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PubMed1997

Adults with mental retardation as supports to their parents: effects on parental caregiving appraisal.

This study was conducted to determine whether support provided to caregivers by their adult children with mental retardation would influence caregiving appraisals. We also examined how severity of disability of the adult child, personal and social resources of the caregiver, and amount of caregiver assistance to the adult with mental retardation influenced caregiving appraisals. Using surveys and interviews we collected information from 80 primary caregivers on caregiving burden and satisfaction and six predictors of burden and satisfaction. Findings indicate that greater support from the adult child to the caregiver resulted in greater satisfaction and less burden. Adaptive and maladaptive behaviors and caregiving assistance all predicted caregiving satisfaction but only maladaptive behaviors predicted caregiving burden.

Adult↗
PubMedDate not supplied

Free-energy analysis of enzyme-inhibitor binding: aspartic proteinase-pepstatin complexes.

Expeditious in silico determinations of the free energies of binding of a series of inhibitors to an enzyme are of immense practical value in structure-based drug design efforts. Some recent advances in the field of computational chemistry have rendered a rigorous thermodynamic treatment of biologic molecules feasible, starting from a molecular description of the biomolecule, solvent, and salt. Pursuing the goal of developing and making available a software for assessing binding affinities, we present here a computationally rapid, albeit elaborate, methodology to estimate and analyze the molecular thermodynamics of enzyme-inhibitor binding with crystal structures as the point of departure. The complexes of aspartic proteinases with seven inhibitors have been adopted for this study. The standard free energy of complexation is considered in terms of a thermodynamic cycle of six distinct steps decomposed into a total of 18 well-defined components. The model we employed involves explicit all-atom accounts of the energetics of electrostatic interactions, solvent screening effects, van der Waals components, and cavitation effects of solvation combined with a Debye-Huckel treatment of salt effects. The magnitudes and signs of the various components are estimated using the AMBER parm94 force field, generalized Born theory, and solvent accessibility measures. Estimates of translational and rotational entropy losses on complexation as well as corresponding changes in the vibrational and configurational entropy are also included. The calculated standard free energies of binding at this stage are within an order of magnitude of the observed inhibition constants and necessitate further improvements in the computational protocols to enable quantitative predictions. Some areas such as inclusion of structural adaptation effects, incorporation of site-dependent amino acid pKa shifts, consideration of the dynamics of the active site for fine-tuning the methodology are easily envisioned. The present series of studies, nonetheless, creates potentially useful qualitative information for design purposes on what factors favor protein-drug binding. The net binding free energies are a result of several competing contributions with 6 of the 18 terms favoring complexation. The nonelectrostatic contributions (i.e., the net van der Waals interactions) and the differential cavitation effects favor binding. Electrostatic contributions show considerable diversity and turn out to be favorable in a consensus view for the seven aspartic proteinase-inhibitor complexes examined here. Implications of these observations to drug design are discussed.

Aspartic Acid Endopeptidases↗
PubMed2001

Skeletal advancement for the treatment of obstructive sleep apnea in children.

OBJECTIVE: Maxillomandibular advancement is curative for some adult patients with obstructive sleep apnea (OSA). Little is known, however, about the efficacy of this treatment in children. The purpose of this retrospective analysis is to assess the clinical outcomes of children with medically refractory OSA who were treated with a variety of procedures to advance the maxillofacial skeleton. METHODS: The records of eight children with OSA (five boys and three girls; mean age, 8.6 years; range, 2 to 17 years) were reviewed. Six children had identifiable syndromes associated with micrognathia, one child had mandibular ankylosis, and one child was nonsyndromic. In five of the children, conventional medical and surgical treatment of OSA had failed; therefore, these children were considered tracheostomy candidates. The remaining three children had had tracheostomies placed in infancy. Specific signs and symptoms with regard to each patient's OSA were identified and recorded. Bronchoscopy was performed preoperatively to evaluate the airway and localize the site of obstruction and again postoperatively if the patient's signs and symptoms recurred. Oxygen saturation and sleep patterns were monitored overnight in the five patients without tracheostomies, revealing a mean apnea index of 25.3 (range, 2.0 to 60.0) and mean lowest desaturation of 73% (range, 62% to 77%). All patients underwent a variety of skeletal procedures to advance the mandible, maxilla, and/or chin. OUTCOME MEASURES: Criteria for success after treatment were twofold: (1) decannulation and (2) cessation or improvement in symptoms facilitating avoidance of tracheostomy. Criteria for failure, likewise, were (1) inability to decannulate and (2) recurrence or nonimprovement in symptoms necessitating tracheostomy. RESULTS: To date, with a mean follow-up time of 7.2 years (range, 19 months to 19 years), the treatment of four of the eight children in our population can be considered a success. Two of the three children with previously placed tracheostomies were able to be decannulated within days of surgery and experienced no further signs or symptoms of OSA. Two other children experienced complete cessation of clinical signs and symptoms and elimination of previous oxygen requirements. Of the four patients in whom treatment failed, three had transient improvement (mean, 6 months) and, despite skeletal stability, eventually experienced relapse of symptoms: one patient with Down syndrome and tracheobronchomalacia required subsequent tracheostomy; the second had a central obstructive component and underwent a ventriculoperitoneal shunt for treatment of a Chiara I malformation; and the third experienced relapse of symptoms due to lack of mandibular growth. The fourth child could not be decannulated because of accompanying tracheal and laryngeal malacia. CONCLUSIONS: Skeletal advancement can be an effective treatment for medically refractory OSA in children. Success, however, is dependent not only on skeletal position but also on neuromuscular adaptation. Bronchoscopy is the most valuable diagnostic and predictive tool.

