Showing papers by "Dalhousie University published in 1991"

A model for development and evolution of complex morphological structures

Abstract: How 'complex' or composite morphological structures like the mammalian craniomandibular region arise during development and how they are altered during evolution are two major unresolved questions in biology. Herein, we have described a model for the development and evolution of complex morphological structures. The model assumes that natural selection acts upon an array of phenotypes generated by variation in a variety of underlying genetic and epigenetic controlling factors. Selection refines the integration of the various morphogenetic components during ontogeny in order to produce a functioning structure and to adapt the organisms to differing patterns of environmental heterogeneity. The model was applied to the development and evolution of the mammalian mandible (which is used as a paradigm of complex morphological structures). The embryology of the mandible was examined in detail in order to identify the fundamental developmental units which are necessary to assemble the final morphological structure. The model is quite general since equivalent units exist for the development of many other biological structures. This model could be applied to many other developing morphological structures as well as other groups of organisms. For example, it can be applied to cell parameters during Drosophila development (Atchley, 1987). The model as discussed in this paper assumes that morphological changes in the mandible result from evolutionary changes in its underlying developmental units. The developmental units relate to characteristics of cellular condensations which are produced from the differentiation of embryonic neural crest cells. The developmental units include: the number of stem cells in preskeletal condensations (n), the time of initiation of condensation formation (t), the fraction of cells that is mitotically active within a condensation (f), the rate of division of these cells (r), and their rate of cell death (d). These units and their derivative structures are discussed in terms of types of tissue differentiation (chondrogenesis, osteogenesis, primary/secondary osteogenesis, intramembranous/endochondral ossification) and growth properties of major morphological regions of the mandible. Variation in these five units provides the developmental basis for ontogenetic and phylogenetic modification of mandibular morphology. We have discussed how these developmental units are influenced by (a) the cell lineage from which they arise, (b) epithelial-mesenchymal (inductive tissue) interactions, (c) regulation of cell differentiation, and (d) extrinsic factors such as muscles, teeth and hormones. Evidence was provided that variation in mandibular morphology is heritable, subject to modification by natural selection, and that divergence among different genetic stocks has apparently occurred through changes in these developmental units and their derivative structures.(ABSTRACT TRUNCATED AT 400 WORDS)

The epidemiology of pain in children and adolescents: a review.

Abstract: Epidemiology is the branch of health science that focuses on investigations of the distribution and determinants of disease or illness in defined populations. Epidemiological studies provide data crucial to the understanding of the etiology, natural history and impact, as well as the aggregation and transmission of a disease or condition. Such studies also document the interrelationships among risk factors associated with the syndrome being investigated. Understanding disorders in these terms is a prerequisite to their prevention and may be invaluable to their treatment. In chronic pain, as in most other chronic disorders, a major aspect of the burden of pain is the resultant changes in lifestyle that often accompany pain. The World Health Organization [65] has developed a model for the impact of diseases that has recently been applied to pain [36]. According to this model, four planes of experience can be described. The first plane is the underlying disease or disorder. The second plane, termed impairment, refers to symptoms including pain. The third plane is disability, which describes those activities that are curtailed as a result of the problem. The fourth plane, handicap, is the restriction of social roles. The relationship between planes of experience is not linear and the different factors influencing pain, disability and handicap are not well understood. Because pain, regardless of etiology, may be associated with extensive disability and handicap, the epidemiology of pain, disability and handicap merits considerable attention. Epidemiological studies of disability

The Saccharomyces cerevisiae MYO2 gene encodes an essential myosin for vectorial transport of vesicles.

Abstract: After the initiation of bud formation, cells of the yeast Saccharomyces cerevisiae direct new growth to the developing bud. We show here that this vectorial growth is facilitated by activity of the MYO2 gene. The wild-type MYO2 gene encodes an essential form of myosin composed of an NH2-terminal domain typical of the globular, actin-binding domain of other myosins. This NH2-terminal domain is linked by what appears to be a short alpha-helical domain to a novel COOH-terminal region. At the restrictive temperature the myo2-66 mutation does not impair DNA, RNA, or protein biosynthetic activity, but produces unbudded, enlarged cells. This phenotype suggests a defect in localization of cell growth. Measurements of cell size demonstrated that the continued development of initiated buds, as well as bud initiation itself, is inhibited. Bulk secretion continues in mutant cells, although secretory vesicles accumulate. The MYO2 myosin thus may function as the molecular motor to transport secretory vesicles along actin cables to the site of bud development.

Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster

Abstract: The synaptic connections within the lamina, the first of the optic neuropiles underlying the insect's compound eye, have been little studied in Drosophila melanogaster until now, despite the genetic advantages of this animal. Here we report the reconstruction through its entire depth of one of the lamina modules, or cartridges, of a female wild-type Drosophila, for which a series of EM cross sections was analysed at levels extending from the retinal basement membrane to the first optic chiasma. A complete, comprehensive catalogue of the synaptic connections of all columnar elements has been compiled from this single series, confirmed from comparisons with less completely photographed cartridges. Combinations of the 12 types of cartridge neurons form divergent multiple-contact synapses (dyads, triads, and tetrads) throughout the lamina's depth. These 12 neuron types include 11 narrow-field elements (one class of receptor terminal, R1–R6, providing input to the cartridge; two types of long visual fiber from the ommatidium, R7 and R8; five types of monopolar cell, L1–5; and three types of medulla cell–two centrifugal neurons C2 and C3, and a third, T1) as well as a wide-field intrinsic or amacrine cell. Connections within the lamina formed by L4 from two adjacent cartridges (posterodorsal and posteroventral) contribute to the matrix of connections. In addition, connections of at least one other wide-field element have also been incorporated.

Do more constraints mean less leisure? Examining the relationship between constraints and participation.

Abstract: Underlying much of the literature on leisure constraints is the assumption that the constraints that people report do, in fact, act as barriers to participation. However, to date, there has been a ...

Directive interactions and early vocabulary development: the role of joint attentional focus.

Abstract: Maternal directiveness, assessed by the mother's use of prescriptives, is correlated with slow vocabulary development. As prescriptives are most often used to redirect a child's attention to a different object or activity, it is hypothesized that attentional regulation underlies this negative relationship. In the present study, twelve mothers were videotaped interacting with their children aged 1;1, and 100 maternal utterances were coded for pragmatic intent. Prescriptives were coded as either changing (leading) or following the child's focus of attention. Only the frequency of mothers' follow-prescriptives correlated significantly with a productive vocabulary measure taken at 1;10. This correlation was high and positive, indicating that, given joint focus, directing a 13-month-old's behaviour can have beneficial effects on subsequent vocabulary development.

Kinetic theory for granular flow of dense, slightly inelastic, slightly rough spheres

Abstract: A general set of conservation equations and constitutive integrals for the dynamic properties of the rapid flow of a granular material consisting of slightly inelastic and slightly rough spherical particles is derived by following an approach used in the kinetic theory of dense gases. By taking moments of the translational and rotational particle velocities in the general transport moment equation and making the Enskog approximation, the singlet velocity distribution function is determined. As a result, the constitutive relations and coefficients such as stresses, energy fluxes, rates of translational and rotational energy interchanges, shear viscosity, spin viscosity, bulk viscosity and ‘thermal’ conductivities are obtained. The present theory incorporates the kinetic as well as the collisional contributions for stresses and energy fluxes. Thus, it is appropriate for dilute as well as dense concentrations of solids. For the case of simple shear flow, there is favourable agreement between the theoretical predictions of stresses and both the experimental measurements and the results from computer simulations.

Cryptomonad algae are evolutionary chimaeras of two phylogenetically distinct unicellular eukaryotes.

Abstract: ALTHOUGH it is widely accepted that the plastids of plants and algae originated as endosymbionts1, the details of this evolutionary process are unclear2'3. It has been proposed that in organisms whose plastids are surrounded by more than two membranes, the endosymbiont was a eukaryotic alga rather than a photosynthetic prokaryote4. The DNA-containing5 nucleomorph6 of cryptomonad algae appears to be the vestigial nucleus of such an algal endosymbiont7. Eukaryotic-type ribosomal RNA sequences have been localized to a nucleolus-like structure in the nucleomorph8. In support of the hypothesis that cryptomonads are evolutionary chimaeras of two distinct eukaryotic cells, we show here that Cryptomonas Φ contains two phylogenetically separate, nuclear-type small-subunit rRNA genes, both of which are transcriptionally active. We incorporate our rRNA sequence data into phylogenetic trees, from which we infer the evolutionary ancestry of the host and symbiont components of Cryptomonas Φ. Such trees do not support the thesis3 that chromophyte algae evolved directly from a cryp-tomonad-like ancestor.

