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Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms.

OBJECTIVE: Impairments in adaptive life skills are a major source of disability in patients with schizophrenia. The relationship between adaptive life skills in real-world settings and performance on neuropsychological tests may be complicated by other factors that interfere with deployment of skills. Assessment of the ability to perform life skills under optimal conditions (i.e., assessment of functional capacity) has been proposed as a means to clarify these relationships. METHOD: The authors examined cross-sectional data from a study of the course of neuropsychological and adaptive life skills of older (age 50-85) schizophrenia patients (N=78). Functional capacity was examined with a performance-based measure (UCSD Performance-Based Skills Assessment), and case managers rated real-world adaptive functions (i.e., interpersonal skills, work skills, and community activities). Neuropsychological performance was assessed with a comprehensive battery, while symptoms were assessed with patient self-report and clinical ratings. RESULTS: Confirmatory path analyses were used to evaluate the effects of neuropsychological performance, functional capacity, and symptoms on the various domains of real-world functioning. Neuropsychological performance predicted functional capacity, which predicted all three domains of real-world functioning. Depression predicted interpersonal and work skills, while negative symptoms affected interpersonal skills independently of other predictors. CONCLUSIONS: Real-world adaptive life skills are predicted by neuropsychological performance, symptoms, and functional capacity. Neuropsychological performance contributes little to the prediction of real-world performance after accounting for functional capacity. In some domains, negative and depressive symptoms influenced real-world performance while not relating to functional capacity or neuropsychological performance.

Activities of Daily Living↗

A new approach to understanding adaptive visual-vestibular interactions in the central nervous system.

Recent neurophysiological findings, cited in previous publications imply that some vestibular commissural pathways may form positive feedback loops across the midline. It has already been shown theoretically that such feedback coupling of the vestibular nuclei could play an important role in the realization of the central integrator in the vestibuloocular reflex (VOR). In addition, it was found that known commissural plasticity during vestibular compensation, if placed at the level of such cross-midline loops, could reconcile findings after labyrinthine lesions. This paper examines theoretically the role such commissural feedback loops could play in the adaptation of the dynamics of the VOR in normal behaving animals. A simple static example is used to illustrate that changes in synaptic efficacy along cross-midline feedback loops could serve to adjust both balance and gain in vestibular reflexes. A bilateral model of the VOR and its interactions with vision is used to explore analytically the consequences of parametric changes along cerebellar and/or commissural pathways in three protocols: VOR in the dark, visual pursuit, and visual VOR suppression. Model predictions are systematically related to published findings after short- and long-term adaptation of the VOR. Conclusions arising from the theoretical results point to specific strategies that can be used in experiments on intact alert animals, in the further study of vestibular adaptation, and in the diagnosis of possible sites of plasticity. This should be relevant to arguments on cerebellar versus brain stem sites for vestibular adaptation, currently a highly controversial issue. For example, it is found that observations of responses in the adapted VOR in the dark are not sufficient to distinguish between a brain stem or cerebellar site for VOR plasticity. Also, the analysis shows that, in the model, changes in the VOR gain would often be associated with parallel changes in VOR dynamics; this has often been reported, but previously left unexplained. Model predictions of response changes in the adapted VOR, during VOR suppression, do provide a means of distinguishing between brain stem or cerebellar sites of plasticity; only the brain stem site, postulated here in the commissural loops, would produce cerebellar response changes compatible with the observations of Miles and Lisberger, during long-term adaptation of the VOR. A cerebellar site for VOR adaptation in the model would produce changes in cerebellar responses that would only be compatible with observations to date during rapid, or short-term (hours), modification of the VOR, as reported by Ito and his group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Perspectives: bone's mechanical usage windows.

As mechanical usage (MU) of a bone changes from complete disuse towards maximal vigor, the biologic mechanisms that can adapt it to its MU tend to react predictably. Acute disuse can increase BMU (Basic Multicellular Unit, the remodeling 'packet') creations but reduces how much bone they form, to increase bone loss next to marrow. Normal usage reduces those creations to normal and tends to equalize their resorption and formation; this conserves bone. In mild overloading, BMUs still conserve existing bone, while modeling drifts can begin adding to and/or reshaping it. Severe overloading can increase microdamage alarmingly, its repair by BMUs too, and can cause woven bone formation, anarchic resorption and a regional acceleratory phenomenon. Those ranges of MU vigor can define four 'windows'. An adapted window should apply to healthy, normally active adult mammals, and a mild overload window to healthy, normally active growing ammals. The biologic responses in the pathologic window could explain among other things some total joint and internal fixation failures, some pathologic fractures and some bone healing and sports medicine problems.

