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PubMed2003

Adapting the Charlson Comorbidity Index for use in patients with ESRD.

BACKGROUND: Accurate prediction of survival for patients with end-stage renal disease (ESRD) and multiple comorbid conditions is difficult. In nondialysis patients, the Charlson Comorbidity Index has been used to adjust for comorbidity. The purpose of this study is to assess the validity of the Charlson index in incident dialysis patients and modify the index for use specifically in this patient population. METHODS: Subjects included all incident hemodialysis and peritoneal dialysis patients starting dialysis therapy between July 1, 1999, and November 30, 2000. These 237 patients formed a cohort from which new integer weights for Charlson comorbidities were derived using Cox proportional hazards modeling. Performance of the original Charlson index and the new ESRD comorbidity index were compared using Kaplan-Meier survival curves, change in likelihood ratio, and the c statistic. RESULTS: After multivariate analysis and conversion of hazard ratios to index weights, only 6 of the original 18 Charlson variables were assigned the same weight and 6 variables were assigned a weight higher than in the original Charlson index. Using Kaplan-Meier survival curves, we found that both the original Charlson index and the new ESRD comorbidity index were associated with and able to describe a wide range of survival. However, the new study-specific index had better validated performance, indicated by a greater change in the likelihood ratio test and higher c statistic. CONCLUSION: This study indicates that the original Charlson index is a valid tool to assess comorbidity and predict survival in patients with ESRD. However, our modified ESRD comorbidity index had slightly better performance characteristics in this population.

Aged↗
PubMed2004

Learning multiple visuomotor transformations: adaptation and context-dependent recall.

Recent motor control theories suggest that the brain uses internal models to plan and control accurate movements. An internal model is thought to represent how the biomechanics of the arm interacting with the outside world would respond to a motor command; therefore it can be seen as a predictive model of the reafference that helps the system plan ahead. Moreover, adaptation studies show that humans can learn multiple internal models. It is not clear, however, whether and how contextual cues are used to switch among competing internal models, which are required to compensate for altered environments. To investigate this question, we asked healthy participants to perform center-out pointing movements under normal and distorted visual feedback (0 degrees , 30 degrees counterclockwise, and 60 degrees clockwise rotation of hand-screen cursor relationships) conditions. The results suggest that humans can learn multiple environments simultaneously and can use contextual cues to facilitate adaptation and to recall the appropriate internal model of the visuomotor transformation.

Adaptation, Physiological↗
PubMed2003

Optimal foraging and predator-prey dynamics III.

In the previous two articles (Theor. Popul. Biol. 49 (1996) 265-290; 55 (1999) 111-126), the population dynamics resulting from a two-prey-one-predator system with adaptive predators was studied. In these articles, predators followed the predictions of optimal foraging theory. Analysis of that system was hindered by the incorporation of the logistic description of prey growth. In particular, because prey self-regulation dependence is a strong stabilizing mechanism, the effects of optimal foraging could not be easily separated from the effects of bottom-up control of prey growth on species coexistence. In this article, we analyze two models. The first model assumes the exponential growth of both prey types while the second model assumes the exponential growth of the preferred prey type and the logistic growth of the alternative prey type. This permits the effect of adaptive foraging on two-prey-predator food webs to be addressed. We show that optimal foraging reduces apparent competition between the two prey types, promotes species coexistence, and leads to multiple attractors.

Animals↗
PubMed1999

A population pharmacokinetic-pharmacodynamic analysis of repeated measures time-to-event pharmacodynamic responses: the antiemetic effect of ondansetron.

This paper presents and illustrates methodology for specifying, estimating, and evaluating a predictive model for repeated measures time-to-event responses. The illustrative example specifies a model of the antiemetic effect vs. concentration relationship for the 5-HT3 antagonist ondansetron in the human ipecac model for emesis. A key part of this model is a time-dependent log hazard function for emesis that is increased by ipecac administration and decreased by ondansetron concentration. The model is fit using an approximate maximum likelihood method. The data consist of the time free of emeses and, for those individuals with emetic episodes, the time(s) of the episode(s). Model evaluation is accomplished using residual plots adapted to time-to-event data and a "posterior predictive check" wherein observed data statistics are compared to those obtained from data simulated from the fitted model. The ondansetron concentration required to obtain a 50% reduction in the hazard of emesis is estimated to be 1.4 +/- 0.2 ng/ml, and the rate constant for elimination of ipecac-induced hazard is 1.5 +/- 0.2 hr-1.

