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PubMed2001

The geometry of shape space: application to influenza.

Shape space was proposed over 20 years ago as a conceptual formalism in which to represent antibody/antigen binding. It has since played a key role in computational immunology. Antigens and antibodies are considered to be points in an abstract "shape space", where coordinates of points in this space represent generalized physico-chemical properties associated with various (unspecified) physical properties related to binding, such as geometric shape, hydrophobicity, charge, etc. Distances in shape space between points representing antibodies and (the shape complement) of antigens are assumed to be related to their affinity, with small distances corresponding to high affinity. In this paper, we provide algorithms, related to metric and ordinal multidimensional scaling algorithms first developed in the mathematical psychology literature, which construct explicit, quantitative coordinates for points in shape space given experimental data such as hemagglutination inhibition assays, or other general affinity assays. Previously, such coordinates had been conceptual constructs and totally implicit. The dimension of shape space deduced from hemagglutination inhibition assays for influenza is low, approximately five dimensional. The deduction of the explicit geometry of shape space given experimental affinity data provides new ways to quantify the similarity of antibodies to antibodies, antigens to antigens, and the affinity of antigens to antibodies. This has potential utility in, e.g. strain selection decisions for annual influenza vaccines, among other applications. The analysis techniques presented here are not restricted to the analysis of antibody-antigen interactions and are generally applicable to affinity data resulting from binding assays.

Algorithms↗
PubMed2001

The topology of the possible: formal spaces underlying patterns of evolutionary change.

The current implementation of the Neo-Darwinian model of evolution typically assumes that the set of possible phenotypes is organized into a highly symmetric and regular space equipped with a notion of distance, for example, a Euclidean vector space. Recent computational work on a biophysical genotype-phenotype model based on the folding of RNA sequences into secondary structures suggests a rather different picture. If phenotypes are organized according to genetic accessibility, the resulting space lacks a metric and is formalized by an unfamiliar structure, known as a pre-topology. Patterns of phenotypic evolution-such as punctuation, irreversibility, modularity--result naturally from the properties of this space. The classical framework, however, addresses these patterns by exclusively invoking natural selection on suitably imposed fitness landscapes. We propose to extend the explanatory level for phenotypic evolution from fitness considerations alone to include the topological structure of phenotype space as induced by the genotype-phenotype map. We introduce the mathematical concepts and tools necessary to formalize the notion of accessibility pre-topology relative to which we can speak of continuity in the genotype-phenotype map and in evolutionary trajectories. We connect the factorization of a pre-topology into a product space with the notion of phenotypic character and derive a condition for factorization. Based on anecdotal evidence from the RNA model, we conjecture that this condition is not globally fulfilled, but rather confined to regions where the genotype-phenotype map is continuous. Equivalently, local regions of genotype space on which the map is discontinuous are associated with the loss of character autonomy. This is consistent with the importance of these regions for phenotypic innovation. The intention of the present paper is to offer a perspective, a framework to implement this perspective, and a few results illustrating how this framework can be put to work. The RNA case is used as an example throughout the text.

Animals↗
PubMed1994

Water and electrolyte studies during long-term missions onboard the space stations SALYUT and MIR.

This contribution summarizes the results of investigations of water-electrolyte metabolism and its hormonal regulation conducted in cosmonauts who performed long-term space flights (from 18 to 366 days) aboard the space stations Salyut and Mir and compares them with the results obtained during various NASA flights. The role of the kidneys in ion metabolism regulation was assessed by various water-salt load tests before and after flights. In addition, the results of a year-long space flight and of medical experiments performed during the 237- and 241-day missions by the physicians and cosmonaut-researchers Atkov and Polyakov are reviewed in detail. In spite of interindividual variations, metabolic, and endocrine studies during prolonged space flights showed a reduction in body mass, usually with a reduction in body water and electrolytes and considerable changes in blood hormone concentrations and urinary hormone excretion. These changes reflect the processes of extended adaptation to a new environment. It is likely that shifts in electrolyte metabolism in weightlessness are primarily due to metabolic changes that diminish the tissue ability for ion retention and to concomitant changes in the endocrine status. The postflight examinations revealed changes in fluid-electrolyte metabolism and in the function of the kidneys which indicated a hypohydration status and a stimulation of hormonal systems responsible for fluid-electrolyte homeostasis in order to readapt to the normal gravitation. Postflight decline in osmotic concentration of urine in cosmonauts was accompanied by an altered response to antidiuretic hormone and was probably caused by changes in the functional state of the kidneys. We conclude that detailed knowledge of the alterations in water-electrolyte metabolism and its hormonal regulation on different stages of space flight are important prerequisites for the development of countermeasures to space deconditioning and thus for increased human efficiency in space. In addition, these data contribute to an increase in our general knowledge on the regulation of kidney function.

