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PubMed2025

A Digital Tool for Clinical Evidence-Driven Guideline Development by Studying Properties of Trial Eligible and Ineligible Populations: Development and Usability Study.

BACKGROUND: Clinical guideline development preferentially relies on evidence from randomized controlled trials (RCTs). RCTs are gold-standard methods to evaluate the efficacy of treatments with the highest internal validity but limited external validity, in the sense that their findings may not always be applicable to or generalizable to clinical populations or population characteristics. The external validity of RCTs for the clinical population is constrained by the lack of tailored epidemiological data analysis designed for this purpose due to data governance, consistency of disease or condition definitions, and reduplicated effort in analysis code. OBJECTIVE: This study aims to develop a digital tool that characterizes the overall population and differences between clinical trial eligible and ineligible populations from the clinical populations of a disease or condition regarding demography (eg, age, gender, ethnicity), comorbidity, coprescription, hospitalization, and mortality. Currently, the process is complex, onerous, and time-consuming, whereas a real-time tool may be used to rapidly inform a guideline developer's judgment about the applicability of evidence. METHODS: The National Institute for Health and Care Excellence-particularly the gout guideline development group-and the Scottish Intercollegiate Guidelines Network guideline developers were consulted to gather their requirements and evidential data needs when developing guidelines. An R Shiny (R Foundation for Statistical Computing) tool was designed and developed using electronic primary health care data linked with hospitalization and mortality data built upon an optimized data architecture. Disclosure control mechanisms were built into the tool to ensure data confidentiality. The tool was deployed within a Trusted Research Environment, allowing only trusted preapproved researchers to conduct analysis. RESULTS: The tool supports 128 chronic health conditions as index conditions and 161 conditions as comorbidities (33 in addition to the 128 index conditions). It enables 2 types of analyses via the graphic interface: overall population and stratified by user-defined eligibility criteria. The analyses produce an overview of statistical tables (eg, age, gender) of the index condition population and, within the overview groupings, produce details on, for example, electronic frailty index, comorbidities, and coprescriptions. The disclosure control mechanism is integral to the tool, limiting tabular counts to meet local governance needs. An exemplary result for gout as an index condition is presented to demonstrate the tool's functionality. Guideline developers from the National Institute for Health and Care Excellence and the Scottish Intercollegiate Guidelines Network provided positive feedback on the tool. CONCLUSIONS: The tool is a proof-of-concept, and the user feedback has demonstrated that this is a step toward computer-interpretable guideline development. Using the digital tool can potentially improve evidence-driven guideline development through the availability of real-world data in real time.

Humans↗

PubMedDate not supplied

General types of relationships between the development of the organism and the development of the subsystems of the organism.

There are elementary and complex types (combined elementary types): of temporospatial relations between the pattern of development of the organism and the patterns of development of individual subsystems; of influences exercised by the development of the organism upon the development of the subsystems of the organism; of influences exercised by the development of individual subsystems upon individual development; of temporospatial relations between the stability of the line of individual development and the stability of the line of development of individual subsystems; of mutual influence between the stability and variation of the line of individual development, on the one hand, and the stability and variation of the line of development of the individual subsystems, on the other.

Environment↗

PubMed1979

Golgi studies on Purkinje cell development in the frog during spontaneous metamorphosis. II. Details of dendritic development.

The development of Purkinje cell dendrites was studied in the bullfrog from premetamorphic tadpoles to 10-week-old postmetamorphic frog-lets by the Golgi-Kopsch method. In this species two distinct patterns of arbor formation may be seen, which appear to be related to differences in the timing of initial dendritic development. In Purkinje cells that begin development in early tadpole stages, the dendritic tree is elaborated by continuous and concomitant growth and branching, a process by which the developing arbor expands in both height and width. Arbor formation in Purkinje cells that begin development in metamorphosing tadpoles proceeds in two separate steps. Initially, dendrites of such cells elongate, but form only a few poorly developed branches; only when the arbor reaches near-adult height does branching become extensive. Additional differences present in Purkinje cells are reflected in the paucity of growth cones and filopodia in the tadpole, and numerous filopodia and growth cones in the metamorphic period. An interesting feature of dendritic development in this species is a tendency to alter the arboreal domain by the formation of extra-arboreal dendrites, and possibly by the occasional resorbtion of other partially formed dendrites. The pattern of dendritic development in the frog is different than in mammals and is difficult to interpret. Such unusual development may be due to disturbances in the timing of the formation of Purkinje cell dendrites and of the establishment of the external granular layer (EGL).