Antiemetics↗
PubMed1987

Toward a predictive model of suicidal ideation and behavior: some preliminary data in college students.

Within a multivariate statistical design, the relationship of various interpersonal, emotional, and cognitive variables to suicidal ideation and behavior in college students was examined. A total of 158 subjects (58 males, 100 females) completed self-report measures of life stress, faulty cognitions, loneliness, depression, hopelessness, family cohesiveness, adaptive reasons for living, and suicidal ideation and behavior. The results of a multiple-regression analysis, forward-inclusion algorithm, indicated that a predictive equation consisting of loneliness, irrational beliefs, and low adaptive reasons for living best accounted for suicidal behavior scores. To determine the basic structures and power of the predictor variables under study, a factor analysis and composite regression were employed, resulting in a predictive equation consisting of three factors: Social/Emotional Alienation, Cognitive Distortions, and Deficient Adaptive Resources. Results are discussed in terms of an interactional model of suicidal behavior.

Adult↗
PubMed2004

Mutational pattern of influenza B viruses adapted to high growth replication in embryonated eggs.

Improved replication of influenza viruses in embryonated chicken eggs (CE) permits increased vaccine production and availability. We investigated the growth properties of influenza B viruses in relation to specific mutations occurring after serial passage in CE. In serial passage experiments yielding high growth variants of B/Victoria/504/2000, mutations predicted to alter amino acid (AA) composition occurred only near the receptor-binding pocket of the hemagglutinins (HA) and in no other genes. Two B/Victoria/504/2000 high growth variants had the same AA substitutions in HA (R162M and D196Y), but the higher yield variant had a third substitution (G141E), which also altered antigenic characteristics. In a serial passage experiment yielding a high growth variant of B/Hong Kong/330/2001, mutations predicted to alter AA composition occurred only in PB2 and NP in domains predicted to relate to RNP formation and function. Our results indicate that adaptation of influenza B viruses to high-yield replication by serial passage in CE requires few mutations either in internal or external genes. Specific modifications of genes or a combination of genes could be used to optimize or create influenza B viruses for specific growth substrates.

Adaptation, Biological↗
PubMed2004

Community capacity for adaptation to climate-induced water shortages: linking institutional complexity and local actors.

There is growing concern for the capacity of urban and rural communities to manage current water shortages and to prepare for shortages that may accompany predicted changes in climate. In this paper, concepts relating to the notion of climate adaptation and particularly "capacity building" are used to elucidate several determinants of community-level capacity for water management. These concepts and criteria are then used to interpret empirically derived insights relating to local management of water shortages in Ontario, Canada. General determinants of water-related community capacity relate to upper tier political and institutional arrangements; the characteristics of, and relationships among, pertinent agencies, groups, or individuals involved in water management; and the adequacy of financial, human, information, and technical resources. The case analysis illustrates how general factors play out in local experience. The findings point to geographically specific factors that influence the effectiveness of management. Key factors include collaboration between water managers, clarification of agency roles and responsibilities, integration of water management and land-use planning, and recognition and participation of both urban and rural stakeholders, whose sensitivities to water shortages are spatially and temporally variable.

Climate↗
PubMed1983

A model for prediction of resynchronization after time-zone flights.

Utilizing experimental data from three flight studies, a concept was developed which allows appraising average resynchronization for any day after arrival in a new time-zone. The course of adaptation is nonlinear and can be mathematically represented by an exponential function. The model predicts higher initial resynchronization rates when more time zones are crossed, but total time for complete reentrainment is essentially the same and, thus is independent of the number of time-zones. The equation derived from experimental data is converted into an e-function and the resulting time constants are presented as they evolved for different functions and flight directions.

Aerospace Medicine↗
PubMed2005

Quantifying effects of retinal illuminance on frequency doubling perimetry.