Aerospace Medicine↗
PubMed1996

Functional gliding spaces of the dorsal side of the human finger.

Although the clinical and functional importance of gliding and connective tissue spaces has been repeatedly emphasized (e.g. their role in the spreading of suppurative phlegmonic inflammation) only few literary findings can be presented dealing with the connective tissue spaces in the finger in the metacarpo-phalangeal transition region. Three separate gliding spaces of the finger above the dorsal aponeurosis and their various regional connections can be displayed by means of a plastic injection technique followed by plastination and production of sectional series. These gliding spaces were also examined on fixed and unfixed hands using plastic injection and subsequent dissection. A space was depicted between the proximal interphalangeal joint and the insertion of the dorsal aponeurosis on the distal phalanx of the finger, as well as a further bursa-like space over the proximal interphalangeal joint. A third space was also depicted between the metacarpophalangeal joint and the proximal interphalangeal joint, which displays a variable connection to the gliding canal of the respective extensor tendons. Methodical, functional and clinical aspects will be discussed.

Cadaver↗
PubMedDate not supplied

Right anterior subphrenic space: an important site for the early detection of intraperitoneal fluid on abdominal CT.

BACKGROUND: Small rinds of free fluid are frequently seen in the right anterior subphrenic space. Therefore, we investigated patients undergoing abdominal computed tomography (CT) to see whether early fluid collections are seen preferentially at this or any other site. METHODS: CT examinations of 59 randomly selected patients with minor or moderate quantities of free intraperitoneal fluid were analyzed. The location of the fluid was determined [subphrenic spaces, the right hepatorenal fossa (Morison's pouch), paracolic gutters, pelvis (pouch of Douglas)]. The amount of fluid in each location was subjectively quantified (none, trace, small, or moderate). RESULTS: Free fluid was seen most frequently in the right anterior subphrenic space (44/59 patients, 75%) and pelvis (43/59 patients, 73%). Eight patients had intraperitoneal fluid at an isolated location (three in the pelvis alone, two in the left subphrenic space, one in the right subphrenic space, and one in each of the right and left paracolic spaces). CONCLUSIONS: Contrary to popular belief, intraperitoneal fluid is not always seen first in the pelvis when the patient is in the supine position. Although fluid is not consistently seen first in any specific location, the subphrenic space (especially the right anterior) is a common site where small quantities of fluid may be identified.

Adolescent↗
PubMed1999

The Economic Value of Open Space: A Review and Synthesis.

/ Communities increasingly face development pressures that can irreversibly alter open space lands. While the monetary costs and benefits of development are typically known, the corresponding values of natural lands are complex and difficult to measure. This paper reviews different concepts of economic value in relation to open space, describes methods for quantifying these values, and presents examples of each from published literature. Open space benefits accruing to citizens as market values or consumers' surplus include market and enhancement values, production values, natural systems value, use and nonuse values, and various intangible values. Economic impacts that open space lands have on local communities and economies include fiscal impacts on municipal budgets, expenditures from open space-related activities, and impacts from employment and tax revenues. These values are not universally present within a given community, nor are they quantitatively additive. However, a comprehensive consideration of the multiple values of open space will better inform community decisions about land conservation and development. KEY WORDS: Conservation; Economic value; Land use; Open space; Zoning

Journal Article↗
PubMed1988

The distance from the skin to the epidural space.

