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[Aging and normal physical values].

The physical features of healthy persons demonstrate considerable modifications in the range of the potential for extragenetic adaptation. The functional capacity is not identical in the total spectrum of adaptation; under the aspect of a wide adaptive scope physiological findings must also be evaluated against the background of normality. A minimal norm, a norm of the majority, an ideal norm and a special norm can be confirmed. The minimal norm is the border between physiology and pathology. The norm of the majority is the average of the healthy population. The ideal norm is characterized by an optimum of functional efficiency. The special norm is a prerequisite for special physical activities and high performances. The concept of normality as dependent on exercise-induced adaptation is relatively well established for persons in the so-called age of highest physical performance capacity. In this presentation the attempt is made to transfer the afore-mentioned concept of normality to the situation in later periods of life. The body is lifelong adaptable, but the position of the four categories of norms changes in the course of life. An efficient classification of norms based on exercise-induced adaptations is for older individuals of particular importance as these persons are at present to a high degree affected by hypokinesia with a subsequent maladaptation (atrophy).

Adaptation, Physiological↗

The ecology of Bulinus truncatus and Biomphalaria alexandrina and its implications for the control of bilharziasis in the Egypt-49 project area.

The respective vectors of the two forms of bilharziasis in Egypt do not have the same ecological distribution. Bulinus truncatus is most abundant in large canals, and decreases in density as the water approaches and flows into drains. Biomphalaria alexandrina is most abundant in drains, and decreases in density upstream from these habitats. Both species are most abundant in the presence of aquatic vegetation, but they differ in their respective associations with the water hyacinth, Eichhornia crassipes. Biomph. alexandrina reaches maximum abundance in the presence of this plant, but Bul. truncatus is as uncommon in the absence of plants as in the presence of E. crassipes.Calculation of life-table parameters from field data shows that, under optimum field conditions, both species can double their populations in 14-16 days. The reproductive rates of both species are greatest in March and the death rates in midsummer. The observed peak densities in May and June give a false impression of optima because of undercollection of young snails, which are most abundant in March and April.Control operations should take advantage of the findings on population parameters. A single area-wide treatment with molluscicide in April is recommended. During the remainder of the year, search for isolated foci of snail breeding and individual treatment of these will effect large savings of chemical and will be effective in controlling the transmission of the parasites.

Animals↗

Spatio-temporal interaction in neurones of the cat's dorsal lateral geniculate nucleus.

Temporal contrast sensitivities in the range 0.33-42 Hz for optimum spatial frequency grating stimuli were measured for large populations of XG and YG neurones. For fewer cells, complete spatial contrast sensitivity profiles were measured at a series of temporal frequencies and, in some cases, at a range of levels of retinal illumination too. Contrast sensitivities were measured from responses of cells reliably different from their maintained discharges. The cells' discharges were recorded extracellularly from the binocular segment of the A laminae of the cat's dorsal lateral geniculate nucleus. At their respective optimum spatial frequencies, YG cell were more sensitive on average than XG cells for most temporal frequencies, though the average temporal contrast sensitivity profiles of both cell classes had similar shapes. The optimum temporal frequency for both cell types was around 5 Hz. XG and YG cells seem to be relatively less sensitive to low temporal frequencies than their ganglion cell counterparts. At a retinal illumination of 230 cd/m2 (pupil, 3 mm2), increasing temporal frequency in the range 0.65-21 Hz produced a relative improvement in low spatial frequency contrast sensitivity in most XG and all YG cells studied. There were some XG cells, though, which showed little or no effect of temporal frequency on their spatial contrast sensitivity curves. At all temporal frequencies, the shapes of spatial contrast sensitivity curves and the cells' temporal contrast sensitivity profiles were not markedly dependent on the criterion level set to measure 'threshold' contrast. Reducing the level of retinal illumination in the range 230-0.007 cd/m2 (pupil, 3 mm2) produced a fall in contrast sensitivities for both XG and YG cells. The loss in sensitivity was more marked at high spatial and high temporal frequencies. The similar shapes of the temporal contrast sensitivity curves of XG and YG cells weakens the suggestion that the human counterparts of these cells would provide a suitable physiological substrate for the psychophysical sustained and transient channels. Although the behaviour of XG and YG cells parallels quite closely changes in cat and human psychophysical spatial contrast sensitivities with temporal frequency and retinal illumination, many problems remain for equating results from the two fields.