Adaptation, Physiological↗

The influence of rod light and dark adaptation upon rod-cone interaction.

The influence of a rod-detected mask of illuminance IR on the threshold illuminance of a cone-detected test flash (ICth) was assessed while rods were recovering from the effects of a bleach, and when rods were selectively light adapted. Providing that IR was restricted to within 2 log10 units of rod mask threshold (IRth), results show that ICth/IC0 = K (square root (IR/IRth) + D), where IC0 is cone absolute threshold, D is a dark noise term and K is a proportionality constant. These data were used to obtain 'equivalent background functions' or 'Crawford (1947) transforms' (illuminance of a background field plotted against time in the dark). The same Crawford transform was obtained when either IRth or ICth (in the presence of a fixed illuminance IR) were used as equating variables. All of the foregoing results could be predicted by considering both the influence of light adaptation on rods (see Fain, 1976) and the model developed by Bauer, Frumkes & Nygaard (1982). Under dark-adapted conditions, 40' and 60' diameter rod masks of equal illuminance have very similar influences on ICth. When rods are selectively light adapted 60' masks have smaller influences on ICth. The foregoing results were used to extend the model developed in the previous paper. We suggest that rod adaptation has a distinct influence on neural loci designated E (the excitatory spatial summator) and I (the inhibitory spatial summator), and that E represents a site for both adaptation and spatial summation.

Adaptation, Ocular↗

Dependence of reactive responses in human bimanual finger movements on sensory feedback and auditory cues.

We examined the effects of repetitive experience of feedback events and cue signals on adaptation of bimanual reactive response, both of which can be used to predict load forces on handheld objects. Normal human subjects used bimanual index fingers to hold two plates mounted on separate torque motors. Sensory-driven reactive forces from the fingers were measured during concurrent loading of both plates or isolated loading of the left plate. After repeated experiences of single load conditions, right and left fingers increased normal forces in a coordinated manner during concurrent loading, while the left finger responded almost exclusively during isolated loading of the left plate. However, after switching load conditions from concurrent to isolated load, or vice versa, several trials were needed to adapt to the new condition, as was clearly observed in the dynamic phase of responses from the right finger. Adaptation depends on the number of feedback experiences, and specifically on prediction error, showing intermediate predictions between the two conditions. Thus influences of the previous experiences show similar properties to those observed in self-generated movement, which were reported previously. In addition, auditory cues informing subjects of coming load conditions also partially adapted responses to these conditions. The neuronal center for reactive responses is therefore influenced by both previous experience and cue signals, inducing the appropriate responses for the predicted sensory inputs.

Acoustic Stimulation↗

Mastery motivation in young children with Down's syndrome: relations with cognitive and adaptive competence.

BACKGROUND: Prior research on relations between motivation and competence have focused on cognitive competence, despite theoretical predictions that mastery motivation spurs behaviour that is effective in meeting the demands of one's environment, i.e. adaptive competence. Issues of adaptive competence are especially relevant for children with developmental delay since functional independence is an important long-term goal for these children. METHODS: In the present study, mastery motivation was examined in relation to both cognitive and adaptive competence in 5-year-old children with Down's syndrome (n = 41). RESULTS: Scores on mastery task and parent-report measures of mastery motivation were generally low, but positively related to scores on standardized measures of cognitive competence and adaptive competence. CONCLUSIONS: This is the first study of motivation-competence relations in pre-school-age children. The findings have implications for both developmental theory and early intervention efforts, and the authors hope that they will serve as a stimulus for future research on cross-domain relationships in atypical populations.

Adaptation, Physiological↗

Comparing artificial and convolutional neural networks with traditional models for Genomic prediction in wheat.