PURPOSE: To measure and quantify effects of variation in retinal illuminance on frequency doubling technology (FDT) perimetry. METHODS: A Zeiss-Humphrey/Welch Allyn FDT perimeter was used with the threshold N-30 strategy. Study 1, quantifying adaptation: 11 eyes of 11 subjects (24-46 years old) were tested with natural pupils, and then retested after stable pupillary dilation with neutral density filters of 0.0, 0.6, 1.2, and 1.6 log unit in front of the subject's eye. Study 2, predicting effect of reduced illuminance: 17 eyes of 17 subjects (26-61 years old) were tested with natural pupils, and then retested after stable pupillary miosis (assessed with an infrared camera). A quantitative adaptation model was fit to results of Study 1; the mean adaptation parameter was used to predict change in Study 2. RESULTS: Study 1: Mean defect (MD) decreased by 10 dB over a 1.6 log unit range of retinal illuminances; model fits for all subjects had r2> 95%. Study 2: Change in MD (DeltaMD) ranged from -7.3 dB to +0.8 dB. The mean adaptation parameter from Study 1 accounted for 69% of the variance in DeltaMD (P <0.0005), and accuracy of the model was independent of the magnitude of DeltaMD (r2< 1%, P >0.75). CONCLUSIONS: The results confirmed previous findings that FDT perimetry can be dramatically affected by variations in retinal illuminance. Application of a quantitative adaptation model provided guidelines for estimating effects of pupil diameter and lens density on FDT perimetry.

Adaptation, Ocular↗
PubMedDate not supplied

Comparison of reinforcement schedules in the reduction of stereotypy with supported routines.

The rates and durations of stereotypic behaviors in four adolescents with severe mental retardation were measured during two daily vocational training sessions and during contiguous periods of leisure in their special education classrooms. Vocational training was conducted in two different tasks, alternating across days. The task requirements for each participant were matched to each participant's learning and performance characteristics. The participants were exposed to a fixed ratio schedule of tokens exchangeable for food items on one task and to a variable interval schedule for the same consequences on the second task. The schedules were chosen as an initial test of a matching-law based prediction by Myerson and Hale (1984): Variable interval reinforcement for adaptive behavior will produce less allocation of responding to maladaptive behavior than will a ratio-based intervention. When work performances stabilized, the schedules of token delivery were reversed across the tasks and performances again stabilized. Results are reported for periods when work performances met stability criteria. Stereotypy occurred more during leisure than during vocational training under either schedule. The major differences in stereotypy between leisure and vocational training were differences in episode length rather than rate of onset. Onset of stereotypy in vocational training, however, occurred at higher rates under the interval schedule than under the ratio schedule in both tasks. The results are discussed in terms of Myerson and Hale's prediction and implications for further research and application.

Adolescent↗
PubMed2004

Effect of adaptation direction on the motion VEP and perceived speed of drifting gratings.

The N200 amplitude of the motion-onset VEP evoked by a parafoveal grating of variable contrast (0.5-64%), constant speed (2 degrees/s), direction (horizontally rightward), and spatial frequency (2 cpd) was studied before and after adaptation to a stationary or drifting grating (1, 2, or 4 degrees/s rightward or leftward). These results are compared to those for the pattern-appearance VEP. Psychophysical measurements were made simultaneously of the perceived speed. While iso-directional (rightward) adaptation leads to a mean amplitude reduction of 39%, the decrease after counter-directional adaptation has a size of 20%. The post-adaptation matches of perceived speed differ in dependence on the iso-directional adapting speed and decrease on average to 98%, 85%, and 69% of the pre-adapt perceived speed after 1, 2, and 4 degrees/s adapting speeds, respectively. The perceived speed is moderately reduced (83% of the pre-adapt value) after counter-directional adaptation nearly independently of the adapting speed. A model of velocity processing is presented, which enables us to predict the trends of the experimental motion VEP and perceived speed data.

Adaptation, Physiological↗
PubMed1990

Dynamic interactions between accommodation and convergence.