To determine whether there is any systemic relationship between the distance from the skin to the epidural space and physical constitution, the distance from the skin to the epidural space was measured in 1007 epidural punctures. The distance from the skin to the epidural space in male was greater than that in female ( P << 0.001). However, the analysis of the distance from the skin to the epidural space of the selected patients who had both a weight of 50-60 kg and a height of 1.5-1.7 m indicated no statistical difference between male and female. The best correlation was found between the distance from the skin to the epidural space and body weight. The correlation between the distance from the skin to the epidural space and height was less striking. Ninety-five percent of the patients who received epidural puncture at the thoraco-cervical area (C7-T2) had a distance to the epidural space of 4.0-6.9 cm; 87% at the lower-thoracic area (T8-T10), 4.0-6.9 cm; 93% at the thoraco-lumbar area (T12-L2), 3.0-4.9 cm; 85% at the mid-lumbar area (L2-L4), 3.0-4.9 cm. These results may be useful for young anesthesiologists to master epidural block safely and efficiently.

Journal Article↗
PubMed1984

The effects of space closure of the mandibular first molar area in adults.

There is little information regarding the orthodontic closure of remodeled, edentulous spaces in the posterior area of the mandible. The present study was undertaken to determine the dental and periodontal changes that occur when mandibular first molar areas are closed in adults. Fourteen adult patients were selected from private orthodontic practices. Pre- and posttreatment study models were used to measure the mesiodistal length of the edentulous space and the buccolingual width of the alveolar ridge. The amount of crown and root movement of the second molar and premolar was measured from lateral cephalometric radiographs. From pre- and posttreatment panoramic or periapical radiographs, the anatomic changes of the second molar and adjacent periodontium were also measured. Every case showed significant space closure (x = 6.2 mm) ranging from 2.7 to 11.5 mm. There was crestal bone loss (x = 1.3 mm) mesial to the second molar in all but five cases. These latter cases showed bone addition. As the molar moved mesially , the alveolar ridge increased in width an average of 1.2 mm. The adult patient who showed the greatest amount of space closure and the least amount of molar bone loss had (1) mesiodistal space of 6.0 mm, (2) buccolingual ridge width of 7.0 mm, and (3) mesial molar bone level 1.0 mm apical to the cementoenamel junction. The results of this study indicate that space closure is not only possible but may aid the treatment of certain cases. Space closure should be considered as a potential solution to the absence of mandibular first permanent molars.

Adult↗
PubMed1994

Effect of lung inflation and sternotomy direction on pleural space violation.

Patients often are disconnected temporarily from the ventilator before sternotomy to avoid entering the pleural space with the sternal saw. Although this practice is widespread, it is based on questionable physiologic principles. To evaluate the efficacy of this maneuver in reducing the incidence of pleural space violation with first-time sternotomy, 126 cardiac patients were randomized prospectively to either lungs inflated or deflated during sternotomy with the surgeon blinded to the particular assignment. The incidence of pleural space violation overall was 12%, occurring in 15% of patients with deflated lungs and in 9% of those with inflated lungs (p = 0.455 by chi 2 test). Examining the effect of the direction of sternotomy on pleural space entry revealed a 4% incidence with sternotomy starting at the xiphoid versus a 21% incidence with sternotomy starting at the sternal notch (p = 0.009 by chi 2 test). Preexisting hyperinflation of the lungs as evaluated by chest radiograms did not influence the incidence of pleural space violation. To reduce pleural space violation, sternotomy should be performed from the xiphoid to the sternal notch. More importantly, disconnecting the patient from the ventilator does not reduce pleural space violation with sternotomy and its further use is not indicated. These findings are discussed in the context of relevant heart-lung pathophysiology.

Cardiac Surgical Procedures↗
PubMed1989

The relationship between eggshell porosity and air space gas tensions measured before and during the parafoetal period and their effects on the hatching process in the domestic fowl.