With the rapid development of sequencing technology, the application of genomic prediction has become more and more common in breeding schemes of livestocks and crops. Selecting an appropriate statistical model is of central importance to achieve high prediction accuracy. Recently, machine learning models have been expected to upgrade genomic prediction into a new era. However, the perspective still suffers from lack of evidence that machine learning models can generally outperform the traditional ones on empirical data sets. In this study, we compared two machine learning models based on artificial neural network (ANN) and convolutional neural network (CNN) with four traditional models, including genomic best linear unbiased prediction (GBLUP), Bayesian ridge regression (BRR), BayesA and BayesB, using three published data sets for grain yield in wheat. For each model, we considered two variants: modeling and ignoring the genotype-by-environment ([Formula: see text]) interaction. In the comparison, we considered two strategies of cross-validation: predicting genotypes that have not been evaluated in any environment (CV1) and predicting genotypes that have been tested in other environments (CV2). Our results showed that traditional Bayesian models (BayesA, BayesB, and BRR) outperformed GBLUP, ANN and CNN when considering [Formula: see text] interaction. The accuracies of ANN and CNN were higher than traditional models only in CV1 and when [Formula: see text] interaction was ignored. It was also found that the performance of the two machine learning models was significantly affected by the interaction between the CV strategy and the way of treating the [Formula: see text] interaction, while that of the four traditional models was only influenced by whether the [Formula: see text] interaction was considered or not. Thus, machine learning models can be a powerful complementary to the traditional ones and their superiority may depend on the prediction scenario. Among the two machine learning models, we observed that the accuracy of ANN was higher than CNN in most cases, indicating that it is still challenging to adapt complex machine learning models such as CNN to genomic prediction.

ANN↗

Sexual strategies theory: an evolutionary perspective on human mating.

This article proposes a contextual-evolutionary theory of human mating strategies. Both men and women are hypothesized to have evolved distinct psychological mechanisms that underlie short-term and long-term strategies. Men and women confront different adaptive problems in short-term as opposed to long-term mating contexts. Consequently, different mate preferences become activated from their strategic repertoires. Nine key hypotheses and 22 predictions from Sexual Strategies Theory are outlined and tested empirically. Adaptive problems sensitive to context include sexual accessibility, fertility assessment, commitment seeking and avoidance, immediate and enduring resource procurement, paternity certainty, assessment of mate value, and parental investment. Discussion summarizes 6 additional sources of behavioral data, outlines adaptive problems common to both sexes, and suggests additional contexts likely to cause shifts in mating strategy.

Biological Evolution↗

Adaptive control of etoposide administration: impact of interpatient pharmacodynamic variability.

We sought to use a previously derived pharmacodynamic model for 72-hour etoposide infusions to adaptively control administration of this agent and to demonstrate that more predictable toxicity could be obtained with this dosing scheme. A randomized crossover study design was used to compare "standard" dosing (125 mg/m2/day) to adaptive control, with dose adjustment at 28 hours based on the 24-hour plasma level. A total of 31 patients received 86 cycles of chemotherapy, 36 by standard dosing and 50 by adaptive control. However, there was no demonstrable advantage to the adaptive control scheme, because of apparent bias of the previous model. A new model was proposed that also included serum albumin, performance status, and prior RBC transfusions as measures of interpatient pharmacodynamic variability. We conclude that adaptive control dosing of etoposide is feasible but that the therapy must be individualized for both pharmacokinetic and pharmacodynamic variability.

Algorithms↗

Parallel genetic basis for repeated evolution of armor loss in Alaskan threespine stickleback populations.

Most adaptation is thought to occur through the fixation of numerous alleles at many different loci. Consequently, the independent evolution of similar phenotypes is predicted to occur through different genetic mechanisms. The genetic basis of adaptation is still largely unknown, however, and it is unclear whether adaptation to new environments utilizes ubiquitous small-effect polygenic variation or large-effect alleles at a small number of loci. To address this question, we examined the genetic basis of bony armor loss in three freshwater populations of Alaskan threespine stickleback, Gasterosteus aculeatus, that evolved from fully armored anadromous populations in the last 14,000 years. Crosses between complete-armor and low-armor populations revealed that a single Mendelian factor governed the formation of all but the most anterior lateral plates, and another independently segregating factor largely determined pelvic armor. Genetic mapping localized the Mendelian genes to different chromosomal regions, and crosses among these same three widely separated populations showed that both bony plates and pelvic armor failed to fully complement, implicating the same Mendelian armor reduction genes. Thus, rapid and repeated armor loss in Alaskan stickleback populations appears to be occurring through the fixation of large-effect variants in the same genes.

