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How good is the match between the plane of the text and the plane of focus during reading?

Because results from animal models demonstrate that retinal image defocus is a crucial factor in the visual control of eye growth, we have measured the precision of accommodation during reading at 1 m and at 30 cm distance. A newly developed photorefractor was used to sample both the refraction in the vertical meridian and direction of gaze at 25 Hz. Using these two parameters, a three-dimensional "refraction map" of the visual field was plotted. It showed the optic disc as an area with more myopic refractions and the course of refractions across a visual field of about +/- 25 deg. A special calibration scheme was employed to ensure that the precision of the refractions was 0.2 dpt or better (as estimated from the standard deviations of repeated measurements and the noise in the calibration curve). Twelve young adults (students from the lab) served as subjects. We found considerable inter-individual variability in the off-axis refractions but little variability among repeated measurements in the same subjects. Inter-individual variability reached a minimum in the foveal region. Both myopes wearing their spectacle corrections (n = 6) and emmetropes (n = 6) under-accommodated by about 0.3 D during reading at 30 cm distance but, at 1 m distance, only the emmetropes under-accommodated. Since both refraction groups under-accommodated similarly during reading at close distance, it remains unclear whether the small amount of defocus is critical for their future myopia development. Either accommodation errors differ at earlier times when myopia first appears (as suggested by the literature), or the subjects' eye growth was differently sensitive to defocus, or our simple protocol did not pick up existent differences in accommodation among the two groups.

Accommodation, Ocular↗

Hypothalamic multiunit activity and pulsatile luteinizing hormone release in the castrated male rat.

Using chronically implanted microelectrodes, multiunit electrical activity (MUA) was recorded from the arcuate nucleus of freely moving gonadectomized male rats. Intermittent increases in MUA activity (MUA volleys) closely associated with luteinizing hormone pulses measured in the peripheral circulation were observed, which confirms that this experimental approach can be used for monitoring the activity of the gonadotropin-releasing hormone-associated hypothalamic pulse generator in the male rat. The mean MUA volley frequency was 22.2 min (range 13-38 min), whereas the mean MUA volley duration was 2.7 +/- 0.8 min (standard deviation). In addition to a large inter-individual variability. MUA volley intervals also showed an important intra-individual variability. This observation suggests that, beside the mean frequency of pulse generator activation, the degree of variability in gonadotropin-releasing hormone-associated pulse generator activity might be an additional relevant parameter in the characterization of the reproductive function in the male rat.

Animals↗

Variables discriminating individuals who seek orthodontic treatment.

Overall, these results support the view that dental-facial esthetics and self-perceptions of occlusal appearance, as well as attitudes toward malocclusion and orthodontic treatment, are important factors in the individual's decision to obtain orthodontic treatment. The data indicate that psychosocial variables not directly related to occlusal problems and treatment, do not add significantly to the description of differences between those who seek treatment and those who do not. While these analyses did not include a number of variables--such as socioeconomic factors or attitudes of significant others--which may also be important in predicting individual response to malocclusion, they do suggest strongly that psychosocial factors directly related to need for treatment are probably most productively assessed in terms of self-perceptions of occlusal appearance and attitudes regarding dental malrelations and their treatment.

Adolescent↗

[Predictive factors of minimally effective nCPAP ventilation in treatment of obstructive sleep apnea?].

BACKGROUND: Nasally applied continuous positive airways pressure (nCPAP) ventilation is an effective treatment of obstructive sleep apnoea syndrome (OSAS). As the lowest effective nCPAP-level (nCPAPmin) inter-individually is quite variable individual pressure titration under polysomnographic monitoring is necessary. AIM: To determine whether nCPAPmin can reliably be predicted on the basis of clinical and polysomnographic variables. PATIENTS AND METHODS: A set of 77 unselected OSAS-patients was investigated in the sleep laboratory. We used a standard sleep-related questionnaire, examined anthropometric variables, performed lung function tests and blood gas analyses, and measured nasal cross-sectional area as well as nasal flow resistance. In the night prior to the nCPAP titration a cardiorespiratory polygraphy was performed. Stepwise multiple regression analysis using the titrated nCPAPmin as dependent variable and the clinical and polygraphic data as independent variables revealed gender (GES), neck circumference (NCF), body mass index (BMI), and apnoea-/hypopnea index (AHI) as the optimal set of predictors of nCPAPmin in this model. RESULTS: Multiple regression analysis with these factors yielded the following equation: predicted nCPAPmin = 1.95 + 0.80 x GES + 0.09 x BMI + 0.01 x NCF + 0.03 x AHI (woman: GES = 1; man: GES = 2). The reliability of the equation was tested with a second set of 180 prospective OSAS-patients. In these patients the mean nCPAP-level as titrated in the sleep laboratory was 9.1 +/- 2.0 mbar, whereas the mean predicted nCPAP-level was 8.4 +/- 3.6 mbar (p = n.s.). In 51% of the patients the difference between nCPAPmin measured and predicted was greater than +/- 1 mbar. CONCLUSION: This equation is neither sufficient to reliably predict nCPAPmin nor to prescribe nCPAP without individual pressure titration. The calculated nCPAP-level might however contribute to choosing the most suitable flow generator prior to the titration night.

