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The vitamin A spectrum: from deficiency to toxicity.

Dark adaptation has been used as a tool for identifying patients with subclinical vitamin A deficiency. With this functional test it was shown that tissue vitamin A deficiency occurs over a wide range of serum vitamin A concentrations. However, serum vitamin A concentrations >1.4 micromol/L predict normal dark adaptation 95% of the time. Other causes of abnormal dark adaptation include zinc and protein deficiencies. Stable isotopes of vitamin A and isotope-dilution techniques were used recently to evaluate body stores of vitamin A and the efficacy of vitamin A intervention programs in field settings and are being used to determine the vitamin A equivalences of dietary carotenoids. Vitamin A toxicity was described in patients taking large doses of vitamin A and in patients with type I hyperlipidemias and alcoholic liver disease. Conversely, tissue retinoic acid deficiency was described in alcoholic rats as a result of hepatic vitamin A mobilization, impaired oxidation of retinaldehyde, and increased destruction of retinoic acid by P450 enzymes. Abnormal oxidation products of carotenoids can cause toxicity in animal models and may have caused the increased incidence of lung cancer seen in 2 epidemiologic studies of the effects of high-dose beta-carotene supplementation. Major issues that remain to be studied include the efficiency of conversion of carotenoids in whole foods to vitamin A by using a variety of foods in various field settings and whether intraluminal factors (eg, parasitism) and vitamin A status affect this conversion. In addition, the biological activity of carotenoid metabolites should be better understood, particularly their effects on retinoid signaling.

Animals↗

A nonlinear adaptive fuzzy approximator technique with its application to prediction of non-stationary EEG dynamics and estimation of single-sweep evoked potentials.

In this paper, we apply a fast training paradigm to the optimization of fuzzy approximator and a nonlinear adaptive fuzzy approximator (NAFA) is constructed. Using TSK fuzzy rules, the structured knowledge along with numerical information are parameterized and utilized in the NAFA, which can be easily configured as a multi-layer network when its transparency is desired. We propose a fast training paradigm, which is actually a combination of Kalman filtering and LMS adaptation, to optimize the linear and nonlinear parameters of the NAFA separately. The NAFA is characterized by concise representation of structured knowledge, fast learning capability, as well as universal approximation property. The NAFA is applied to forecast the non-stationary EEG time-series and to estimate single-sweep evoked potentials (EPs). The corresponding simulation results are given. It is concluded that the NAFA technique can provide efficient nonlinear separation of single-sweep EPs, which allows for quantitative examination of the cross-trial variability of clinical EPs.

Artifacts↗

[Identification of subjects at high risk of coronary disease in a working population using a prediction model].

Identification of subjects at high risk of coronary morbidity is of major interest in the prevention of cardiovascular disease. This report describes the use of a multifactorial prediction model for the identification of high risk subjects in a French male population. The PCV-METRA study (Prévention Cardiovasculaire en Médecine du Travail) monitors risk factors of cardiovascular morbidity in a population of men and women employed in big companies in the Paris region. A model adapted from a prediction model conceived by K.M. Anderson et al. in the Framingham study was used. The modified model enables an estimation of individual coronary risk based on 7 factors: age, total cholesterol, HDL-cholesterol, systolic blood pressure, smoking, diabetes and presence of left ventricular hypertrophy, taking into account the relatively low prevalence of coronary heart disease in France. The population comprised 4,131 active men aged 30 to 65 years. The average risk at 5 years was estimated to be 1.6%. Subjects at high risk (over the 80th percentile of the risk distribution curve) usually had high blood pressures and cholesterol levels. However, nearly 30% of these subjects were neither hypertensive nor hypercholesteraemic. It is important to note that 3/4 of these smoked. Moreover, they also had low HDL-cholesterol levels. A risk table, derived from the Framingham model, is presented. This table allows estimation of individual risk at 5 years in men aged 30 to 65 years. In each age group, the comparison of individual risk with the percentiles of risk distribution in the PCV-METRA population allows identification of high-risk subjects. This study proposes a tool for identifying subjects at high risk of coronary morbidity in a French male population. This multifactorial model is particularly useful for detecting subjects with several borderline factors none of which overstep the usually accepted limits.

Adult↗

The ecological validity of pediatric neuropsychological tests of attention.