Animals↗

Perceived control of recovery from physical disability: measurement and prediction.

Perceived personal control has been found to be predictive of desirable outcomes in a variety of health care settings. It was hypothesized that it would also explain some of the variance in adaptation to and coping with physical disability and would therefore be predictive of recovery. A Recovery Locus of Control scale (RLOC) was developed, independent judges agreeing on five internal and four external items. The scale was shown to have good internal consistency when used with adults recently disabled by a stroke or wrist fracture. Patients' RLOC was assessed at the start of rehabilitation and recovery from physical disability was monitored using measures appropriate for each clinical group. In both groups, greater internality was associated with faster recovery. Results are discussed with respect to the likely mediating factors and the role of health professionals in facilitating internality.

Adaptation, Psychological↗

Seasonal fluctuations in fitness result in severe reductions in effective population size.

Genetic evidence for fluctuating selection has begun to accumulate for different species over the past few decades, especially for the Drosophila genus where studies have reported hundreds of loci undergoing putatively adaptive oscillations across successive seasons. However, most theoretical and simulation studies of fluctuating selection have relied on abstract or weakly parameterized models, making it difficult to assess their relevance for natural populations. In this study, we simulate multilocus seasonally fluctuating selection under a recently developed model and examine its effect on the variance effective population size (Ne ) at a genome-wide scale. By recapitulating genomic, demographic, and evolutionary parameters from natural Drosophila populations in our simulations, we were able to reproduce allele frequency oscillations reported in recent studies and show that these lead to ~50% genome-wide reductions in Ne . We also demonstrate that Ne reductions are well predicted by the maximum frequency amplitude among all adaptively fluctuating loci, and that the frequency amplitudes are largely determined by the number of adaptively fluctuating loci and the strength of their epistatic interactions. Our results demonstrate that fluctuating selection can substantially reduce effective population size and underscore the importance of temporally variable selection in shaping genome-wide patterns of variation beyond classical models.

Drosophila melanogaster↗

Metabolic gene-deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes.

Genome-scale metabolic models have a promising ability to describe cellular phenotypes accurately. Here we show that strains of Escherichia coli carrying a deletion of a single metabolic gene increase their growth rates (by 87% on average) during adaptive evolution and that the endpoint growth rates can be predicted computationally in 39 of 50 (78%) strains tested. These results show that computational models can be used to predict the eventual effects of genetic modifications.

Directed Molecular Evolution↗

Distinguishing enzyme structures from non-enzymes without alignments.

The ability to predict protein function from structure is becoming increasingly important as the number of structures resolved is growing more rapidly than our capacity to study function. Current methods for predicting protein function are mostly reliant on identifying a similar protein of known function. For proteins that are highly dissimilar or are only similar to proteins also lacking functional annotations, these methods fail. Here, we show that protein function can be predicted as enzymatic or not without resorting to alignments. We describe 1178 high-resolution proteins in a structurally non-redundant subset of the Protein Data Bank using simple features such as secondary-structure content, amino acid propensities, surface properties and ligands. The subset is split into two functional groupings, enzymes and non-enzymes. We use the support vector machine-learning algorithm to develop models that are capable of assigning the protein class. Validation of the method shows that the function can be predicted to an accuracy of 77% using 52 features to describe each protein. An adaptive search of possible subsets of features produces a simplified model based on 36 features that predicts at an accuracy of 80%. We compare the method to sequence-based methods that also avoid calculating alignments and predict a recently released set of unrelated proteins. The most useful features for distinguishing enzymes from non-enzymes are secondary-structure content, amino acid frequencies, number of disulphide bonds and size of the largest cleft. This method is applicable to any structure as it does not require the identification of sequence or structural similarity to a protein of known function.

Algorithms↗

Synaptic plasticity in the mormyrid electrosensory lobe.