Adolescent↗
PubMed2003

Design and peptide-based validation of phage display antibodies for proteomic biochips.

To validate potential application of phage display-antibody arrays for high-throughput screening on a novel proteomics biochip, we examined the epitopes versus the full protein of glucose-6-phosphate-dehydrogenase (G6PD) from yeast. In a predictive approach, we used the Hopp-Woods method and compared the results with antibodies directed against the entire enzyme. In total, 16 peptides of a length of 11 amino acids each fulfilling the desired criteria were identified and synthesized. Subsequently, antibodies against G6PD were raised using a phage display library. Selective interaction of the antibodies with certain peptides facilitated the identification of epitopes predicted by the hydropathic profile. The setup was adapted to a novel biochip system based on surface-enhanced absorption for direct CCD-camera based screening.

Amino Acid Sequence↗
PubMed2003

[Abdominal and digestive manifestations in systemic vasculitides].

Digestive involvement is frequent during the course of systemic small and medium-sized vessel vasculitides. Clinical manifestations range from rapidly regressive abdominal pain to surgical manifestations associated with poor prognosis. These are usually associated with extra-abdominal signs, reflecting vasculitis activity. Isolated gastrointestinal involvement is observed in only 16% of these patients. The main clinical manifestations are common to all vasculitides (ischemia, bowel infarction and perforations, gastrointestinal hemorrhage due to mucosal ulcerations or aneurysmal ruptures), but some are more specific to one type (granulomatous ileo-colitis during Wegener's granulomatosis, eosinophilic colitis during Churg-Strauss syndrome). Gastrointestinal arteriography can be helpful for diagnosis, but has no prognostic value, likewise for the presence of ANCA. As there are no identified factors predictive of a surgical abdomen, therapy must be adapted individually, using steroids and immunosuppressive agents, generally cyclophosphamide. Prompt surgical and medical care of these seriously ill patients has lowered mortality from nearly 100% twenty years ago to approximately 23 to 56% currently.

Gastrointestinal Diseases↗
PubMed1992

Drug delivery optimization through Bayesian networks.

This paper describes how Bayesian Networks can be used in combination with compartmental models to plan Recombinant Human Erythropoietin (r-HuEPO) delivery in the treatment of anemia of chronic uremic patients. Past measurements of hematocrit or hemoglobin concentration in a patient during the therapy can be exploited to adjust the parameters of a compartmental model of the erythropoiesis. This adaptive process allows more accurate patient-specific predictions, and hence a more rational dosage planning. We describe a drug delivery optimization protocol, based on our approach. Some results obtained on real data are presented.

Anemia↗
PubMed1984

Physiological studies of exocrine pancreatic secretion in conscious rats. 6th communication: steady-state adaptation to different food composition.