Neuropsychological tests are frequently used clinically to predict real-world, or adaptive functioning; however, there are too few data to support such predictions. The relationship between adaptive functioning and, in particular, attention tests, has not been documented. The present study sought to determine the association between several domains of attention and adaptive functioning in a heterogeneous clinical sample of 119 children. A significant omnibus canonical correlation (Rc=.54) indicated that attention and adaptive functioning are correlated even when controlling for intelligence. Tests of attention and adaptive functioning domains that give rise to the overall association are discussed in terms of their clinical utility.

Adolescent↗

Predictive motor learning of temporal delays.

Anticipatory responses can minimize the disturbances that result from the action of one part of the body on another. Such a predictive response is evident in the anticipatory increase in grip force seen when one hand pulls on an object held in the other hand, thereby preventing the object from slipping. It is postulated that such a response depends on predicting the consequences of the descending motor command, as signaled by efference copy, using an internal model of both one's own body and the object. Here we investigate how the internal model learns the temporal consequences of the motor command. We employed two robots to simulate a virtual object held in one hand and acted on by the other. Delays were introduced between the action of one hand on the object and the effects of this action on the other hand. An initial reactive grip force response to the delayed load decayed with the development of appropriate anticipatory grip force modulation. However, no predictive modulation was seen when the object's movement was not generated by the subject, even when the motion was cued by a tone. These results suggest that, when an internal model learns new temporal relationships between actions and their consequences, this learning involves generating a novel response rather than adapting the original predictive response.

Adult↗

Social support, coping, and depressive symptoms in a late-middle-aged sample of patients reporting cardiac illness.

This study tests a 1-year predictive model of depressive symptoms in a late-middle-aged sample of patients reporting diagnoses of cardiac illness. Results based on 325 individuals (248 men and 77 women) diagnosed with chronic cardiac illness, 71 individuals (52 men and 19 women) diagnosed with acute cardiac illness, and 219 healthy controls (129 men and 90 women) strongly supported the hypotheses. Compared with healthy persons, individuals with chronic and those with acute cardiac illness reported more depressive symptoms at follow-up. Women overall showed more depressive symptoms than did men, and women with cardiac illness were particularly vulnerable to behavioral manifestations of depressive symptoms. Integrative time-lag and prospective structural equation models indicated that, for individuals with cardiac illness, social support and adaptive coping strategies predicted fewer depressive symptoms.

Adaptation, Psychological↗

Predicting the motion after-effect from sensitivity loss.

The widely accepted disinhibition theory of the motion after-effect (MAE) proposes that the balance point of an opponent mechanism is changed by directional adaptation. To see if the post-adaptation balance point could be predicted from contrast adaptation, we measured threshold-vs-contrast (i.e., T-vs-C or dipper) functions, before and after adaptation to moving gratings. For test stimuli moving in the same direction, adaptation shifted the point of maximum facilitation (i.e., the dip) upwards and rightwards. For tests moving in the opposite direction, adaptation produced a similar, but smaller, shift. These shifts are consistent with a change in divisive gain control. They are also consistent with subtractive inhibition followed by half-wave rectification. We attempted to use transducer functions derived from these data to predict the strength of the MAE. When combined, gratings moving in the adapted and opposite directions appeared perfectly balanced (i.e., counterphasing) when the latter was given approximately 2% more contrast than was predicted on the basis of the derived transducers. This small under-prediction may be indicative of sensory recalibration. Finally, we found that adaptation did not alter the fact that low-contrast stimuli could be detected and their direction identified with similar accuracy. We conclude that both static and dynamic forms of MAE are primarily caused by a decreased sensitivity in directionally tuned mechanisms, as proposed by the disinhibition theory.

Adaptation, Biological↗

[Dynamic structure of the cardiac rhythm in the process of adapting to high-altitude hypoxia].

On the basis of dynamic series of RR intervals of electrocardiograms of healthy male test subjects exposed for a different period of time to high altitude hypoxia, autoregression clouds were built. The patterns of distribution thus obtained were compared with physical work capacity of the test subjects. It is suggested that when selecting people to work actively at high altitudes autoregression clouds can be used as quantitative estimates of their health state and as predictions of potential adaptation failures.

Adaptation, Physiological↗

Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy.

PURPOSE: Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutated Ig V(H) mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy. METHODS: We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase II study, Cancer and Leukemia Group B (CALGB) 9712. RESULTS: Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig V(H) mutational status to classify risk, there was no association between complete response rate with either unmutated Ig V(H) mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig V(H) unmutated patients as compared with the Ig V(H) mutated patients. Using the hierarchical classification of Döhner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk. CONCLUSION: These data demonstrate that high-risk CLL patients characterized by Ig V(H) unmutated (> or = 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig V(H) mutational status and interphase cytogenetics on treatment outcome.