Adult↗

Patterns of genetic variability at individual minisatellite loci in minke whale Balaenoptera acutorostrata populations from three different oceans.

The genetic variability at six cloned minisatellite loci was analyzed in minke whale populations from the North Atlantic, North Pacific, and Antarctic Oceans. Three loci displayed only a few different alleles in each of the three populations, with heterozygosity ranging from 0.00 to 0.47, and three loci revealed many different alleles in at least two fo the three populations, with heterozygosity ranging up to 0.98. Using small sample sizes, samples from two adjacent Antarctic Management Areas were not found to differ significantly in allele frequencies at any of the six loci. The use of principal coordinate analysis to detect multilocus disequilibria was explored. No significant evidence was found of intrapopulation heterogeneity within the pooled Antarctic sample. Pronounced interoceanic differences were observed at every locus, confirming the existence of genetic isolation found earlier using more conventional marker systems. The populations from the three oceans appear to have diverged to such a degree that the hypervariable loci have had time to evolve independently and arrive at different evolutionary stages in different populations. The frequency of undetected "null" alleles is remarkably high in minke whale populations compared to human populations and is probably a result of the cloning protocol used. Minisatellite loci are shown to provide a powerful population genetic tool, supplying levels of resolution appropriate to different degrees of evolutionary divergence.

Alleles↗

Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD): A collaborative platform for behavioral analysis across the lifespan.

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data from multiple laboratories. ID-CARD is designed to support large-scale, integrative analyses and to facilitate secondary use of existing behavioral data in alignment with emerging data-sharing and transparency initiatives. Rather than imposing retrospective harmonization of experimental protocols, we implemented a normalization and modeling framework that enables comparison of learning trajectories while preserving meaningful variation across studies. Behavioral data from > 5000 rats spanning common strains, both sexes, and multiple ages were normalized in training and performance domains and fit with a logarithmic function to derive an error accumulation rate coefficient (EARC) as a measure of spatial learning. Age was strongly associated with increased EARC, indicating attenuated learning, even after adjusting for non-spatial cue performance. Analyses of goodness of fit revealed systematic structure in learning dynamics, where age was associated with reduced learning-curve conformity after accounting for overall performance. Inter-individual variability in spatial learning also increased with age, with strain-specific interactions. These findings demonstrate that integrated analysis of heterogeneous behavioral datasets can yield robust, individual-level insights into cognitive aging. ID-CARD provides a scalable resource and analytic framework to advance discovery in behavioral neuroscience by enabling reuse, integration, and comparative analysis of existing data.

Cognitive aging↗

Development and Validation of a Novel LC-MS/MS Based Proteomics Method for Quantitation of Retinol Binding Protein 4 (RBP4) and Transthyretin (TTR).

Retinol binding protein 4 (RBP4), the circulating carrier of retinol, complexes with transthyretin (TTR) and is a potential biomarker of cardiometabolic disease. However, RBP4 quantitation relies on immunoassays and western blots without retinol and TTR measurement. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous absolute quantitation of circulating RBP4 and TTR is critical to establishing their biomarker potential. Surrogate peptides with reproducible, linear LC-MS/MS response were selected. Purified proteins were used as quantitation standards and heavy-labelled peptides as internal standards. Matrix effects were evaluated. The validated method was applied to measure inter- and intra-individual variability in RBP4 and TTR concentrations in healthy individuals and patients with diabetic kidney disease. Quantitation was linear for the clinically relevant concentration ranges of RBP4 (0.5-6 &#x3bc;M) and TTR (5.8-69 &#x3bc;M). Assay inter-day variability was <12% and precision within 5%. The inter-individual variability for RBP4 and TTR concentrations was 18-26%, while intra-individual variability was similar to assay variability. RBP4 and TTR quantitation correlated with commercially available ELISA assays. The developed LC-MS/MS method enables simultaneous absolute quantitation of RBP4 and TTR in serum and plasma that can be applied to clinical biomarker studies and stoichiometric measurements of circulating RBP4, TTR, and retinol.