Frequency-domain equations were derived for the current dual-interaction model of accommodation and convergence control, and its adaptive behavior was related to the system's parameters. Contrary to predictions based on the steady-state performance of the model [18], dynamic analysis showed that the AC/A is sensitive to the method of measurement and a procedure is established for its reliable determination. Additionally, the results provided theoretical support for the empirical finding that low AC/A and CA/C ratios are associated with high accommodative and convergence adaptation, respectively [15]. The derived equations should help future studies relate the physiological behavior of accommodative and convergence to specific model parameters.

Accommodation, Ocular↗
PubMed2000

The longitudinal relationship of clinical symptoms, cognitive functioning, and adaptive life in geriatric schizophrenia.

Cognitive dysfunction is increasingly being recognized as a major contributor to the adaptive impairment seen in most patients with schizophrenia. Reported here is a prospective longitudinal evaluation of the relationship between cognitive and adaptive functioning in elderly patients with schizophrenia. It was hypothesized that baseline cognitive and negative, but not positive symptoms, would be predictive of cross-sectional impairment and longitudinal outcome. Subjects were 168 elderly patients with schizophrenia, free of major neurological disorders, who were residents of a long-term psychiatric facility. Subjects were assessed at baseline and again an average of 15months later. The PANSS was used to assess the severity of symptoms of schizophrenia. Cognitive symptoms were assessed using the components of the CERAD cognitive battery. Social and adaptive functioning was assessed using the SAFE scale. Spearman correlations were determined among clinical variables, and the rank ordering of prediction of SAFE scale scores at follow-up was determined using a stepwise regression procedure. At follow-up, adaptive life skills correlated with cognitive performance and negative symptoms (Spearman rho values 0. 41-0.57, all p values <0.0001), but not positive symptoms (r=0.09, n. s.). Among cognitive tasks, verbal learning and memory were most highly correlated with adaptive skills at follow-up. These results confirm and extend previous studies that indicate that cognitive impairments are predictive, both cross-sectionally and longitudinally, of adaptive life skills in persons with schizophrenia. Negative symptoms, but not positive symptoms, were correlated with impaired adaptive skills. Taken together, these results underscore the need to develop more effective treatments for cognitive and negative symptoms in schizophrenia.

Activities of Daily Living↗
PubMed1986

The somatosensory thalamus of the raccoon: properties of single neurons responsive to light mechanical stimulation of the forepaw.

These studies were undertaken to characterize the discharge properties of single neurons of the raccoon thalamic ventrobasal complex (VB) that respond to light mechanical stimulation of the glabrous surfaces of the forepaw. Microelectrodes were used to record the extracellular activity of 146 cells in anesthetized raccoons, and all neurons were histologically verified as falling within or along the boundaries of VB. Sixty-one neurons were tested for activation by electrical stimulaton of primarily somatosensory cortex. Of these, 88% were antidromically activated, 5% were synaptically activated, and the remaining 7% were unresponsive. Out of the total sample of 146 neurons, 136 had peripheral receptive fields (RFs) that were restricted to glabrous skin and revealed properties of modality and place-specificity predictable through knowledge of properties of primary mechanoreceptive afferents. Rapidly adapting (RA) neurons accounted for 77% of this modality-place-specific sample, while 19% were slowly adapting (SA), and 4% revealed properties indicative of input from Pacinian afferents (Pc). Absolute displacement thresholds were comparable for RA and SA neurons (range = 6-415 micron). Palmar RF areas (range = 3.3-328 mm2) were significantly larger than digital RF areas (range = 0.5-98.2 mm2). As defined by exponents (b) of power functions relating instantaneous discharge frequency to displacement ramp velocity, SA neurons formed a single, homogeneous group (range of values of b = 0.633-0.720). However, RA neurons fell into three distinct groups: those showing relatively steep functions (b = 0.559-0.938), those showing relatively flat functions (b = 0.146-0.334), and those showing discontinuous, or step, functions. A small number of neurons (7% of total sample) revealed "complex" properties, not predictable from knowledge of properties of primary afferents. These included five neurons whose RFs encompassed both glabrous and hairy skin, and several linear orientation, or "tactile edge," detectors. The present results, in conjunction with those of earlier studies of the raccoon dorsal column-medial lemniscal system, lead to the conclusion that different types of information transformation are emphasized at different levels of the system. Intramodality convergences (increases in RF area) occur primarily within the cuneothalamic relay, while changes in the coding of quantitative information are primarily a function of VB neurons. The appearance of linear orientation detectors--a type of tactile "feature detector"--indicates that the synthesis of information regarding complex spatial properties of stimuli has its beginnings within the somatosensory thalamus.