Adult↗

Estimating genetic correlations from inbred strains.

Genetic correlations measure the extent of pleiotropic effects of polygenes on pairs of characters or the closeness of linkage between sets of loci influencing the traits and held in allelic (gametic) disequilibrium. Their importance for research lies primarily in predicting correlated responses of one trait to selection based on values for another, and secondarily in analyzing the complex organization of biological systems. Genetic correlations appear to limit the rate and set the direction of multivariate evolution. In view of this, efficient methods for estimating genetic correlations may be essential for understanding the role of behavior in adaptation and for predicting behavioral change in evolution. In this paper we present methods for the estimation of genetic correlations from inbred strain comparisons. Estimates from inbred strains are relatively easy to obtain and appear to be valid when compared to those derived from more demanding parent-offspring comparisons and to correlated responses to selection.

Alleles↗

Compared responses of rat lungs to step volume changes and to sinusoidal forcing.

Lung pressure-volume hysteresis of cat lungs has been found by Hildebrandt (J. Appl. Physiol. 28, 365-372, 1970) to be 20-50% larger than predicted from stress adaptation data on the basis of a viscoelastic model. We have reinvestigated this phenomenon in isolated rat lungs with a different approach, in which the approximation inherent to using a model is avoided : Lung transfer function was derived from the digitally-computed Laplace transform of the pressure decay following a step volume change and used to predict lung pressure-flow relationship in the frequency domain. The latter was expressed in terms of lung effective resistance (Rlc) and effective elastance (Elc), and compared to the observed values (Rl and El) in the frequency range 0.01-0.5 Hz. The measurements were made in 5 lungs at a transpulmonary pressure (Pl) of 0.5 kPa and in 5 others at a Pl of 0.8 kPa. Rl was found to be 23-41% larger than Rlc at Pl = 0.5 and 29-51% larger at Pl = 0.8. El did not differ significantly from Elc at Pl = 0.5 but was 14-28% larger at Pl = 0.8. These results are in good agreement with previous findings. The differences between Rl and Rlc are proportional to the reciprocal of frequency and, thus, correspond to a rate-independent dissipation. They are consistent with a yield stress of 3-6 Pa.

Animals↗

New directions for oculomotor research.

This paper reviews major trends in the study of the oculomotor system since Westheimer published his doctoral research on this topic 35 years ago. Westheimer introduced the use of linear system analysis for the study of eye movements, an approach used a great deal by others ever since. Westheimer himself abandoned this approach within a decade, in part, because this kind of analysis becomes ambiguous when predictive properties of oculomotor system performance become prominent. We discuss the implications of ignoring the prominence of predictive eye movements and describe recent evidence for their prevelence and power. This leads us to propose that a new approach to the study of oculomotor performance is required. We also discuss the recent trend to apply the "connectionist" (or "neural network") approach in studies of the oculomotor system, and point out that the "symbolic", rather than the "adaptive", nature of predictive eye movements makes successful extension of these models to oculomotor performance unlikely. Our new approach emphasizes the use of natural stimulation in subjects free from bodily restraints. Accurate measurement of eye, head and torso movements under such conditions has become possible recently and data obtained in this manner has led to the discovery of a number of unexpected characteristics of oculomotor system performance. These developments have encouraged us to abandon the modular view of the oculomotor system, popular since Dodge launched the modern era of oculomotor research in 1903, which postulates five, or more, largely independent "subsystems". We suggest that only two subsystems (a fast saccadic and a somewhat slower smooth) are used to fixate and track a central representation of objects located in three-dimensional space. We show that this two-subsystem approach is consistent with current knowledge of oculomotor system neuroanatomy and neurophysiology.

Adult↗

Validation of a model predicting spontaneous pregnancy among subfertile untreated couples.

OBJECTIVE: To provide external validation of the Eimers model, which predicts spontaneous pregnancy among subfertile couples within the first year after the definitive establishment of the diagnostic category. DESIGN: Live birth rates predicted by an adapted version of the Eimers model were tested against observed live birth rates in a Canadian cohort study. SETTING: Fertility clinics in university medical centers. PATIENT(S): One thousand sixty-one couples consulting for subfertility due to cervical hostility, male subfertility, or unexplained subfertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We measured the discriminative ability and reliability of the predictions from the model. RESULT(S): The live birth rate was lower in the Canadian population than in the Eimers population. Overall, the prognostic effect of the predictors did not differ significantly in both populations. The model showed moderate predictive power in the Canadian population. With adjustment of the average live birth rate, the reliability of the model was satisfactory. CONCLUSION(S): The Eimers model gave reliable spontaneous pregnancy predictions in the Canadian validation population after adjustment of the average live birth rate.