Retinol binding protein 4 (RBP4)↗

Influence of naloxone on the postoperative analgesic and respiratory effects of buprenorphine.

Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fraction 60%; Group BN) in the early postoperative period by means of the On-Demand Analgesia Computer (ODAC). The duration of patient-controlled analgesia (PCA) was 21.0 h (B) or 23.5 h (BN), during which 12.2 (B) and 18.2 (BN) demands per patient were recorded, representing significantly different consumption of buprenorphine 0.80 (B) and 1.07 (BN) microgram.kg-1.h-1. Retrospective pain scores were significantly better in Group B, and respiratory rate was significantly higher in Group BN. The analgesia was judged superior by 81% (B) and 88% (BN) of the patients compared to conventional postoperative pain treatment. The minimum effective buprenorphine concentration (MEC) varied greatly in both groups with no significant differences between them (median 0.4 ng.ml-1, range 0.1-8.6 ng.ml-1); intra-individual variability was lower (67.9% B, and 58.2% BN) than inter-individual variability (107.3% B and 84.0% BN). Accumulation in plasma and acute tolerance did not occur. Thus, admixture of 60% naloxone decreased both the analgesic and respiratory depressant effects of buprenorphine which were generally independent of plasma concentrations. The analgesia achieved with the buprenorphine/naloxone mixture under patient-controlled conditions was comparable to that of other narcotic analgesics. Accordingly, this drug combination may be expected to give clinically adequate analgesia without notable impairement of spontaneous respiration, whilst withdrawal symptoms would probably arise in drug addicts abusing other opiates.

Blood Pressure↗

Mathematical study of the contamination phenomenon in the culture of tubercle bacilli.

This paper demonstrates that when 'spot' specimens of sputum are cultured for tubercle bacilli on Löwenstein-Jensen medium, bacterial contamination occurs at random and follows a Poisson distribution. Over a period of 14 years, contamination rates with overnight 'collection' specimens (4.5 to 10.2%) were substantially higher than with spot specimens (1.3 to 4.0%), but the correlation between the two was very high (r = 0.98). In contrast to spot specimens, the incidence of contamination with collection specimens was significantly higher for females than for males, and significant variation was also found between patients of the same sex. In consequence, the Poisson distribution, which assumes a constant contamination rate for all patients, did not provide a satisfactory fit to the data on collection specimens. However, a negative binomial distribution, which incorporates individual variability in contamination rate, provided a good fit. The reasons for individual variability are discussed.

Bacteriological Techniques↗

Hippocampal acetylcholine and habituation learning.

Acetylcholine neurotransmission is considered to play a critical role in processes underlying behavioural activity, arousal, attention, learning, and memory. These functional attributions have largely been based on pharmacological findings. or data from brain damaged animals, and humans with neurodegenerative diseases, such as Alzheimer's disease. With the introduction of the in vivo microdialysis method it has recently become possible to monitor acetylcholine in the brain of the behaving animal, which allows to investigate its activity in specific behavioural tasks. With respect to learning and memory, one of the most elementary experimental paradigms is that of behavioural habituation, where the decrease of exploratory activity as a function of repeated exposure to the same environment is taken as an index of memory. We have used this paradigm to monitor hippocampal acetylcholine levels by means of in vivo microdialysis in rats, which were exposed to a novel open field and which were re-exposed to it on the following day (10 min each). The results show that exposure of rats to the novel environment led to increased extracellular levels of hippocampal acetylcholine which were positively correlated with exploratory behaviour. These cholinergic activations were larger than those of control animals which were handled like the experimental animals but which were not exposed to the open field. When re-exposing the experimental animals to the same environment, exploratory behaviour, but not cholinergic activation, was decreased. indicating habituation. In the subsequent 10 min, that is, when the animals where back in their home cages, cholinergic activity was still increased. The magnitude of increase was larger after re-exposure than after exposure to the novel open field. Finally, we differentiated the animals into "superior" vs "inferior" learners and found that the "superior" learners showed higher behavioural activation in the novel environment and stronger neurochemical responses, both. in the novel and familiar environment. Our data show that extracellular levels of hippocampal acetylcholine are not only elevated in relation to novelty and behavioural activation. but also during behavioural habituation. Furthermore, an inter-individual variability of cholinergic activation seems to exist which is related to individual differences in behavioural responsiveness to novelty. Such differences in cholinergic activity may be related to other known differences in hippocampal structure and function and may be important for previously reported inter-individual variabilities in sensation-seeking and related mnestic functions.