A segment interaction analysis of proximal-to-distal sequential segment motion patterns

Abstract: The purpose of this study was to examine the motion-dependent interaction between adjacent lower extremity segments during the actions of kicking and the swing phases of running and walking. This was done to help explain the proximal-to-distal sequential pattern of segment motions typically observed in these activities and to evaluate general biomechanical principles used to explain this motion pattern. High speed film data were collected for four subjects performing each skill. Equations were derived which expressed the interaction between segments in terms of resultant joint moments at the hip and knee and several interactive moments which were functions of gravitational forces or kinematic variables. The angular motion-dependent interaction between the thigh and leg was found to play a significant role in determining the sequential segment motion patterns observed in all three activities. The general nature of this interaction was consistent across all three movements except during phases in which there were large differences in the knee angle. Support was found for the principle of summation of segment speeds, whereas no support was found for the principle of summation of force or for general statements concerning the effect of negative thigh acceleration on positive leg acceleration. The roles played by resultant joint moments in producing the observed segment motion sequences are discussed.

Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model.

Abstract: Changes in nerve fiber numbers distal to a nerve repair in the sciatic nerve of 48 rats were evaluated over a 1- to 24-month period. The results of the morphometric evaluation in the sciatic nerve distal to the nerve repair demonstrated an increase in nerve fiber counts as early as 1 month following the nerve repair. The number of nerve fibers in the distal nerve was greatest at 3 months and did not return to normal levels until 24 months. The results of this study will influence the timing of experimental studies in which nerve fiber counts are critical for evaluation, and provides a better understanding of the clinical events occurring following nerve repair.

The 'law of bone transformation': a case of crying Wolff?

Abstract: Transformation der Knochen, describing in full his understanding of the link between mechanical loading and bone form, developed from many years of investigation (Wolff, 1868, 1869, 1870, 1874, 1884a, b, 1891, 1892). T h e basis of the work was Wolff's general theory of bone transformation : Every change in the.. . function of a bone.. . is followed by certain definite changes in.. . internal structure and external conformation in accordance with mathematical laws. (Treharne, 198 I ) .

Morphological Variations of Benthic Foraminiferal Tests in Response to Changes in Ecological Parameters - a Review

Abstract: Some of the relatively recent literature correlating morphological variation in benthic foraminifera with environmental parameters such as temperature, salinity, carbonate solubility, depth, nutrition, substrate, dissolved oxygen, illumination, pollution, water motion, trace elements, and rapid environmental fluctuation is reviewed. It appears some variables (most notably depth) are recorded more frequently, which may affect some conclusions. Although each variable is treated separately, it appears that almost no variables act independently on test morphologies. In reviewing the literature, it becomes clear that there are many individual trends, especially with shell ornamentation, but few broad ones, and that it is almost impossible, with exception of some of the larger reef-dwelling, symbiont-bearing foraminifera, to predict how any species will react to various parameters. The broad trends concern thinning or thickening of carbonate tests with changing carbonate availability, temperature, and salinity. It appears that many observations of morphological changes within species may not be recorded in the literature, perhaps because authors did not recognize the importance of small details that would be of importance at a later time.

Biological control of surface temperature in the Arabian Sea

Abstract: In the Arabian Sea, the southwest monsoon promotes seasonal upwelling of deep water, which supplies nutrients to the surface layer and leads to a marked increase in phytoplankton growth. Remotely sensed data on ocean color are used here to show that the resulting distribution of phytoplankton exerts a controlling influence on the seasonal evolution of sea surface temperature. This results in a corresponding modification of ocean-atmosphere heat exchange on regional and seasonal scales. It is shown that this biological mechanism may provide an important regulating influence on ocean-atmosphere interactions.

Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo.