Animals↗

PubMed1978

Golgi studies on Purkinje cell development in the frog during spontaneous metamorphosis. I. General pattern of development.

The development of Purkinje cells was studied in the bullfrog from prometamorphic tadpoles to 10-week-old postmetamorphic froglets by the Golgi-Kopsch method. In this species, the rate of Purkinje cell development is unusually slow and proceeds in two waves. The first wave of development begins prior to the establishment of the external granular layer (EGL), and proceeds slowly for two to three months during the formation of the EGL; then accelerating as metamorphosis is being completed, the cells reach near-adult dimensions a month later. Even prior to the formation of the EGL these cells are already present in the stage of dendritic orientation and flattening which, however, varies from the norm. The second wave of Purkinje cell development begins during metamorphosis and proceeds at a more rapid pace until two months after metamorphosis, at which time they appear to have reached adult dimensions. In these cells the development of the apical dendrite does not always coincide with the stellate stage but may proceed directly to the stage of dendritic orientation and flattening which, in accordance with the norm, is towards the pia and in the sagittal plane. Many variations are present in the dendritic trees and orientation of the dendritic branches of Purkinje cells throughout their development. These variations are similar to those seen in mammals, however, since the frog cerebellum consists of a simple plate, they cannot be attributed to a Cartesian transformation of dendrites to accomodate the curvatures of a folial pattern. Similarly, since these morphological variations occur in the course of normal development they cannot be attributed to a reaction to, or recovery from, injury during development.

Animals↗

PubMed1991

Development of the olfactory nerve in the African clawed frog, Xenopus laevis: I. Normal development.

Quantitative and morphological data were obtained on developing olfactory axons in the African clawed frog, Xenopus laevis, during late premetamorphosis (stages 48-54), prometamorphosis (stages 55-57), and halfway through metamorphic climax (stages 58-62). Larval axons throughout these stages of development did not change with respect to morphology or diameter and were similar in all respects to olfactory axons described in other vertebrate species. The number of axons in the olfactory nerve increased throughout development, more rapidly after stage 54. Based on comparisons of the number of axons in proximal and distal regions of the nerve, there also appeared to be more axons growing into the olfactory nerve at early metamorphic climax than during premetamorphosis. Through the onset of metamorphic climax, the number of olfactory axons was correlated with other measures of body growth. In the later stages of climax, however, the number of olfactory axons continued to rise, whereas body weight, length, and width, as well as olfactory nerve length, decreased. Not all animals developed at the same rate, but for all quantitative measurements in this study, stage was a better predictor of any given parameter than age of the animal. Rearing conditions affected the rate of development but did not have a significant effect on most of the features analyzed quantitatively. Although most of the new olfactory axons in these larval animals probably represent addition of fibers resulting from development, the ensheathing glial cells at all stages showed evidence of phagocytic activity, suggesting that there might be turnover of olfactory receptor cells during larval development. The results presented here provide a baseline for future reports on various factors that may influence normal development in this system.

Animals↗

PubMed1978

[Light microscopic studies on the development of Theileria annulata (Dschunkowsky and Luhs, 1904) in Hyalomma anatolicum excavatum (Koch, 1844). II. The development in haemolymph and salivary glands (author's transl)].