The partial pressure of gases in the air space were measured before and during the parafoetal period for domestic fowl eggs of the same initial weight but varying in eggshell conductance. Embryos developed and hatched normally from eggs with a wide range of shell conductance and resultant air space gas partial pressures. Air space PO2 levels measured just before pipping ranged from 55 to 65 mm Hg in low and high conductance eggs, respectively, whilst PCO2 levels ranged from 75 to 55 mm Hg. With increasing shell conductance embryos membrane-penetrated and pipped the shell later, but hatch time was unaffected. Membrane penetration and external pipping appeared to occur in response to the partial pressures of gas in the air space but not in response to one particular level of air space PO2 or PCO2. During the parafoetal stage air space PO2 decreased at about 3.8 mm Hg/h and air space PCO2 increased at about 1.8 mm Hg/h and these rates of change were unaffected by eggshell conductance.

Animals↗
PubMed1993

Space in its place: developing the link in medical geography.

This paper argues that a re-examination of the interrelationship between constructs of place and space is crucial to geography's involvement in the broader endeavour of health research. Place has re-emerged as nexus of ascribed meaning within contemporary social theory. Places, however, are related in space, by distance or proximity. The distinction needs to be made between this orthodox (geometric) view of space and two types of social space: the (experienced) space described by humanist geographers; and the more recent (socio-spatial) conceptualization which is both experienced and (re)produced by societal structures and advocated by social theorists in geography. We argue that advancing a recursive understanding of space and place is an appropriate direction in medical geography. This direction will include both an understanding of the ways in which space shapes the character of places and how the particularities of places resist or set in motion (orthodox) spatial processes. Illustrations are drawn from studies of mental illness and mental health care and primary health care in a remote area of New Zealand.

Cross-Cultural Comparison↗
PubMed1993

A computer-aided study of speaking spaces.

A computer-aided system was devised to investigate the speaking space. Thirty native Cantonese speakers with Class I occlusion were selected and test sentences were designed for speech analysis by a Sona-Graph. The investigation indicated that the sibilant sounds produced the closest speaking space and that the mean and the variability of the closest speaking space in Cantonese speakers were smaller than that in English speakers. The beliefs that the closest speaking space was smaller than that of the freeway space and that the speaking space of m sound was similar to the freeway space were not supported by this study.

Adult↗
PubMed2005

Improved detectability of experimental allergic encephalomyelitis in excised swine spinal cords by high b-value q-space DWI.

Experimental allergic encephalomyelitis (EAE) is the primary experimental model of multiple sclerosis (MS), which involves both inflammation and demyelination and is known to be species-dependent. Spinal cord abnormalities were found in more than 80% of postmortem specimens of MS patients. In the present study, T1, T2 and high b-value q-space diffusion-weighted magnetic resonance imaging (MRI) were used, for the first time, to characterize the EAE model in excised swine spinal cords. The MR images were compared with histological staining and clinical scoring. Although all spinal cords were excised from swine with severe or very severe (clinical score between 3 to 5 on a scale of 5) motor impairments, T1- and T2-weighted MRI revealed white matter (WM) abnormalities in only five of the ten EAE diseased spinal cords studied, while high b-value q-space diffusion weighted MRI (q-space DWI) detected WM abnormalities in all diseased spinal cords studied. Interestingly, high b-value q-space DWI was able to detect abnormalities in the normal appearing white matter (NAWM) even in spinal cords where no plaques were identified by the T1- and T2-weighted MR images. Good anatomical correlation was observed between the high b-value q-space MR images and histology. The extent of DWI abnormalities paralleled the clinical scoring and correlated with histology. In addition, areas classified as NAWM by the T1- and T2-weighted MR images that showed abnormalities in the q-space DWI were also found to have abnormal histology. This improved detection level of the EAE model by high b-value q-space DWI over conventional T1-, and T2-weighted MRI is briefly discussed.

Animals↗
PubMed2005

White matter changes in multiple sclerosis: correlation of q-space diffusion MRI and 1H MRS.