Abstract: The adhesion receptors, LFA-1 and VLA-4, on lymphocytes mediate lymphocyte adherence to cytokine-activated endothelial cells (EC) in vitro. Based on our previous data, which suggested that the mAb TA-2 reacted with rat VLA-4, the effect of TA-2 on lymphocyte migration out of the blood was examined. Small peritoneal exudate lymphocytes (sPEL) preferentially migrate to cutaneous inflammatory reactions, whereas lymphocytes from peripheral lymph nodes (PLN) migrate poorly to inflammatory sites but home avidly to PLN. Treatment of sPEL with TA-2 inhibited sPEL migration to DTH, LPS, poly I:C, IFN-gamma, IFN-alpha/beta, and TNF-alpha by 35 to 65% and their accumulation in PLN by 50%. The homing of PLN lymphocytes to PLN was not inhibited by TA-2. Spleen T cell migration to cutaneous inflammatory sites was inhibited but homing to PLN was not affected. Systemic treatment with TA-2 inhibited sPEL migration to inflamed or cytokine-injected skin by up to 70%. Similarly, TA-2 strongly inhibited the migration of Ag-stimulated PLN lymphoblasts to skin and to PLN. The migration of lymphocytes from all sources, including the peritoneum, spleen, PLN, mesenteric nodes, and Peyer's patches, to mesenteric lymph nodes and Peyer's patches was inhibited by 80% and 95%, respectively. In conclusion, our results suggest that VLA-4 and possibly other alpha 4 integrins mediate the migration of the inflammation-seeking sPEL and Ag-activated lymphoblasts to cutaneous inflammatory sites and lymph nodes but do not affect the homing of PLN lymphocytes to PLN. These integrins also appear to be necessary for the migration of all types of lymphocytes to Peyer's patches and mesenteric lymph nodes.

Hypotheses to explain high-nutrient conditions in the open sea

Abstract: Ocean high-nutrient, low-chlorophyll waters are characterized principally by the persistence of major nutrients at the sea surface. This condition indicates control of autotrophic production by something other than NO{sub 3} or PO{sub 4}, but the nature of this control is at present unresolved. The range of hypotheses to explain the high-nutrient condition is illustrated by the grazing hypothesis (specific growth rates of phytoplankton are maximal and environmental stability allows development of a balanced food web that maintains low standing crops of phytoplankton) and the iron hypothesis (standing crop of plankton is constrained by availability of Fe: if more Fe were available, the standing crop of phytoplankton would increase and NO{sub 3} would be depleted, despite grazing). The iron hypothesis has been examined experimentally in the subarctic and equatorial Pacific and in Antarctic waters. In each environment, Fe enrichment enhanced the field yield of phytoplankton and that enrichment of high-nutrient waters with Fe would change the species composition of phytoplankton and food-web interactions, thereby enhancing utilization of NO{sub 3}. The magnitude of this enhancement cannot be predicted with confidence.

Cell counts and maps in the larval central nervous system of the ascidian Ciona intestinalis (L.).

Abstract: Although the ascidian tadpole larva harbors a prospectively valuable prototype of the chordate nervous system, with extensively characterized neural plate cell lineages, the simple cellular composition of the resultant central nervous system (CNS) is not documented in detail. The average total number of cells in the larval CNS of Ciona intestinalis is 335 (range ±4, n = 3), 65 or 66 of which reside in the nerve cord of the tail. The estimates were made by tracing and counting the number of nuclei in serial semithin (1 mm) sections cut longitudinally through three larvae, fixed no later than 2 hours after hatching. Within a single fourth larva, L4, 266 cells constituted the CNS in the trunk region of the larva, 45 of which occurred within the visceral ganglion, 215 in the sensory vesicle, and 6 in the neck between the two. Each cell was assigned to one of thirteen categories. Most (182, roughly 68%) are classified as ependymal, a specialized non-neural cell peculiar to embryonic and larval chordates, from their position lining the cavities of the neural tube's elaborations or from clear similarities in the cytological appearance to those that do. Five cells are accessory cells of the sensory structures: three lens cells and a pigment-cup cell in the ocellus, and a single pigment cell in the otolith. Of the remaining 79 cells, 36 are sensory, 17 receptors in the ocellus and 19 presumed hydrostatic pressure receptors; these lie on the right and left, sides of the sensory vesicle, respectively. Eighteen of the visceral ganglion cells have been tentatively classified as neurons, as have the remaining 25 cells which form two clusters in the posterior region of the sensory vesicle.