In conscious rats provided with appropriate indwelling catheters the steady-state adaptation of digestive enzymes in pancreatic juice is investigated in relation to different food composition. Six isocaloric diets with different composition of carbohydrates (5-70%), proteins (10-57%) and fat (0-38%) are applied for two weeks before operation and also afterwards. The parameters determined are: flow-rate and total protein concentration of pancreatic juice, enzyme-separation by PAA-Gel-Electrophoresis and quantitative analysis of amylases I and II, lipase, chymotrypsins I and II and trypsin. The specific enzymatic activity, characterized by the enzyme fraction in per cent of total protein can be described best as a linear function of the corresponding nutrient portion (%) in the food. (Coefficient of linear regression mostly r = 0.98%). The regression lines for the sum of both amylases and all proteases are parallel to each other (y = 0.45x + b). Lipase activity is also linearly increasing with fat in food having a much smaller slope (y = 0.16x + b). The regression lines (y = ax + b) intersect with the ordinate at different points (section b), characterizing the "basal" secretion of pancreatic enzymes without any substrate in food. b (in %) for amylase I = 3.14, amylase II = 0.7 !, total proteases = 12.5 and lipase = 13.6. The regularity of inherent laws governing adaptation of pancreatic enzyme production and secretion to food composition allow to predict the prospective enzymatic secretion pattern for any given food composition.

Adaptation, Physiological↗
PubMed1983

Neuropsychology of alcoholism. Etiology, phenomenology, process, and outcome.

A number of empirical and conceptual issues are addressed in an effort to explain the diversity of neuropsychological deficits demonstrated by chronic alcoholics. In addition to consumption characteristics and the neurotoxic effects of ethanol, evidence is marshalled to implicate nutritional deficiency, hepatic disease, congeners in the beverage, and cognitive regression as also being contributory to the manifest impairments. Moreover, predrinking disturbances are considered that may be responsible in part for the neuropsychological deficits observed in chronic alcoholics. Our understanding of the neuropsychological concomitants of alcoholism can be increased by the adoption of a life-span approach to alcohol effects, localizing the system or region of maximal cerebral damage and relating these findings to treatment intervention. The extent to which adaptive capacity in alcoholics and social drinkers is predicted by neuropsychological test performance is of utmost importance, especially since nonalcoholic social drinkers also demonstrate a number of impairments.

Alcoholism↗
PubMed1993

Acceptance of full dentures.

The wearing of even technically perfect full dentures is associated with a significant deterioration of most, if not all, oral functions. The fact that between 85 and 90 per cent of patients receiving new and technically well made dentures and between 65 and 75 per cent of patients with older dentures are generally satisfied with the treatment result is therefore more of a tribute to human adaptation than to prosthodontic skill. Research has shown that variables claimed to play an important role in patient acceptance of full dentures, such as the quality of the dentures, the oral condition, the patient-dentist relationship, the patients' attitude toward dentures, the patients' personality, socio-economic factors, demographic variables, previous denture experience and oral stereognosis, have in fact no or negligible effects in this respect. Nor has the degree of prediction been appreciably improved by combining the effects of such variables. Variables of theoretical importance for acceptance of dentures such as the patients' motory ability and the quality and quantity of saliva have still to be studied. At the present time research has yet failed to furnish the clinician with a practical method whereby patients who are unlikely to accept full dentures can be identified with any degree of certainty. The clinician has therefore still no option but to base his prediction on an individual estimate of his patient's adaptive ability.

Adaptation, Psychological↗
PubMed1993

Psychosocial stress as a cause of infertility.

An adaptive model for the evolution of reproductive failure predicted psychosocial stress to increase as anatomic causes of infertility decrease. The nonanatomic infertility group in our study reported greater psychosocial stress than intermediate (P < 0.008) or anatomic groups (P < 0.0005). Controls, women with nonanatomic etiologies who were not attempting pregnancy, also reported higher psychosocial stress than the anatomic group (P < 0.007). Results are consistent with the hypothesis that psychosocial distress contributes significantly to the etiology of some forms of infertility.

Adult↗
PubMed1982

Psychological and physiological factors predicting the outcome on home hemodialysis.

As part of a study of "Adaptation to home dialysis" we have examined psychological, physiological, and social factors influencing the success of 136 patients on home hemodialysis, followed for greater than 18 months. The study has demonstrated specific physical, psychological, and stress factors associated with increased probability of failure on home hemodialysis. In those under 45 years of age, the profile of failure is of higher diastolic blood pressure in training, more frequent episodes of congestive heart failure, higher levels of stress associated with varying health and loss of sleep and greater anxiety and depression. In the older age group failure was associated with higher levels of depression and self depreciation, and higher levels of stress associated with fear of death, pain during dialysis and blood clotting. On the other hand, higher denial levels were positively correlated with success. There were no significant differences between profiles of those patients who succeeded and those who died. Although analysis is based on a retrospective study, the time sequence between data collection and end points suggests that patient profiling can be used in a predictive manner. The study emphasizes the importance of psychological and social factor analysis in the overall management of the patient with renal failure.