Animals↗

Sexual dimorphism in relation to current selection in the house finch.

Sexual dimorphism is thought to have evolved in response to selection pressures that differ between males and females. Our aim in this study was to determine the role of current net selection in shaping and maintaining contemporary sexual dimorphism in a recently established population of the house finch (Carpodacus mexicanus) in Montana. We found strong differences between sexes in direction of selection on sexually dimorphic traits, significant heritabilities of these traits, and a close congruence between current selection and observed sexual dimorphism in Montana house finches. Strong directional selection on sexually dimorphic traits and similar intensities of selection in each sex suggested that sexual dimorphism arises from adaptive responses in males and females, with both sexes being far from their local fitness optimum. This pattern is expected when a recently established population experiences continuous immigration from ecologically distinct areas of a species range or as a result of widely fluctuating selection pressures, as found in our study. Strong and sexually dimorphic selection pressures on heritable morphological traits, in combination with low phenotypic and genetic covariation among these traits during growth, may have accounted for close congruence between current selection and observed sexual dimorphism in the house finch. This conclusion is consistent with the profound adaptive population divergence in sexual dimorphism that accompanied very successful colonization of most of the North America by the house finch over the last 50 years.

Adaptation, Physiological↗

Relating vernier acuity and Snellen acuity in specific clinical populations.

The relationship between vernier acuity and Snellen acuity in a group of cataract patients was examined. The vernier stimulus consisted of two small spots of light, vertically separated by a variable-sized gap. The Snellen stimulus was a standard projected Snellen chart. The form of the relation between vernier and Snellen acuity was found to depend upon the vernier gap size used. Specifically, when the smaller gaps of 4 or 8 min of arc are used, the two types of acuity are linearly related. When the gap is 16 or 32 min of arc, (or if best vernier performance irrespective of gap is considered) vernier acuity is related to Snellen acuity by a power function with an exponent less than one, within this clinical population. Thus, with increasing degrees of retinal image degradation caused by cataract, optimum vernier acuity is impaired at a slower rate than Snellen acuity. Our results in cataract patients are compared to results obtained by others within a population of strabismic and anisometropic amblyopes.

Aged↗

Characteristics of the vegetative growth of Bacillus popilliae.

Growth characteristics of the insect pathogen, Bacillus popilliae Dutky, were studied by propagation in shaken flasks and in 2-liter fermentors. Maximal populations between 5 x 10(8) and 2 x 10(9) viable cells per milliliter of culture medium routinely were obtained in incubation periods of 18 to 24 hr at 30 C in a medium composed of 1.5% yeast extract, 0.6% K(2)HPO(4), and 0.2% glucose or trehalose. The carbohydrate required for growth in liquid media was fermented with the formation of 2 meq of acid per mmole of carbohydrate utilized; acid products ordinarily were not subsequently metabolized. B. popilliae is an aerobe, and the amount of growth obtained varied with aeration to an optimum at oxygen absorption rates of about 0.5. Maximal populations persist in a culture for periods of only 1 to 4 hr; cessation of growth was followed immediately by rapid death of cultures, so that less than 1% of the cells remained viable after 48 hr, and viability often was lost entirely by the end of 72 hr of incubation. No cytological evidence for spore formation was observed under any growth condition. Death was not associated with lysis of the cells, although extensive granulation ultimately occurred. Continuous neutralizaiton, augmented buffering, various techniques of dialysis, or slow feeding of the carbohydrate did not markedly alleviate the characteristic death of the cultures.

Acids↗

Towards a theory of evolutionary adaptation.