Estimation of new production in the ocean by compound remote sensing

Abstract: Compound remote sensing, a technique for estimating oceanic new production using remotely sensed data on ocean color and temperature, is discussed. This approach, which depends on parameterizations developed from ship observations as well as on satellite data, yields more representative estimates of the large-scale average new production than those calculated from ship data alone. The approach is illustated with data for the Georges Bank.

Role of coral reefs in global ocean production

Abstract: Coral reefs cover some 600 × 103 km−2 of the earth’s surface (017% of the ocean surface) First-order estimates show coral reefs to contribute about 085% of the estimated net CO2 fixation rate of the global oceans Gross CO2 fixation is relatively high (about 700 × 1012 gC yr−1), but most of this material is recycled within the reefs Excess (net) production of organic material (E) is much smaller, about 20 × 1012 gC yr−1 We estimate that 3 × 1012 gC yr−1 (15% of E) is buried in reef structure; 2 × 1012 gC yr−1 (10% of E) for sustained human harvest, and the remaining 75% of E for export from coral reefs to adjacent areas Comparison of estimates for net production by reefs and their surrounding oceans indicates that the excess production by coral reefs is similar to new production in the photic zone of the oligotrophic oceans Consequently, estimates for global ocean production should include as a first approximation areas of reefs with the surrounding ocean when assigning average net production rates While there are significant uncertainties in these numbers, we conclude that organic production by reefs plays a relatively minor role in the global scale fluxes and storage of elements In comparison, the companion process of biologically-mediated inorganic carbon precipitation represents a major role for reefs While reef production does respond on local scales to variation in ocean climate, neither the absolute rates nor the amount accumulated into organic pools are either sensitive indicators or accurate recorders of climatic change in most reef systems Similarly, the productivity of most reefs should be little affected by the environmental changes currently predicted from the Greenhouse Effect

Clinical and Biochemical Parameters of Androgen Action in Normal Healthy Caucasian Versus Chinese Subjects

Abstract: Stimulation of androgen-sensitive hair follicles is mediated by dihydrotestosterone (DHT), which is formed in these tissues by 5α-reduction of testosterone. A possible mechanism for increased body hair in some human populations might, therefore, be an increase in 5α-reductase activity, resulting in elevated tissue levels of DHT. If present, this finding could have other important clinical implications, since the 5α-reductase enzyme is pivotal in the pathophysiology of prostatic disease. To explore differences in clinical and biochemical parameters of androgen action, we conducted a study of 184 Caucasian and Chinese subjects in whom we evaluated chest hair density and serum levels of androgen precursors and 5α-reduced androgen metabolites. Differences in chest hair density were most notable in the men, in whom comparative mean chest hair scores (using a scale of 0-4) were 3.0 vs. 0.8 (P < 0.0001), Caucasian vs. Chinese. Levels of 5α-reduced androgen products were also strikingly higher in the Cau...

ACE inhibitor fetopathy and hypocalvaria: The kidney–skull connection

Abstract: Two cases of angiotensin converting enzyme inhibitor fetopathy with renal tubular dysgenesis and severely underdeveloped calvarial bone are described. Six additional, unexposed cases of hypocalvaria are described, and possible links between calvarial development and fetal hypotension and/or chronic hypoxia are explored.

Controlled Trial of a Home and Ambulatory Program for Asthmatic Children

Abstract: Care of asthmatic children is often episodic and more therapeutic than preventive. A 2-year randomized, controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures. Interventions for the study group during the first year included 3-month clinic visits, education, and home visits by a specially trained research nurse. Control subjects continued to receive regular care from a family physician or pediatrician. Eighty-nine subjects (93%) completed the study. Study subjects had less school absenteeism than control subjects (10.7 vs. 16.0 days, P = .04) and showed significantly better small airway function after 1 year. Asthma severity improved in 13 study subjects and worsened in 5. The reverse was true for control subjects. Study subjects exhibited better metered aerosol technique than control subjects (P = .0005). Fewer days were spent in hospital by the study subjects admitted compared with control subjects (3.67 vs 11.2 days, P = .02). After 1 year, more study than control families (72.1% vs 33.1%, P = .006) reported that their asthmatic child took responsibility for the asthma management. The intervention failed to reduce exposure to secondhand smoke or to household pets. There were no significant differences in medical visits, theophylline levels, or records of asthma symptoms. One year after discontinuing the intervention, a marked "washout" effect was observed. Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained.