Adult↗
PubMed2003

Thermal adaptation in Drosophila serrata under conditions linked to its southern border: unexpected patterns from laboratory selection suggest limited evolutionary potential.

To investigate the ability of Drosophila serrata to adapt to thermal conditions over winter at the species southern border, replicate lines from three source locations were held as discrete generations over three years at either 19 degrees C (40 generations) or temperatures fluctuating between 7 degrees C and 18 degrees C (20 generations). Populations in the fluctuating environment were maintained either with an adult 0 degrees C cold shock or without a shock. These conditions were expected to result in temperature-specific directional selection for increased viability and productivity under both temperature regimes, and reduced development time under the fluctuating-temperature regime. Selection responses of all lines were tested under both temperature regimes after controlling for carry-over effects by rearing lines in these environments for two generations. When tested in the 19 degrees C environment, lines evolving at 19 degrees C showed a faster development time and a lower productivity relative to the other lines, while cold shock reduced development time and productivity of all lines. When tested in the fluctuating environment, productivity of the 7-18 degrees C lines selected with a cold shock was relatively lower than that of lines selected without a shock, but this pattern was not observed in the other populations. Viability and body size as measured by wing length were not altered by selection or cold shock, although there were consistent effects of source population on wing length. These results provide little evidence for temperature-specific adaptation in D. serrata-although the lines had diverged for some traits, these changes were not consistent with a priori predictions. In particular, there was no evidence for life-history changes reflecting adaptation to winter conditions at the southern border. The potential for D. serrata to adapt to winter conditions may therefore be limited.

Adaptation, Physiological↗
PubMed2006

A novel, model-based insulin and nutrition delivery controller for glycemic regulation in critically ill patients.

BACKGROUND: Critically ill patients are often hyperglycemic and insulin resistant, as well as highly dynamic. Tight glucose control has been shown to significantly reduce mortality in critical care. A physiological model of the glucose-insulin regulatory system is improved and used to develop an adaptive control protocol utilizing both nutritional and insulin inputs to control hyperglycemia. The approach is clinically verified in a critical care patient cohort. METHODS: A simple two-compartment model for glucose rate of appearance in plasma due to stepwise enteral glucose fluxes is developed and incorporated into a previously validated system model. A control protocol modulating intravenous insulin infusion and bolus, with an enteral feed rate, is developed, enabling tight and predictive glycemic regulation to preset targets. The control protocol is adaptive to patient time-variant effective insulin resistance. The model and protocol are verified in seven 10-h and one 24-h proof-of-concept clinical trials. Ethics approval was granted by the Canterbury Ethics Committee. RESULTS: Insulin requirements varied widely following acute changes in patient physiology. The algorithm developed successfully adapted to patient metabolic status and insulin sensitivity, achieving an average target acquisition error of 9.3% with 90.7% of all targets achieved within +/-20%. Prediction errors may not be distinguishable from sensor measurement errors. Large errors (>20%) are attributable to highly dynamic and unpredictable changes in patient condition. CONCLUSIONS: Tight, targeted stepwise regulation was exhibited in all trials. Overall, tight glycemic regulation is achieved in a broad critical care cohort with optimized insulin and nutrition delivery, effectively managing glycemia even with high effective insulin resistance.

Aged↗
PubMed2006

After prostate cancer: predictors of well-being among long-term prostate cancer survivors.

BACKGROUND: Despite growing numbers of prostate cancer (PCa) survivors, to the authors' knowledge there is little research regarding how personality, coping, and treatment influence men's psychologic well-being, as distinct from the often-studied functional, health-related quality of life. The purpose of this study was to examine how hope, optimism, use of coping strategies, and primary treatment predict well-being, positive and negative affect, impact, depression, and adaptive changes among PCa survivors. METHODS: A questionnaire tapping personality, primary treatment, and coping strategy predictor variables and outcome variables of both positive and negative aspects of well-being was sent to 1-8-year PCa survivors. The final sample included 490 men. RESULTS: Basic univariate analyses demonstrated that the men reported being happy, hopeful, and positive, with low levels of negative outcomes. Regression analyses demonstrated that positive outcomes were influenced primarily by personality. Negative outcomes were found to be affected by both personality and coping strategies. Adaptive changes were the only ones found to be significantly affected by primary treatment. CONCLUSIONS: Although longer-term survivorship of PCa does not appear to be a highly traumatic experience, personality factors and the use of coping strategies years after treatment were found to introduce variability to well-being in complex ways, differing in relation to positive and negative outcomes. Clinical attention should be given to how the experience of cancer fits within the larger context of an individual's attitudes, choices, and coping strategy orientation. Cancer 2006. (c) 2006 American Cancer Society.