OBJECTIVE: To explore the diagnostic usefulness of high b-value diffusion magnetic resonance brain imaging ("q-space" imaging) in multiple sclerosis (MS). More specifically, we aimed at evaluating the ability of this methodology to identify tissue damage in the so-called normal-appearing white matter (NAWM). DESIGN: In this study we examined the correlation between q-space diffusion imaging and magnetic resonance spectroscopy (MRS)-based two-dimensional 1H chemical shift imaging. Eight MS patients with different degree of disease severity and seven healthy subjects were scanned in a 1.5-T magnetic resonance imaging (MRI) scanner. The MRI protocol included diffusion tensor imaging (DTI) (with bmax of 1000 s/mm2), high b-value diffusion-weighted imaging (with bmax of 14,000 s/mm2) and 2D chemical shift imaging. The high b-value data set was analyzed using the q-space methodology to produce apparent displacement and probability maps. RESULTS: We found that the q-space diffusion displacement and probability image intensities correlated well with N-acetylaspartate levels (r=.61 and .54, respectively). Furthermore, NAWM that was abnormal on MRS was also found to be abnormal using q-space diffusion imaging. In these areas, the q-space displacement values increased from 3.8+/-0.2 to 4.6+/-0.6 microm (P<.02), the q-space probability values decreased from 7.4+/-0.3 to 6.8+/-0.3 (P<.002), while DTI revealed only a small, but still significant, reduction in fractional anisotropy values from 0.40+/-0.02 to 0.37+/-0.02 (P<.05). CONCLUSION: High b-value diffusion imaging can detect tissue damage in the NAWM of MS patients. Despite the theoretical limitation of this method, in practice it provides additional information which is clinically relevant for detection of tissue damage not seen in conventional imaging techniques.

Adult↗
PubMed2004

Carotid plaque spaces relate to symptoms and ultrasound scattering.

We have previously found that spectral analysis of ultrasound (US) can discriminate in vitro plaques from asymptomatic and symptomatic (transient ischemic attack within previous 4 weeks) patients. That study found no differences in percentages of lipid or thrombus between the two groups by optical microscopy/planimetry. The present study was to find out if another feature from the microscopy could show a difference. The number and size of spaces resulting from cell death or new blood vessels were measured to see if they related to symptoms or could help explain US differentiation. Twelve plaques from each group were examined by optical microscopy. The sizes and concentrations of two kinds of spaces, endothelial lined (vessel spaces) and unlined (tissue spaces), were correlated both with symptoms and also with the US tissue characterization scores from the previous study. Symptomatic vs. asymptomatic plaques showed a higher concentration and a larger size: 0.87 vs. 0.21 per mm(2) (p < 0.005) and 154 vs. 110 microm (p < 0.02). A discriminant function of spaces with symptoms as dependent variables correctly identified 91.7% of the plaques (p < 0.001). The concentration in plaques previously designated by US as true positive plaques or true negative was 1.21 vs. 0.22 per mm(2) (p < 0.005). spaces were increased in plaques of symptomatic patients and were related to UTC scores. Both the lined and unlined spaces were useful as predictors.

Apoptosis↗
PubMed1998

Comparative observations on the spacing of short-period (von Ebner's) lines in dentine.

The spacing of short-period incremental markings in dentine was measured in longitudinal ground sections and in longitudinal demineralized silver-stained sections of permanent human canines and premolars. Measurements were made (i) within 50 microm from the granular layer of Tomes (GLT), (ii) between 100 and 200 microm from the GLT, and (iii) in the axial plane of the tallest cusps. Median values for the spacing of calcospheritic lines closest to the GLT in the ground sections increased from 1.8 to 2.8 microm as the lines gradually coalesced into a laminar pattern beyond the GLT pulpally. Median values for the spacing of short-period lines in the cuspal dentine, where dentine formation is known to be fastest, were 4.1 microm. Markings in the demineralized sections were between 25 and 39% closer together, presumably due to contraction and shrinkage during specimen preparation. The spacings of short-period incremental lines measured on ground sections of non-human primate dentine (gibbon, siamang, orang) and on pig dentine, all between 100 and 200 microm from the GLT, clustered between 2.5 and 3.5 microm. Apart from gibbon dentine (in which spacings were closer together in this position than in the others), the distribution of measurements was not significantly different in pig, orang or human dentine. However, none of the data for the comparative samples presented here revealed spacings of short-period lines anywhere close to the 16 microm previously reported for circumpulpal dentine in animals. These data suggest that there may be many other animals where the mode and, to some extent, rate of dentine mineralization close to the root surface follows a common pattern. While data for the spacing of incremental markings in dentine provide no evidence for their periodicity, it is clear that the measurements made in the ground sections match the reported daily rates of mineralization at these locations, whereas those in demineralized silver-stained sections do not. Tissue shrinkage is probably a better explanation for this than the generally accepted view that they represent 12 h increments of dentine mineralization. This study provides a better basis for identifying and describing these lines, and for distinguishing them from other kinds of incremental markings in dentine.