Interactions between sea urchins (Strongylocentrotus droebachiensis) and their predators in field and laboratory experiments

Abstract: Field observations and manipulative experiments in a nearshore cobble bed (2 to 3 m below mean low water) at Eagle Head, Nova Scotia, Canada, between 1984 and 1986, showed that small juveniles ofStrongylocentrotus droebachiensis (3 to 6 mm diam) sheltering beneath cobbles had a refuge from predators such as rock crabs, small lobsters, and fish. Sea urchins gradually outgrew these refuges and small adults (25 to 30 mm) required larger rocks as shelter from predators, particularly large cancrid crabs. Small juveniles were usually solitary and well dispersed beneath cobbles, whereas small adults tended to aggregate on the undersides and in the interstices of boulders. These aggregations may develop passively as sea urchins accumulate in suitablysized refuges. Chemotaxis experiments indicate that juvenileS. droebachiensis are repelled by waterborne stimuli from conspecifics. In a factorial experiment, effects of the presence of potential predators (rock crabs and lobsters) and/or food (kelp) on the behaviour of large juvenile (10 to 15 mm) and small adult sea urchins were examined in flowing seawater tanks. Both size classes formed exposed feeding aggregations when kelp was provided as food, irrespective of the presence or absence of predators. In the absence of kelp, each size class responded differently to the presence of a predator: juveniles became more cryptic, whereas adults aggregated on the tank sides. Increased movement to the sides of a tank in the presence of a predator may reflect a flight response, since chemotaxis experiments indicated thatS. droebachiensis is repelled by waterborne chemical stimuli from predators. Observational and experimental data suggest that predation at the late juvenile and early adult stages may influence population structure, distribution and abundance ofS. droebachiensis.

Peer problems in Tourette's disorder.

Abstract: To explore the social adjustment and peer relationships of children with Tourette9s disorder, 29 patients with mild to moderate Tourette9s disorder were studied. Children underwent neuropsychological testing. The patients completed self-esteem scales and their parents and teachers completed behavior rating scales. Peer relationships were examined with the Pupil Evaluation Inventory, which is a sociometric questionnaire completed by the child9s classmates and provides measures of aggression, withdrawal, and likability. As a group, Tourette9s disorder patients were significantly more withdrawn, more aggressive, and less popular than their classmates. Thirty-five percent of the children with Tourette9s disorder received the lowest rating in the class on one or more of the Pupil Evaluation Inventory factors. These social problems were not predicted by the frequency or duration of tics. A clinical diagnosis of attention-deficit hyperactivity disorder and teachers9 ratings on the summary scale of the Child Behavior Checklist and the Pupil Evaluation Inventory did predict poor adjustment. It is concluded that social adjustment is a major difficulty for many children with Tourette9s disorder, irrespective of tic severity.

Social organization of female sperm whales and their offspring: constant companions and casual acquaintances

Abstract: Associations among female sperm whales, Physeter macrocephalus, and their dependent offspring, off the Galapagos Islands were studied between 1985 and 1989. The whales were found in groups containing about 23 individuals, with each individual having approximately 12 constant (over years) companions. These permanent units associated with one another for periods of ≅6.5 days, although the rate and duration of these associations seemed to vary between years, perhaps because of differences in the food supply. The principal function of the closed units may be care of the offspring, and units in the same general area may derive benefit from feeding in a coordinated manner.

Noonan-like/multiple giant cell lesion syndrome.

Abstract: A patient with the Noonan-like/multiple giant cell lesion syndrome is reported and the findings in 14 cases are reviewed. Impressive manifestations include short stature, low normal intelligence or developmental delay, ocular hypertelorism, prominent posteriorly angulated ears, giant cell lesions of bones, joints, and/or soft tissues, pectus excavatum, and pulmonic stenosis. It has been difficult to delineate the syndrome because problems in identifying the condition have resulted from incomplete or truncate ascertainment by various medical specialists.