Adaptation, Psychological↗
PubMed1994

A prospective study of family environments of children hospitalized for nonorganic failure-to-thrive.

Family functioning of nonorganic failure-to-thrive (NOFT) infants was compared with that of physically healthy, normally growing infants of similar socioeconomic status shortly after the time of the diagnosis of this condition (average age of 5 months) and again at 4 years of age. Families of NOFT infants demonstrated less adaptive relationships than did comparison-group infants, as measured by the Family Relationships Inventory (FRI) at both time points, but a comparable number of changes in residence and constellation on follow-up. Contrary to prediction, the quality of family relationships at point of diagnosis did not predict subsequent family relationships, residence, or constellation changes in the NOFT sample. However, more adaptive family relationships in the comparison group at study entry predicted fewer residence and constellation changes and more cohesive relationships 3 years later. The impact of significant discontinuities in family functioning and status should be considered in research and in clinical interventions with NOFT children.

Child, Preschool↗
PubMed1998

Local velocity representation: evidence from motion adaptation.

Adaptation to a moving visual pattern induces shifts in the perceived motion of subsequently viewed moving patterns. Explanations of such effects are typically based on adaptation-induced sensitivity changes in spatio-temporal frequency tuned mechanisms (STFMs). An alternative hypothesis is that adaptation occurs in mechanisms that independently encode direction and speed (DSMs). Yet a third possibility is that adaptation occurs in mechanisms that encode 2D pattern velocity (VMs). We performed a series of psychophysical experiments to examine predictions made by each of the three hypotheses. The results indicate that: (1) adaptation-induced shifts are relatively independent of spatial pattern of both adapting and test stimuli; (2) the shift in perceived direction of motion of a plaid stimulus after adaptation to a grating indicates a shift in the motion of the plaid pattern, and not a shift in the motion of the plaid components; and (3) the 2D pattern of shift in perceived velocity radiates away from the adaptation velocity, and is inseparable in speed and direction of motion. Taken together, these results are most consistent with the VM adaptation hypothesis.

Adaptation, Ocular↗
PubMedDate not supplied

Adapting genetic regulatory models by genetic programming.

In this paper, we focus on the task of adapting genetic regulatory models based on gene expression data from microarrays. Our approach aims at automatic revision of qualitative regulatory models to improve their fit to expression data. We describe a type of regulatory model designed for this purpose, a method for predicting the quality of such models, and a method for adapting the models by means of genetic programming. We also report experimental results highlighting the ability of the methods to infer models on a number of artificial data sets. In closing, we contrast our results with those of alternative methods, after which we give some suggestions for future work.

Algorithms↗
PubMed2001

A measure for predicting audibility discrimination thresholds for spectral envelope distortions in vowel sounds.

Both in speech synthesis and in sound coding it is often beneficial to have a measure that predicts whether, and to what extent, two sounds are different. This paper addresses the problem of estimating the perceptual effects of small modifications to the spectral envelope of a harmonic sound. A recently proposed auditory model is investigated that transforms the physical spectrum into a pattern of specific loudness as a function of critical band rate. A distance measure based on the concept of partial loudness is presented, which treats detectability in terms of a partial loudness threshold. This approach is adapted to the problem of estimating discrimination thresholds related to modifications of the spectral envelope of synthetic vowels. Data obtained from subjective listening tests using a representative set of stimuli in a 3IFC adaptive procedure show that the model makes reasonably good predictions of the discrimination threshold. Systematic deviations from the predicted thresholds may be related to individual differences in auditory filter selectivity. The partial loudness measure is compared with previously proposed distance measures such as the Euclidean distance between excitation patterns and between specific loudness applied to the same experimental data. An objective test measure shows that the partial loudness measure and the Euclidean distance of the excitation patterns are equally appropriate as distance measures for predicting audibility thresholds. The Euclidean distance between specific loudness is worse in performance compared with the other two.

Auditory Threshold↗