Animals↗
PubMed2007

Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine spot saliva samples II. Model application.

To develop and compare methods that predict individual nicotine (NIC) clearance, which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3'-hydroxycotinine (3HC) measurements. COT and 3HC saliva concentrations in smokers were simulated utilizing a mechanistic population pharmacokinetic model of NIC metabolism that was adapted from the one described in a companion paper. Four methods to predict NIC clearance using the metabolites concentrations were compared. The precision bias, and the fraction of predictions that are made with an absolute error below 25% were the performance measures evaluated. Four prediction methods were compared: (M1) reference method, an intercept slope model of the metabolite concentration ratios ([3HC]/[COT]) (M2) an intercept slope model of the natural logarithm of the metabolite ratios (M3) a spline of the logarithm of the metabolite ratios (M4) Maximal Posteriori Bayesian estimate of NIC clearance conditioned on the model, COT and 3HC concentrations. In addition, the effect of smoking patterns on the concentrations of COT and 3HC was evaluated. The precision, accuracy, and the fraction of predictions with an absolute error below 25%, were higher for methods M2-M4 compared to method M1. However, the differences between M2 and M4 were small. Additionally, smoking pattern did not affect the metabolite concentration profiles. Predicting NIC clearance using an intercept slope model of the natural logarithm of the ratio of 3HC to COT appears to be a relatively simple method that is better than using the metabolite ratio directly. This method has a bias of approximately -10%, precision of approximately 60%. The fraction of estimates below an absolute error of 25% is 43%. These results support use of M2 to estimate CYP2A6 activity in smokers in the clinical setting.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

[Factors predicting depression in hemodialysis patients].

PURPOSE: This study was done to provide fundamental data for developing a depression prediction model by discovering main factors that affect depression in patients who do maintenance hemodialysis. METHOD: The subjects were 191 patients doing maintenance hemodialysis selected from outpatient dialysis clinics at 9 major general hospitals, The Instrument tools utilized in this study were adapted from depression, fatigue, sleep disturbance, stress, adaptation,symptoms, daily activities, and role limitation and thoroughly modified to verify reliability and validity. The collected data was analyzed with a SPSS-PC 11.0 Window Statistics Program for real numbers, percentage, average, standard deviation, and multiple regression. RESULTS: The correlation factor for depression was (M=2.54) fatigue (M=3.12), sleep disturbance (M=2.82), stress (M=3.04), adaptation (M=2.53), daily activities (M=2.24), symptoms (M=2.37), and role limitation (M=2.24). The strongest factor that affected depression was explained by symptoms of the patients who performed hemodialysis. The analysis of the factors that affected depression revealed a 58.4% prediction in symptoms, stress, role limitation, and adaptation. CONCLUSION: It has been confirmed that the regression equation model (Depression=7.351 + .266*symptoms + .260*stress -.189*adaptation + .057*fatigue) of this research may serve as a prediction factor for depression in Hemodialysis Patients.

Adult↗
PubMed2001

How closely correlated are molecular and quantitative measures of genetic variation? A meta-analysis.

The ability of populations to undergo adaptive evolution depends on the presence of quantitative genetic variation for ecologically important traits. Although molecular measures are widely used as surrogates for quantitative genetic variation, there is controversy about the strength of the relationship between the two. To resolve this issue, we carried out a meta-analysis based on 71 datasets. The mean correlation between molecular and quantitative measures of genetic variation was weak (r = 0.217). Furthermore, there was no significant relationship between the two measures for life-history traits (r = -0.11) or for the quantitative measure generally considered as the best indicator of adaptive potential, heritability (r = -0.08). Consequently, molecular measures of genetic diversity have only a very limited ability to predict quantitative genetic variability. When information about a population's short-term evolutionary potential or estimates of local adaptation and population divergence are required, quantitative genetic variation should be measured directly.

Animals↗