Fully differentiated kinetes, average length 17.6 micrometer, appeared in the haemolymph of engorged nymphs usually 17 to 20 days after repletion. Kinetes were observed at first in the salivary glands on day 18 after repletion. The kinetes then transformed into fission bodies of about 10 micrometer in diameter, mainly in type III alveoli and less frequently in type II alveoli. The fission bodies grew up to a size of about 20 micrometer after several divisions of their nucleus. At this time the ticks moulted and no further development occurred until activation. Shortly before infestation the salivary glands began to proliferate, and rapid growth of the fission bodies was observed, especially in young ticks where development of 'infective particles' ('sporozoites') was concluded within two days. Development in feeding adult ticks apparently occurred in four major steps: (1) Division of primary fission bodies (sporonts) into numerous secondary fission bodies ('primary sporoblasts'), (2) division of secondary fission bodies into tertiary fission bodies ('secondary sporoblasts'), (3) production of particles ('sporozoites') by tertiary fission bodies and release of particles into the saliva, and (4) degeneration of fission bodies and their host cell but further release of particles. The host cell was stimulated to giant growth, thus its diameter increased, on average, from 15 to 110 micrometer. Heavy infections resulting from parasitaemias of greater than 40% caused disease and mortality in the tick population. Development was much retarded by aging. In ticks starved for six months 'sporozoites' did not develop before day five to seven of infestation. 'Sporozoites' did not develop before day five to seven of infestation. 'Sporozoites' may not develop at all in six to nine month old female ticks during the infestation period. The significance of the described developmental stages of T. annulata was discussed and a sexual generation postualted. The hypothetic development of T. annulata in its tick vector was illustrated.

Animals↗

PubMed1990

Influence of different developing solutions and developing times on radiographic caries diagnosis.

One hundred extracted premolars were radiographed under standardized conditions with D- and E-speed films. The films were developed with conventional and rapid processors using varying developing times. The influence of different developers and developing times on the diagnostic accuracy of radiographic caries diagnosis was evaluated with the aid of ROC technique. Rapid processing using the developing time recommended by the manufacturer led to a lower density and contrast compared with the conventional developer. Underdeveloped films using the rapid processors resulted in an unacceptable low level of diagnostic accuracy, but otherwise it was the same for all developers, developing times and both types of film.

Bicuspid↗

PubMed1991

Patients who develop postanesthesia shaking show no difference in postoperative temperature from those who do not develop shaking.

While the cause of postanesthesia shaking (PS) remains unknown, nurses traditionally believe that the etiology of PS is hypothermia. Two theoretical constructs have been proposed to describe the development of PS. The first is based on classic thermoregulation theory. The second is based on spinal reflex hyperactivity. The purpose of this comparison study was to determine if significant differences in postoperative temperature, as well as change in preoperative to postoperative temperature, exists between patients who develop and who do not develop PS. The study also examined the difference in postoperative temperature between women and men. Postoperative axillary temperature was measured on admission to the PACU. The nonprobability convenience sample consisted of patients between the ages of 18 and 89 years who were extubated and breathing spontaneously following general anesthesia. PS developed in 120 of 533 patients. By t-test analysis, there was no statistical significant difference between groups in postoperative mean temperature (P greater than .10) or in preoperative to postoperative mean temperature change (P greater than .40). The group that developed PS had a narrower and higher range of postoperative temperature and a smaller preoperative to postoperative temperature change than those who did not develop PS. In both groups, 52% of the patients were hypothermic (less than 35 degrees C[less than 95 degrees F]) on PACU admission. Women had lower postoperative mean temperature than men (P less than .05). Findings indicate that temperature on PACU admission is not a variable of difference between groups of patients who develop or who do not develop PS. As postoperative temperature decreases, the incidence of PS does not increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

The Minnesota Child Development Inventory: validity and reliability for assessing development in infancy.

The concurrent validity and reliability of the Minnesota Child Development Inventory (MCDI) was assessed by comparing the MCDI general development index score, and each of the seven subscale scores, with the mental and psychomotor age equivalents achieved on the Bayley Scales of Infant Development. In addition, the co-positivity, co-negativity, positive and negative predictive values of the MCDI in identifying infants with a mental development index (MDI), or psychomotor development index (PDI) of greater than 2 SD below the mean were assessed. Subjects were 101 infants (8 to 19 months old) who were seen at a neonatal developmental follow-up clinic after discharge from the neonatal intensive care unit. Correlations were obtained for the entire sample as well as for the two chronological age groups (i.e., 8 to 10 months and 17 to 19 months) within the sample. A strong correlation between the MCDI scales and the Bayley Mental and Psychomotor Scales was documented for the entire population as well as for the individual age groups. The overall validity of the MCDI in identifying infants with a MDI or PDI of greater than 2 SD below the mean was limited due to relatively poor co-positivity and positive predictive value. Although the MCDI may yield consistent information about the development of an infant's skills, this research suggests the MCDI has limited capacity to discern infants having delayed development.