The mormyrid electrosensory lateral line lobe (ELL) is one of several different sensory structures in fish that behave as adaptive sensory processors. These structures generate negative images of predictable features in the sensory inflow which are added to the actual inflow to minimize the effects of predictable sensory features. The negative images are generated through a process of association between centrally originating predictive signals and sensory inputs from the periphery. In vitro studies in the mormyrid ELL show that pairing of parallel fiber input with Na+ spikes in postsynaptic cells results in synaptic depression at the parallel fiber synapses. The synaptic plasticity observed at the cellular level and the associative process of generating negative images of predicted sensory input at the systems level share a number of properties. Both are rapidly established, anti-Hebbian, reversible, input-specific and tightly restricted in time. These common properties argue strongly that associative depression at the parallel fiber synapse contributes to the adaptive generation of negative images in the mormyrid ELL.

Animals↗

Seasonal fluctuations in fitness result in severe reductions in effective population size.

Genetic evidence for fluctuating selection has begun to accumulate for different species over the past few decades, especially for the Drosophila genus where studies have reported hundreds of loci undergoing putatively adaptive oscillations across successive seasons. However, most theoretical and simulation studies of fluctuating selection have relied on abstract or weakly parameterized models, making it difficult to assess their relevance for natural populations. In this study, we simulate multilocus seasonally fluctuating selection acting on standing genetic variation under a recently developed model and examine its effect on the variance effective population size (Ne) at a genome-wide scale. By recapitulating genomic, demographic, and evolutionary parameters from natural Drosophila populations in our simulations, we were able to reproduce allele frequency oscillations reported in recent studies and show that these lead to ∼50% genome-wide reductions in Ne. We also demonstrate that Ne reductions are well predicted by the maximum frequency amplitude among all adaptively fluctuating loci, and that the frequency amplitudes are largely determined by the number of adaptively fluctuating loci and the strength of their epistatic interactions. Our results demonstrate that fluctuating selection can substantially reduce effective population size and underscore the importance of temporally variable selection in shaping genome-wide patterns of variation beyond classical models.

Drosophila melanogaster↗

Effect of muscle fatigue on internal model formation and retention during reaching with the arm.

The motor system adapts to novel dynamic environments by forming internal models that predict the muscle forces needed to move skillfully. The goal of this study was to determine how muscle fatigue affects internal model formation during arm movement and whether an internal model acquired while fatigued could be recalled accurately after rest. Twelve subjects adapted to a viscous force field applied by a lightweight robot as they reached to a target. They then reached while being resisted by elastic bands until they could no longer touch the target. This protocol reduced the strength of the muscles used to resist the force field by approximately 20%. The bands were removed, and subjects adapted again to the viscous force field. Their adaptive ability, quantified by the amount and time constant of adaptation, was not significantly impaired following fatigue. The subjects then rested, recovering approximately 70% of their lost force-generation ability. When they reached in the force field again, their prediction of the force field strength was different than in a nonfatigued state. This alteration was consistent with the use of a higher level of effort than normally used to counteract the force field. These results suggest that recovery from fatigue can affect recall of an internal model, even when the fatigue did not substantially affect the motor system's ability to form the model. Recovery from fatigue apparently affects recall because the motor system represents internal models as a mapping between effort and movement and relies on practice to recalibrate this mapping.

Adaptation, Physiological↗

What do we tell the children? Contrasting the disclosure choices of two HD families regarding risk status and predictive genetic testing.

Above all else, predictive genetic testing provides information. Gaining insight into the psychosocial effects of this information is a primary goal of genetic counseling. For individuals utilizing predictive genetic testing, the acquisition of genetic information requires choices regarding disclosure within the family. This study uses a phenomenological methodology to explore the contrasting choices of two sets of HD parents regarding the disclosure of genetic risk status to their children. Additionally, the children (now adults) discuss their lived experience growing up with contrasting disclosure dynamics, and their current views regarding the use of predictive genetic testing for themselves. The primary finding of this study is that all of the adult children now express preference for early disclosure of genetic risk and an open/supportive communication style regarding HD. This finding has value for clinicians working with HD families who must make decisions regarding disclosure issues related to predictive genetic testing.

Adaptation, Psychological↗