Most theoretical models in population genetics fail to deal in a realistic manner with the process of mutation. They are consequently not informative about the central evolutionary problem of the origin, progression, and limit of adaptation. Here we present an explicit distribution of phenotypes expected in an ensemble of populations under a mutation-selection-drift model that allows mutations with a distribution of adaptive values to occur randomly in time. The model of mutation is a geometrical model in which the effect of a new mutation is determined by a random angle in n dimensional space and in which the adaptive value (fitness) of an organism decreases as the square of the deviation of its phenotype from an optimum. Each new mutation is subjected to random genetic drift and fixed or lost according to its selective value and the effective population number. Time is measured in number of fixation events, so that, at any point in time, each population is regarded as genetically homogeneous. In this mutation-selection-drift model, among an ensemble of populations, the equilibrium average phenotype coincides with the optimum because the distribution of positive and negative deviations from the optimum is symmetrical. However, at equilibrium the mean of the absolute value of the deviation from the optimum equals square root of n-/8Ns), where n is the dimensionality of the trait space, N is the effective population size, and s is the selection coefficient against a mutation whose phenotype deviates by one unit from the optimum. Furthermore, at equilibrium, the average fitness across the ensemble of populations equals 1 - (n + 1)/8N. When n is sufficiently large, there is a strong mutation pressure toward the fixation of slightly deleterious mutations. This feature relates our model to the nearly neutral theory of molecular evolution.

Adaptation, Physiological↗

Development of a flow cytometry assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell-mediated hypersensitivity responses.

These studies were conducted to investigate the potential use of a flow cytometric analysis method for the identification and differentiation of chemicals with the capacity to induce irritation, IgE- or T cell-mediated hypersensitivity responses. An initial study investigated the ability of equally sensitizing concentrations (determined by local lymph node assay) of IgE-mediated (Toluene Diisocyanate-TDI) and T cell-mediated (Dinitrofluorobenzene-DNFB) allergens to differentially modulate the IgE+B220+ population in the lymph nodes draining the dermal exposure site. Sodium lauryl sulfate (SLS) was also tested as a nonsensitizing irritant control. Female B6C3F1 mice were dermally exposed once daily for 4 consecutive days, with the optimum time point for analysis determined by examining the IgE+B220+ population 8, 10, and 12 days post-initial chemical exposure. At the peak time point, day 10, the IgE+B220+ population was significantly elevated in TDI (41%), while moderately elevated in DNFB (18%) exposed animals when compared to the vehicle (0.8%), and remained unchanged in SLS (2.2%) exposed animals when compared to the ethanol control (2.5%). Experiments in our laboratory and others have demonstrated that the draining lymph node B220+ population becomes significantly elevated following exposure to allergens (IgE- and T cell-mediated), not irritants, allowing for their differentiation. An existing mouse ear swelling assay was used to identify chemical irritants. Therefore, using the endpoints of percent ear swelling, percent B220+ cells, and percent IgE+B220+ cells, a combined irritancy/phenotypic analysis assay was developed and tested with tetradecane (irritant), toluene diisocyanate, trimellitic anhydride (IgE-mediated allergens), benzalkonium chloride, dinitrofluorobenzene, oxazolone, and dinitrochlorobenzene (T cell-mediated allergens) over a range of concentrations. Based upon the pattern of response observed, a paradigm was developed for continued evaluation: Irritant exposure will result in significant ear swelling without altering the B220+ or IgE+B220+ populations. Exposure to sensitizers (IgE-mediated or T cell-mediated) will increase the B220+ population and the percent ear swelling will remain unchanged or will significantly increase, depending on the irritancy capacity of the chemical. Both the IgE+B220+ and B220+ populations will become elevated at the same test concentration following exposure to IgE-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will be equal to the percent of B220+ cells. The B220+ population will increase at a lower test concentration than the IgE+B220+ population, following exposure to T cell-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will reach less than half that of the percent of B220+ cells. The irritancy/phenotypic analysis method may represent a single murine assay able to identify and differentiate chemicals with the capacity to induce irritation, or IgE-mediated or T cell-mediated responses.