Aptitude↗

PubMed1991

Development and DNA polymerase activities in cultured preimplantation mouse embryos: comparison with embryos developed in vivo.

Embryos from superovulated female mice that developed in vitro from the two-cell stage were compared with in vivo embryos with respect to yield of blastocytes, number and types of cells, morphology in histologic section, and DNA polymerase activities. Significantly more embryos developed into blastocytes in vitro (93%) than in vivo (18%). Inner cell mass (ICM) cells comprised approximately 30% of total cells in late morula/early blastocyst stage embryos developed either in vitro or in vivo. However, the in vitro embryos developed approximately half the number of total cells as in vivo embryos, did not develop endoderm, and did not develop abembryonic trophoblast cells with morphologic characteristics of late preimplantation in vivo embryos. DNA-dependent DNA polymerase activities in in vitro embryos decreased in correspondence with the decrease in cell number resulting in per cell levels comparable to in vivo embryos. In contrast, the poly (A).oligo(dT)-dependent DNA polymerase activity was the same in embryos developing either in vitro or in vivo, indicating different regulatory mechanisms for the two enzyme activities. A variety of nutrients and growth factors in the culture medium did not increase cell numbers or DNA polymerase activities in embryos cultured for 3 days; extending the culture an additional 24 hours resulted in a loss of ICM cells and decreases in both DNA polymerase activities. These results show that the retarded growth of embryos in vitro is equally distributed between ICM and trophoblast, is not reversed by culture conditions that include serum growth factors, and is not due to decreased cellular levels of DNA polymerase activities.

Animals↗

PubMed1991

The development of traffic and traffic safety in six developed countries.

Two models are presented, describing the development of traffic and traffic safety. Traffic volumes, measured by the total amount of vehicle kilometers per year, are expected to follow a sigmoid saturation curve over time. The logistic function is used to model this development. The fatality rate, the number of fatalities per vehicle kilometer, is chosen to measure safety. The (negative) exponential function is selected to model the fatality rates over time. It is argued that these two aspects of the traffic system are fundamental and that the development of the number of fatalities results by multiplication. Given this assumption, the fall in the number of fatalities, noticed in almost all developed countries after a steady increase until 1970, does not need a special explanation. It follows from the combination of the monotonically increasing traffic volumes and the monotonically decreasing fatality rates. The two parsimonious models fit the data fairly well for six developed countries. The parameters differ substantially between countries, but also show common features. It is found from the parameters of the logistic function, that for all countries the points of maximum increase in traffic volume coincide just after 1970, the moment of the energy crisis. It is concluded from this finding that the energy crisis was caused by the cumulating demands of the oil-consuming countries, resulting in a reaction of the oil-producing countries. From the parameters of the exponential function, it is found that there also is a common point of intersection for fatality rates around 1980. It is shown that the development of safety is directly related to the development of traffic. The ten-year delay is interpreted as the time necessary for planning and implementation of safety measures. Finally, a striking relation is found between the volume parameters and the fatality-rate parameters, suggesting that the number of fatalities is a function of the derivative of the amount of traffic in the mathematical sense.

Accidents, Traffic↗

PubMed1991

Development and growth of mouse embryonic kidney in organ culture and modulation of development by soluble growth factor.

Differentiation of the metanephrogenic mesenchyme is triggered by an inductive tissue interaction between an inducer tissue and the mesenchyme. It is generally believed that the epithelial ureter bud acts as an inducer during in vivo development. In response to the inductive stimulus most of the mesenchymal cells convert into epithelial cells, while a small fraction differentiates into stromal cells. In vitro, differentiation of isolated mesenchyme to epithelium can be induced by a variety of embryonic tissues, but nothing is known about the molecular nature of the inducing stimulus. In recent years, large numbers of polypeptide growth factors have been described, which in addition to proliferative effects were shown to exert effects on a variety of biological phenomena such as chemotaxis, inflammation, tissue repair, or induction of embryonic development. We therefore analyzed whether growth factors in the absence of inducer tissue can induce isolated kidney mesenchyme to differentiate into epithelium or interstitium. As expected, both growth and differentiation into epithelium were stimulated by an inducer tissue, the spinal cord. We found that none of the various growth factors tested (including epidermal growth factor, transforming growth factors alpha and beta, insulin-like growth factors I and II, fibroblast growth factor, platelet-derived growth factor, and retinoic acid) could mimick the effect of an inducer tissue, although we tested the factors over a wide concentration range. One of the tested factors, epidermal growth factor (EGF) stimulated the mesenchymal cells to become stromal cells, although it could not stimulate development into epithelium. EGF could stimulate stromal development both when the mesenchyme was cultured in isolation and when the mesenchyme was stimulated by an inducer tissue to become epithelium. The expansion of the stromal compartment in response to EGF treatment occurred at the expense of the epithelial cells, but EGF could not completely suppress the formation of epithelium. These data suggest the presence of EGF receptors in the developing kidney, but since application of soluble EGF leads to abnormal development, soluble EGF cannot be the natural ligand. We suggest that locally produced mitogens with an EGF-like structure may regulate the relative amounts of stroma (interstitium) and epithelium in the developing kidney.

