategies.     

Interactions between national and local strategies for the management of aquatic weeds

Management of aquatic weeds is often handled primarily at the local level. However, both water and water weeds do not recognise political boundaries even when these coincide with rivers or catchment areas. Thus potentially effective management of a weed in one area may be undermined by absence of a complementary program of management in an adjacent area. Authorities in each of the eight States or Territories that make up Australia are separately responsible for managing water weeds in their own State or Territory. Originally there was little coordination of these programs, but during the 1980s a national strategy for control of Australian water weeds has been progressively devised and put into practice. This stresses prevention and includes policies on plant importation, nomination of noxious weeds, development of a research strategy, a public awareness campaign, guidelines on the use of herbicides in or near water, and a field guide. This strategy is currently being incorporated into a National Weeds Strategy.     

Aging, visual information, and adaptation to task asymmetry in bimanual force coordination

This study investigated the coordination and control strategies that the elderly adopt during a redundant finger force coordination task and how the amount of visual information regulates the coordination patterns. Three age groups (20-24, 65-69, and 75-79 yr) performed a bimanual asymmetric force task. Task asymmetry was manipulated via imposing different coefficients on the finger forces such that the weighted sum of the two index finger forces equaled the total force. The amount of visual information was manipulated by changing the visual information gain of the total force output. Two hypotheses were tested: the reduced adaptability hypothesis predicts that the elderly show less degree of force asymmetry between hands compared with young adults in the asymmetric coefficient conditions, whereas the compensatory hypothesis predicts that the elderly exhibit more asymmetric force coordination patterns with asymmetric coefficients. Under the compensatory hypothesis, two contrasting directions of force sharing strategies (i.e., more efficient coordination strategy and minimum variance strategy) are expected. A deteriorated task performance (high performance error and force variability) was found in the two elderly groups, but enhanced visual information improved the task performance in all age groups. With low visual information gain, the elderly showed reduced adaptability (i.e., less asymmetric forces between hands) to the unequal weighting coefficients, which supported the reduced adaptability hypothesis; however, the elderly revealed the same degree of adaptation as the young group under high visual gain. The findings are consistent with the notion that the age-related reorganization of force coordination and control patterns is mediated by visual information and, more generally, the interactive influence of multiple categories of constraints.