Administration, Cutaneous↗

Genetic algorithms and evolution.

The genetic algorithm (GA) as developed by Holland (1975, Adaptation in Natural and Artificial Systems. Ann Arbor: University of Michigan Press) is an optimization technique based on natural selection. We use a modified version of this technique to investigate which aspects of natural selection make it an efficient search procedure. Our main modification to Holland's GA is the subdividing of the population into semi-isolated demes. We consider two examples. One is a fitness landscape with many local optima. The other is a model of singing in birds that has been previously analysed using dynamic programming. Both examples have epistatic interactions. In the first example we show that the GA can find the global optimum and that its success is improved by subdividing the population. In the second example we show that GAs can evolve to the optimal policy found by dynamic programming.

Algorithms↗

Reduction of trend errors in power calculation by linear transformation of measured axial lengths.

PURPOSE: To find a method to improve the refractive outcome in short eyes and long eyes without sacrificing the outcome in normal eyes. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS: In a prospective study, 148 patients eligible for cataract surgery were measured with 2 different A-scans (BVI Axis, B.V. International; Sonomed 1500, Sonomed Inc.). Refraction was determined 6 weeks postoperatively. The postoperative refraction was compared with the refraction predicted by the Holladay 1, Hoffer Q, and SRK/T formulas; formula constants were optimized to give a zero mean error. The mean absolute error (MAE) was used as an outcome measure. RESULTS: The BVI Axis measured consistently shorter than Sonomed 1500. The mean axial lengths (ALs) were 23.033 mm and 23.435 mm, respectively. With the BVI Axis, an MAE of 0.44 diopter (D), 0.44 D, and 0.47 D was obtained, with the Holladay 1, Hoffer Q, and SRK/T formulas, respectively, with a trend toward undercorrecting short eyes and overcorrecting long eyes. The MAE with the Sonomed 1500 was 0.38 D, 0.39 D, and 0.40 D, respectively. By adding 0.402 mm to each measured value in the BVI Axis data set, the mean AL was transformed to 23.435 mm. With the transformed data, the MAE improved to 0.42 D, 0.43 D, and 0.44 D, respectively, with a reduced trend toward undercorrection and overcorrection. The 0.04 D difference between the instruments, although not statistically significant, may depend on measurement precision. Extending the concept of transformation, a minimum MAE of 0.41 D was obtained with the Holladay 1 at a mean AL of 24.0 mm, 0.43 D with Hoffer Q at 23.9 mm, and 0.40 D with SRK/T at 24.4 mm. The trend toward undercorrection and overcorrection was eliminated at the optimum for each formula. CONCLUSIONS: There were systematic differences in measured AL depending on equipment. Thus, the calculated powers differed and caused error in the degree of compliance between the labeled formula constant of an intraocular lens and the equipment used. Although personalization of formula constants reduces the mean error, in general a trend toward undercorrection of short eyes and overcorrection of long eyes will persist. Transforming the AL scale can eliminate the trend error and improve the overall refractive outcome. Transformation to a population mean AL of about 24.0 mm was close to optimum for the 3 formulas.

Cataract↗

Duration of patency of laser-assisted tympanic membrane fenestration.