Animals↗

PubMed1991

The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries.

A hospital-based case-control study was conducted in eight developing and three developed countries to determine whether use of combined oral contraceptives alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of oral contraceptives, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing than developed countries. Both causal and non-causal interpretations of this finding have been offered. No associations were found between oral contraceptives and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas; but the power of this study to detect alterations in risks of these neoplasms in long-term users was low.

Breast Neoplasms↗

PubMed1992

Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. III. An immunohistochemical analysis of the distribution of the neural tissue antigen G1N2 in the embryonic heart; implications for the development of the atrioventricular conduction system.

A monoclonal antibody raised against an extract from the Ganglion Nodosum of the chick and designated G1N2 proves to bind specifically to a subpopulation of cardiomyocytes in the embryonic human heart. In the youngest stage examined (Carnegie stage 14, i.e., 4 1/2 weeks of development) these G1N2-expressing cells are localized in the myocardium that surrounds the foramen between the embryonic left and right ventricle. In the lesser curvature of the cardiac loop this "primary" ring occupies the lower part of the wall of the atrioventricular canal. During subsequent development, G1N2-expressing cells continue to identify the entrance to the right ventricle, but the shape of the ring changes as a result of the tissue remodelling that underlies cardiac septation. During the initial phases of this process the staining remains recognizable as a continuous band of cells in the myocardium that surrounds the developing right portion of the atrioventricular canal, subendocardially in the developing interventricular septum and around the junction of the embryonic left ventricle with the subaortic portion of the outflow tract. During the later stages of cardiac septation, the latter part of the ring discontinues to express G1N2, while upon the completion of septation, no G1N2-expressing cardiomyocytes can be detected anymore. The topographic distribution pattern of G1N suggests that the definitive ventricular conduction system derives from a ring of cells that initially surrounds the "primary" interventricular foramen. The results indicate that the atrioventricular bundle and bundle branches develop from G1N2-expressing myocytes in the interventricular septum, while the "compact" atrioventricular node develops at the junction of the band of G1N2-positive cells in the right atrioventricular junction (the right atrioventricular ring bundle) and the ("penetrating") atrioventricular bundle. A "dead-end tract" represents remnants of conductive tissue in the anterior part of the top of the interventricular septum. The location of the various components of the avian conduction system is topographically homologous with that of the G1N2-ring in the human embryonic heart, indicating a phylogenetically conserved origin of the conduction system in vertebrates.

Antigens↗

PubMed1992

Direct-developing sea urchins and the evolutionary reorganization of early development.

The evolution of development can be made accessible to study by exploiting closely related species that exhibit distinct ontogenies. The direct-developing sea urchin Heliocidaris erythrogramma is closely related to indirect-developing sea urchins that develop via a feeding larval stage. Superficial consideration would suggest that simple heterochronies resulting in loss of larval features and acceleration of adult features could explain the substitution of direct for indirect development. However, our experiments show that early development has in fact been extensively remodeled, with modified localization of maternal determinants coupled with dissociation of cell cleavage from axis formation resulting in novel patterns of cell lineage differentiation and fate map. Gene expression has undergone concomitant changes.

Animals↗

PubMed1991

Development of resistance to coccidiosis in the absence of merogonic development using X-irradiated Eimeria acervulina oocysts.