Animals↗
PubMed1992

Pattern formation in one- and two-dimensional shape-space models of the immune system.

A large-scale model of the immune network is analyzed, using the shape-space formalism. In this formalism, it is assumed that the immunoglobulin receptors on B cells can be characterized by their unique portions, or idiotypes, that have shapes that can be represented in a space of a small finite dimension. Two receptors are assumed to interact to the extent that the shapes of their idiotypes are complementary. This is modeled by assuming that shapes interact maximally whenever their coordinates in the space-space are equal and opposite, and that the strength of interaction falls off for less complementary shapes in a manner described by a Gaussian function of the Euclidean "distance" between the pair of interacting shapes. The degree of stimulation of a cell when confronted with complementary idiotypes is modeled using a log bell-shaped interaction function. This leads to three possible equilibrium states for each clone: a virgin, an immune, and a suppressed state. The stability properties of the three possible homogeneous steady states of the network are examined. For the parameters chosen, the homogeneous virgin state is stable to both uniform and sinusoidal perturbations of small amplitude. A sufficiently large perturbation will, however, destabilize the virgin state and lead to an immune reaction. Thus, the virgin system is both stable and responsive to perturbations. The homogeneous immune state is unstable to both uniform and sinusoidal perturbations, whereas the homogeneous suppressed state is stable to uniform, but unstable to sinusoidal, perturbations. The non-uniform patterns that arise from perturbations of the homogeneous states are examined numerically. These patterns represent the actual immune repertoire of an animal, according to the present model. The effect of varying the standard deviation sigma of the Gaussian is numerically analyzed in a one-dimensional model. If sigma is large compared to the size of the shape-space, the system attains a fixed non-uniform equilibrium. Conversely if sigma is small, the system attains one out of many possible non-uniform equilibria, with the final pattern depending on the initial conditions. This demonstrates the plasticity of the immune repertoire in this shape-space model. We describe how the repertoire organizes itself into large clusters of clones having similar behavior. These results are extended by analyzing pattern formation in a two-dimensional (2-D) shape-space.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes↗
PubMed1989

The role of perineural space invasion in the local spread of prostatic adenocarcinoma.

In 176 radical prostatectomy specimens areas of capsule penetration by cancer and positive surgical margins were quantified and located over the prostate surface. The presence of cancer within the perineural space was sought in these areas and compared to the normal distribution of prostatic nerve branches. Capsule penetration was found in 78 of 156 stage B carcinomas, and in 39 of these 78 (50 per cent) it occurred entirely by cancer extension through the capsule within perineural spaces. In the remaining 39 prostates capsule penetration by perineural space invasion predominated but direct spread also was found. Most often, perineural space invasion followed the oblique vertical course of nerve branches that extended superiorly to the superior pedicle near the prostate base. In such cases capsule penetration areas were localized near the superior margin of the cancer, and in 11 per cent positive superior pedicle margins resulted from continued perineural space invasion outside the capsule. In cancers near the prostate apex capsule penetration by perineural space invasion produced positive margins in 89 per cent of 18 cases because of the short inferior pedicle. The role of perineural space invasion by cancer was less prominent in 4 of 20 stage A cancers that showed capsule penetration.

Adenocarcinoma↗