BACKGROUND: Laser-assisted tympanic membrane fenestration (LTMF) provides intermediate-duration middle ear ventilation, which benefits selected children with acute otitis media (AOM) and otitis media with effusion (OME). OBJECTIVE: To evaluate clinical and technical factors that may affect duration of LTMF patency. DESIGN: Prospective clinical cohort effectiveness trial. SETTING: Four tertiary care children's hospitals. PATIENTS: Volunteer sample of 251 children (430 ears) followed up at 1, 2, 3, 4, 8, and 12 weeks; time to fenestration closure was evaluable in 201 ears, and assessment of cure at study conclusion was evaluable in 128 ears. INTERVENTIONS: Laser-assisted tympanic membrane fenestration for prospectively defined AOM or OME. The surgeon determined spot size, wattage, and concurrent adenoidectomy based on clinical judgment. MAIN OUTCOME MEASURES: Cure of AOM/OME with effusion at 90 days and duration of LTMF patency relative to spot size (1.8-2.8 mm), fenestration location on tympanic membrane, power (7-22 W), concurrent adenoidectomy, age, diagnosis (AOM vs OME), type of effusion, and preoperative tympanogram characteristics. Results are based on the number of ears that could be evaluated at each data collection interval. RESULTS: Fenestrations remained patent for 2 to 4 weeks (mean = 2.52, median = 2.0, SD = 1.4, n = 201); 97.4% were closed at 6-week follow-up. Spot sizes of 2.4 and 2.6 mm had a higher rate of patency than 2.0-mm spot size at 3 weeks following LTMF. Cure at 90 days was related to duration of patency for all patients combined and for patients treated for AOM and OME, but not for those undergoing adjunctive adenoidectomy. Cure at 90 days was related to larger spot size for all patients combined and those treated for AOM. Other investigated factors did not achieve statistical significance. CONCLUSIONS: Spot size of 2.4 mm or greater results in improved duration of LTMF patency, persisting for up to 3 weeks after LTMF, especially for treatment of AOM. Increased duration of LTMF patency correlates with greater incidence of cure of middle ear effusion at 90 days. Additional investigation is indicated to determine optimum spot size and optimum duration of patency for disease- severity-adjusted populations.

Acute Disease↗

Rapid identification of pickle yeasts by fluorescent PCR and microtemperature-gradient gel electrophoresis.

Monitoring the yeast populations within pickle soaking fluid is imperative for ensuring optimum taste, but these analyses have proven time-consuming and expensive, limiting their industrial application. Here, yeasts were identified in the soaking fluid from Japanese radish pickles using fluorescent PCR amplification of the variable D1/D2 region of the 26S rDNA, followed by analysis with microtemperature-gradient gel electrophoresis (micro-TGGE). This smaller version of the normal TGGE apparatus is capable of analyzing samples 10- to 20-fold faster without sacrificing data quality. Each primer set was labeled with a different fluorescent dye, allowing easy isolation of the various PCR products and identification of the bands corresponding to the various yeasts. The results indicate that fluorescent PCR and micro-TGGE may be a useful new method for rapid, easy monitoring of yeast flora in various food industries. This new method can be used on a daily basis to provide overviews of yeast flora during pickle production, allowing producers to quickly grasp pickle readiness at a single glance.

DNA Primers↗

Evolution of mechanoregulation of bone growth will lead to non-optimal bone phenotypes.

Mechanical forces acting on the bones during growth affect their final shape and strength. Mechanoregulation of bone growth may be recognized in embryogenesis, and also in the adaptation of the adult skeleton to changes in mechanical loading. Mechanoregulatory responses for tissues have arisen during evolution, but does evolution give rise to responses that produce optimal skeletal phenotypes? In this paper, we investigate the emergence of an optimal mechanoregulation response in a population. By combining equations describing long bone growth with a genetic algorithm to describe evolutionary change, we created a computational model to simulate the evolution of mechanoregulation in bone growth. A population of individuals is created where each individual is assigned a diploid gene set which controls the growth and remodelling of the bone. At maturity, each bone is assessed and its 'fitness' calculated; fitness is quantified as bone strength relative to bone mass. The simulation continues for many generations, and includes mutations and a varying environment. The genes present in the population are tracked and the evolution of parameters governing mechanoregulation is calculated. The results indicate that a population may converge to one bone growth algorithm but, more usually, a range of mechanoregulation algorithms for different individuals will persist after many generations. Even if the population converges to one mechanoregulation law, convergence to the 'optimum' bone was never found. Although many researchers propose that natural selection has pushed skeletal structure towards an optimum, our computational model suggests that this is unlikely to be the case.

Adaptation, Physiological↗

High-frequency mechanical ventilation principles and practices in the era of lung-protective ventilation strategies.