Sporulated oocysts of the protozoan Eimeria acervulina were subjected to 0, 10, 15, 20, or 30 krad of X-irradiation and inoculated into susceptible outbred chickens to determine if radioattenuated coccidia could induce protection against parasite challenge. Irradiation treatment had an appreciable dose-dependent effect on parasite development. Insignificant numbers of oocysts were produced by chickens inoculated with parasites that had been exposed to greater than 10 krad X-irradiation. Sporozoites exposed to 15 or 20 krad irradiation conferred significant protection against the appearance of intestinal lesions after parasite challenge. Sporozoites subjected to the highest dose level (30 krad) did not produce any significant level of protection. To investigate this phenomenon further and assess intracellular parasite development, susceptible outbred strains of chickens were administered either nonirradiated (0 krad) oocysts or oocysts that were exposed to an optimal dose (15 krad) or a high dose (30 krad) of X-irradiation. Immunofluorescence staining of tissue sections from each treatment group at various intervals after the initial administration of irradiated parasites indicated that sporozoites exposed to 15 krad irradiation were as capable of invading the host intestinal epithelium as nonirradiated sporozoites. However, at 48, 60, 72, and 96 hr, there was a marked reduction in merogonic development in groups receiving irradiated sporozoites compared to those inoculated with nonirradiated parasites. The latter parasites underwent profuse merogonic development; in contrast, irradiated parasites demonstrated little (15 krad) or no (30 krad) merogonic development. These results suggest that induction of a protective immune response occurs during a critical period early in intracellular development of E. acervulina.

Animals↗

PubMed1991

Relationship between IgG1 and IgG4 antibodies to foods and the development of IgE antibodies to inhalant allergens. II. Increased levels of IgG antibodies to foods in children who subsequently develop IgE antibodies to inhalant allergens.

In the present investigation we have tested the hypothesis that children with a high IgG antibody response to foods have an increased risk of developing IgE antibodies to inhalant allergens. Sera from 106 children with an increased risk of developing IgE-mediated allergy were analysed. During the follow-up, in 54 of these children IgE antibodies to inhalant allergens appeared. A positive/negative IgG1 and IgG4 anti-food score was determined as described previously: sera from age-clustered unselected children were tested for the levels of IgG1 and IgG4 antibodies to common foods. For each IgG RAST and each age group, the 75-percentile was chosen as cut-off value. Each antibody level was thus converted into a positive (higher than the 75-percentile of the age group) or negative value. The number of positive tests was used as the score. High-risk children with a high IgG1 anti-food score more often developed inhalant-specific IgE antibodies than high-risk children with low IgG1 titres: 50% of the children with a high IgG1 anti-food score developed IgE antibodies to grass pollen. Fifty per cent of the children with a high and 14% of the children with a low IgG1 anti-food score developed IgE antibodies to cat dander. For the prediction of the development of IgE anti-mite (house dust mite), the IgG4 anti-food scores appeared less useful than the IgG1 anti-food scores; 46% of the IgG4 high responders versus 22% of the IgG4 low responders acquired IgE anti-mite, whereas for IgG1 these percentages were 73 and 19, respectively.

Allergens↗

PubMed1976

The effects of experimental unilateral anotia on skull development in the chick embryo. III. Chondrocranial development in anotic embryos of 7-20 days of incubation.

The study of the development of of the chondrocranium in chick embryos with unilateral (right-sided) anotia revealed the following main characteristics. 1. The median axes of the chordal and the prechordal part of the cranial base are not in a straight line but show a deviation toward the right side. The angle between the two axes has its vertex in the region of the foramen hypophyseos. 2. The metotic cartilage and the foramina of the IXth and Xth cranial nerves are normal in position. 3. The tectum synoticum develops later and to a lesser extent than normal. 4. Between the basal plate, the metotic cartilage, the occipital arch and the supracapsular cartilage a foramen is formed which, later in development, is closed by outgrowths of the metotic cartilage and the basal plate. 5. The "optic area" shows a practically normal appearance which indicates that the cartilaginous ventral wall of the lagenal capsule is of basal plate origin. 6. The pro-otic process develops practically normal and, hence, is independent of the ear capsule. 7. The quadrate cartilage and the right lower jaw are displaced ventro-posteriorward. The earliest development of the perichondral bones shows some particularities which are closely correlated with the development of the various cartilaginous structures.

Animals↗