Acetylcholine↗

Statistical methods for population pharmacokinetic modelling.

A principal aim of population pharmacokinetic studies is to estimate the variance components associated with intra- and inter-individual variability in observed drug concentrations. The explanation of the inter-individual variability in terms of subject-specific covariates is also of great importance. Pharmacokinetic models are nonlinear in the parameters and estimation is not straightforward. Within this paper we review a number of estimation approaches which have been suggested for population pharmacokinetic analyses. We distinguish between Bayesian and non-Bayesian and fully-parametric, semi-parametric and nonparametric methods.

Analysis of Variance↗

Variability of tumor markers in the follow-up of patients radically resected for breast cancer.

The biological and analytical components of variability of tumor markers should be distinguished from the variations due to tumor progression. The aim of the present study was to evaluate tumor marker variability in the follow-up of patients resected for breast cancer. So far, we have carried out 2,085 CEA and 2,550 CA 15-3 determinations in 435 patients. The total variability of both CEA and CA 15-3 was widely scattered among different subjects (CEA coefficient of variation 0-105%; CA 15-3 coefficient of variation 0-89.2%). The biological variability of CA 15-3, which was calculated in a limited number of cases, was scattered between 0 and 23% and was higher than the intra-assay variability. From these findings we conclude that when evaluating serial marker assays the intra-individual variability should be assayed initially to obtain a reference value of individual variability in relapse-free conditions.

Analysis of Variance↗

Bladder reservoir function in children with monosymptomatic nocturnal enuresis and healthy controls.

PURPOSE: We investigated bladder reservoir function in children with monosymptomatic nocturnal enuresis and in healthy controls. MATERIALS AND METHODS: A total of 18 children with monosymptomatic nocturnal enuresis and 119 controls who were 7 to 13 years old were recruited. Children completed frequency volume charts and measurements of nocturnal urine production. Mean diuresis in the period preceding each voiding was calculated. Those with enuresis were grouped according to bladder capacity and hospitalized for 4 nights, including a baseline night and 3 with an oral water load. Enuresis volumes and post-void residual volume were estimated, allowing the calculation of bladder volume at the time of enuresis. RESULTS: Nine children with monosymptomatic nocturnal enuresis were characterized as having normal bladder capacity and 9 had decreased bladder capacity. We found large intra-individual variability in daytime voided volume in all 3 groups of participants. Children with enuresis and small bladder capacity generally voided with volumes close to maximal voided volume. A total of 93 enuresis episodes were recorded. Large intra-individual variability was seen in bladder volume at enuresis and it was lower than maximal voided volume in more than 50% of episodes. Variability in bladder volume at enuresis was greatest in the patient group with decreased bladder capacity. We found a significant correlation between diuresis and bladder capacity in all groups during the day and night. CONCLUSIONS: There is a great intra-individual diurnal variability in voided volume in children with enuresis and in healthy children. Enuresis seems to occur at bladder volumes that are smaller and larger than the maximal voided volume obtained from voiding charts.

Child↗

[Variability of the sulci and gyri of the inferior parietal region of the human brain in ontogeny].

Individual variability in the form of the inferior parieto-occipital gyri has been studied in 130 hemispheres of fetuses, children and grown-up persons beginning from 4 months of the intrauterine life up to 55 years of age. Differences in the form of the gyri have been noted already in the prenatal period; after birth, the process on complicating their configuration is continuing. Despite variety in their form, it is possible to reveal some peculiar U-like, III-like and transitive variants. Taking into account correlative dependence existing between the cortical fields size and the size of corresponding gyri, an applied importance of their individual variability could be supposed.