Adult↗

Long-term executive function deficits in children with traumatic brain injuries: assessment using the Behavior Rating Inventory of Executive Function (BRIEF).

Long-term deficits in executive functions following childhood traumatic brain injuries (TBI) were examined using the Behavior Rating Inventory of Executive Function (BRIEF). Parents completed the BRIEF approximately 5 years postinjury as part of a prospective study of children injured between the ages of 6 and 12. The children were between 10 and 19 years of age at the time of the assessment, and included 33 with severe TBI, 31 with moderate TBI, and 34 with orthopedic injuries. Parents also rated children's adaptive functioning and completed several other measures of parent and family functioning. Children were administered a neuropsychological test battery that included several measures of executive functions. The groups displayed a significant linear trend in BRIEF scores, with the largest deficits in executive functions reported in children with severe TBI. BRIEF scores were related consistently across groups to a test of working memory, but not to other neuropsychological measures. BRIEF scores also predicted children's adaptive functioning and behavioral adjustment, as well as parent psychological distress, perceived family burden, and general family functioning. The findings indicate that TBI results in long-term deficits in executive functions that are related to children's psychosocial outcomes, as well as to parent and family functioning.

Brain Injuries↗

Efficiency of utilization of wheat and milk protein in healthy adults and apparent lysine requirements determined by a single-meal [1-13C]leucine balance protocol.

BACKGROUND: We recently reported better wheat-protein utilization and a higher apparent lysine requirement than would be predicted, because of adaptive mechanisms of lysine conservation. However, such findings may be subject to the feeding protocol of frequent small meals. OBJECTIVE: We used a [1-13C]leucine balance, large single-meal protocol to estimate the utilization of wheat and the consequent lysine requirements. DESIGN: Wheat and milk utilization were compared in 5 adults infused for 9 h with L-[1-13C]leucine, in the postabsorptive (0-3 h) and postprandial (3-9 h) states after ingestion of a single meal of either milk (30.4 kJ/kg; 32% of energy as protein) or a mixture of wheat gluten and whole wheat (29.2 kJ; 26.7% of energy as protein). Premeal nitrogen balance was predicted from [1-13C]leucine oxidation and postmeal balance predicted from cumulative increased leucine oxidation, enabling evaluation of the metabolic demand for protein, the efficiency of postprandial protein utilization (PPU), and the requirements for wheat protein and lysine. RESULTS: Mean (+/-SD) PPU was 0.61 +/- 0.03 and 0.93 +/- 0.02 for wheat and milk (P < or = 0.001), respectively, and the estimated average wheat-protein requirement (0.6 g.kg(-1).d(-1)/PPU) was 0.98 +/- 0.05 g.kg(-1).d(-1), indicating a lysine requirement of 18.3 +/- 1.0 mg. kg(-1).d(-1). CONCLUSIONS: Measured wheat utilization efficiency at 0.61 was considerably higher than the value predicted from wheat lysine intake and milk protein lysine deposition (ie, 0.222 +/- 0.004). These results confirm our previous finding that lysine conservation allows wheat protein to be utilized more efficiently than expected and is consistent with a lysine requirement in fully adapted individuals of 19 mg.kg(-1).d(-1), as indicated by recalculated nitrogen balance data.

Adult↗

The predictive value of stress shielding for quantification of adaptive bone resorption around hip replacements.

The presence of a femoral hip stem changes local mechanical signals inside the surrounding bone. In this study we examined the hypothesis that the eventual loss of bone can be estimated from the initial patterns of elastic energy deviation, as determined in FE models of the intact bone and the operated femur. For that purpose two hypothetical relations between elastic energy reduction and resorption were investigated. Their estimates of bone loss were compared to the results of iterative computer simulations. Two kinds of FE model were used, and in each stem stiffness and remodeling threshold (a measure of "biological reactivity") were varied. Provided that reasonable values of the remodeling threshold are assumed and that the stem is firmly bonded to the bone, we found that the difference between direct estimates and simulation models was 4 percent of bone loss. It is therefore concluded that initial patterns of elastic energy deviation give a reasonable indication of expected bone loss.

Adaptation, Physiological↗