The term high-frequency ventilation is used to describe a heterogeneous group of ventilation modes that are characterized by high respiratory frequencies and low tidal volumes. The increasing understanding of the pathogenesis of VILI, including concepts such as volutrauma and atelectrauma, has led to a renewed interest in the role of HFV in lung-protective ventilation strategies. Inherent to many modes of HFV are low tidal volumes and small pressure swings during the respiratory cycle, which allow for higher mean airway pressures than those safely achieved with CMV. This has the potential to reduce lung injury by limiting volutrauma, whereas maintaining bigger lung volumes at end-expiration may reduce atelectrauma. Of the various forms of HFV, HFO is the only mode with an active expiration phase. This characteristic, combined with superior gas conditioning, may make HFO a promising ventilatory strategy for adults. Although a significant amount of data exists in the literature to support the application of HFO in infants and children who have acute respiratory failure, clinical data on the use of HFO in adults is only now emerging. Early studies of applying HFO in ARDS patients have demonstrated its safety and benefit in terms of oxygenation. Additionally, limited data exist on the comparison between HFO and CMV in this patient population; however, encouraging preliminary results have been reported. The optimum strategy for the application of HFV, including the timing of HFV initiation, remains unclear.

Barotrauma↗

Developmental constraints and wing shape variation in natural populations of Drosophila melanogaster.

The body sizes and shapes of poikilothermic animals generally show clinal variation with latitude. Among the environmental factors responsible for the cline, temperature seems to be the most probable candidate. In the present work we analysed natural populations of Drosophila melanogaster collected at different geographical localities to determine whether the same selective forces acting on wing development in the laboratory are also at work in the wild. We show that the temperature selection acting on wing development in the laboratory is only one of the selective forces operating in the wild. The size differences between natural populations seem to depend exclusively on cell number whereas they depend on cell area in the laboratory. The two wing compartments behave as distinct units of selection subjected to different genetic control, confirming our previous observations on laboratory populations. In addition, subunits of development defined as regions of cell proliferation centres restricted within longitudinal veins can, in turn, be considered as subunits of selection. Their interaction during development and continuous natural selection around an optimum could explain the high wing shape stability generally found in natural populations.

Animals↗

Latest advances and topics in fetal echocardiography.

PURPOSE OF REVIEW: Fetal diagnosis and the supporting specialties of perinatology, neonatology, and surgery have made rapid strides in the last decade. Numerous centers are focusing on this multifaceted niche area as the medical field realizes its vast promise and potential. The authors review some of the major advancements in thought and practice in the field of fetal echocardiography while attempting to give a less detailed overview for the less involved perinatologist. RECENT FINDINGS: First trimester fetal echocardiography has been an area of recent interest as transducer technology improves. As a result, optimum timing of first and subsequent scans and the population profile they are to be applied to have become an issue that begs consensus. Three-dimensional and four-dimensional fetal echocardiography have also received a boost for the same reasons, and both are being studied for feasibility and accuracy. Fetal tissue Doppler and spectral Doppler imaging are potential areas for exploration; the early steps have been taken. Awareness of associated ultrasound markers, such as exaggerated nuchal translucency, as clues to the presence of congenital heart disease is important, even if controversial. SUMMARY: The issue of missed prenatal diagnosis is disturbing, especially when it arises against a background of tremendous skill and technologic support. Strategies to minimize mistakes in this critical aspect need to be agreed on by the involved teams and put in place in a multidisciplinary manner if they are to have an important impact.

Echocardiography↗

Optical design of intraocular lenses. I. On-axis performance.

The theoretical effect of intraocular lens shape on on-axis performance of model pseudophakic eyes was investigated. Image quality criteria included the magnitude of spherical aberration (both wave and longitudinal), spot diagrams, and the modulation transfer function. For eyes with corneal asphericities encompassing most of the population (Q greater than or equal to -0.5), the optimum lens form is close to being plano-convex, with the more curved surface facing the cornea.

Lenses, Intraocular↗