Adolescent↗

Variability of neoplastic parameters in colon tumours, and its significance in diagnostic practice.

We have reviewed the value of individual variability in the reaction of tissues to treatment with carcinogens, and the manifestation of this variability in different morphological (histological, morphometric, and ultrastructural), histochemical and immunohistochemical parameters generated in tumorous tissues. Moreover, we also reviewed data in the literature on individual variability in the manifestation of some biochemical and immunochemical markers which are accumulated in the serum of tumour-bearing patients and which are characteristic for the different phases of tumourigenesis. The high variability of different tumorous parameters suggests that none can be utilized alone as a conclusive marker of neoplasia and that only their combined use can give objective information. We also reviewed the impact of this variability in the evaluation of various pathological methods to detect different stages of neoplastic transformation in the colon. It has been concluded that none of the present approaches can be absolutely conclusive and without false results, and that objective information regarding early cancerous changes may be obtained only by use of combined analyses utilizing several laboratory methods. The diagnostic procedures should be based on the complex utilization of all appropriate methods using the quantitative interpretation of the obtained data. Multivariate analysis of many parameters should be very effective for the prediction of therapeutic results.

Animals↗

Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous response modifiers.

BACKGROUND: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? METHODS: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD 5/5). Fifty-five questionnaires (21.5%) were answered. RESULTS: Empirically, the most important endogenous factors to modify the acute tissue tolerance are a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), b) collagen diseases (9 a/37%) and c) immune diseases (5 a/53%). As endogenous response modifiers for the TD 5/5 are recognized a) metabolic or other diseases leading to macro- or microangiopathia (15 a/31%), b) collagen diseases (11 a/38%) and c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD 5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are a) smoking (34 a/44%), b) alcohol (23 a/45%), c) nutrition/diets (16 a/45%), d) hygiene (9 a/26%) and e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD 5/5 are a) smoking (22 a/40%), b) alcohol (15 a/38%), c) nutrition/diets (9 a/48%), d) hygiene (5 a/34%) and e) medical therapies (10 a/30%). CONCLUSIONS: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response.

Alcohol Drinking↗

Effect of the potentiation of cholinergic activity on the variability in individual GH response to GH-releasing hormone.

In man the GH response to GHRH is highly variable and some normal subjects may be completely unresponsive to the neuropeptide. On the other hand, the potentiation of cholinergic activity by pyridostigmine (PD), a cholinesterase inhibitor, increases the GH response to GHRH, probably by inhibiting somatostatin release. The aim of this study was to assess the existence of intraindividual variability in the GH response to GHRH and verify the effects of PD treatment on inter- and intraindividual variability. Twenty normal adults (17 M and 3 F) and 10 normal prepubertal children (9 M and 1 F) underwent 2-5 administrations of 1 micrograms/kg GHRH on different days. Seven adults and all children also underwent 1-5 other tests in which GHRH was preceded (60 min before) by oral PD (120 mg in adults and 60 mg in children). The GH responses to GHRH were highly variable, not only within subjects but also in the same subject on different occasions (peak range; adults: 0.4-49.0 ng/ml; children: 2.4-50.0 ng/ml). PD always markedly increased the GH response to GHRH, even unmasking this response in 3 adults and 4 children hyporesponsive to the neuropeptide alone. However, the variability in the GH response was still present (adults: 27.2-108.5 ng/ml; children: 25.0-144.0 ng/ml), though reduced (adults: p = 0.0005; children: p = 0.0204). These data indicate that: i. A great inter- and intraindividual variability in the GH response to GHRH is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The selection of anterior teeth appropriate for the age and sex of the individual. How variable are dental staff in their choice?

As part of the development of a guide to aid the undergraduate in the selection of artificial teeth, the aim of this study was to investigate the variability in choice of dental staff to select teeth appropriate to the age and sex of the individual with the aid of a series of three-dimensional guides. Four three-dimensional guides were produced for use in the study. Fifty dentists were asked to complete a questionnaire designed to assess the variability in selection of anterior teeth appropriate for the age and sex of an individual. From this study it can be concluded that there was little consistency in the selection of the shade, mould and arrangement of anterior teeth appropriate for the age and sex of the individual by qualified dental staff. The development and implementation of an aesthetic proforma to guide dental staff, dental undergraduates and patients through the process of choosing tooth mould, shade and arrangement based on age and sex may be helpful.

Adult↗