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Competent kids: children and adolescents with a chronic illness.

The social and personal competence of children and adolescents with a seizure disorder or an orthopaedic condition was assessed by parents and teachers. The contributions to these assessments of characteristics of the child, the intensity of the illness, and the child's temperament were explored using a hierarchical regression model. Parents and teachers rated all children as functioning fairly well. Children with a seizure disorder were perceived as significantly less competent than were their healthy peers (P less than 0.05). Across health status groups, children received higher competence scores from their parents than they did from their teachers (P less than 0.05). Competence scores did not differ according to the age of the child. The patterns of variables that predicted ratings of competence differed according to illness type and rater. Indicators of illness intensity explained a larger share of the variance in competence ratings for children with a seizure disorder (25%) than for children with an orthopaedic condition (5%). For children in this latter group, temperament explained a much larger proportion of the variance in both parents' (29%) and teachers' (42%) ratings of competence than did the illness intensity variables.

Adolescent↗

A conservative domain shared by HIV gp120 and EIAV gp90: implications for HIV vaccine design.

Both HIV and EIAV belong to the retroviridae family and lentivirus genus. Two variable regions (V3 and V4) of equine infectious anemia virus (EIAV) gp90 and two variable regions (V1 and V2) of HIV gp120 possibly adopt the same topology. We have studied the N-glycosylation properties and B cell linear epitope distribution profile of these two regions. Our results indicated that V3 and V4 of EIAV gp90 are very similar to V1 and V2 of HIV gp120. The differences between EIAV virulent and vaccine strains are mainly located at these two regions. Vaccine strains lose two N-glycosylation sites at these two regions. Because of the conservative domain shared by EIAV gp90 and HIV gp120, V1 and V2 of HIV gp120 and their glycosylation properties should be the regions preferably considered for HIV vaccine design.

AIDS Vaccines↗

Performance of US teaching hospitals: a panel analysis of cost inefficiency.

This research summarizes an analysis of the impact of environment pressures on hospital inefficiency during the period 1990-1999. The panel design included 616 hospitals. Of these, 211 were academic medical centers and 415 were hospitals with smaller teaching programs. The primary sources of data were the American Hospital Association's Annual Survey of Hospitals and Medicare Cost Reports. Hospital inefficiency was estimated by a regression technique called stochastic frontier analysis. This technique estimates a "best practice cost frontier" for each hospital that is based on the hospital's outputs and input prices. The cost efficiency of each hospital was defined as the ratio of the stochastic frontier total costs to observed total costs. Average inefficiency declined from 14.35% in 1990 to 11.42% in 1998. It increased to 11.78% in 1999. Decreases in inefficiency were associated with the HMO penetration rate and time. Increases in inefficiency were associated with for-profit ownership status and Medicare share of admissions. The implementation of the provisions of the Balanced Budget Act of 1997 was followed by a small decrease in average hospital inefficiency. Analysis found that the SFA results were moderately sensitive to the specification of the teaching output variable. Thus, although the SFA technique can be useful for detecting differences in inefficiency between groups of hospitals (i.e., those with high versus those with low Medicare shares or for-profit versus not-for-profit hospitals), its relatively low precision indicates it should not be used for exact estimates of the magnitude of differences associated with inefficiency-effects variables.

Cost-Benefit Analysis↗

The three-dimensional profile method using residue preference as a continuous function of residue environment.

In the 3-dimensional profile method, the compatibility of an amino acid sequence for a given protein structure is scored as the sum of the preferences of the residues for their environments in the 3D structure. In the original method (Bowie JU, Lüthy R, Eisenberg D, 1991, Science 253:164-170), residue environments were quantized into 18 discrete environmental classes. Here, amino acid residue preferences are expressed as a continuous function of environmental variables (residue area buried and fractional area buried by polar atoms). This continuous representation of residue preferences, expressed as a Fourier series, avoids the abrupt change of preference of residues in slightly different environments, as encountered in the original method with its 18 discrete environmental classes. When compared with the discrete 18-class representation of residue environments, this continuous 3D profile is found to be more sensitive in identifying sequences that fold into the profiled structure but share with it little sequence identity. The continuous 3D profile is also less sensitive to errors in environmental variables than is the discrete 3D profile. The continuous 3D profile can also be used to detect wrong folds or incorrectly modeled segments in an otherwise correct structure, as could the discrete 3D profile (Lüthy R, Bowie JU, Eisenberg D, 1992, Nature 356:83-85). Moreover, the progress of structure improvement during atomic refinement can also be monitored by examining the profile scores in a moving-window scan. Finally, by defining a functional form for profile scores, we open the way to profile atomic refinement in which an atomic structure adjusts to produce residue environments more compatible with the protein side chains.

Amino Acids↗

The effect of donor body mass index on primary graft nonfunction, retransplantation rate, and early graft and patient survival after liver transplantation.

Previous studies have suggested that moderate donor liver steatosis is associated with an increased incidence of primary graft nonfunction (PGNF), delayed graft function, early graft loss, and retransplantation rates. The objective of our study was to determine the effect of donor body mass index (dBMI), after adjusting for other known confounding variables, on PGNF, early graft failure, retransplantation rate, and patient survival. The United Network for Organ Sharing (UNOS) database (1987 to 2001) of 22,303 adult patients, excluding patients of pediatric age (age less than 18 years) and those with multiple organ transplantations, living donors, and retransplantations, was used for this study. Based on the BMI (kg/m(2)) of the organ donor, transplant recipients were divided into four groups as follows: BMI < 25 (group 1, n = 11,660), 25 to 29.9 (group 2, n = 7418), 30 to 34.9 (group 3, n = 2301), and > or = 35 (group 4, n = 924). Information on donor liver histology was available for 1603 patients who underwent transplantation after 1999, and this subgroup was divided into three groups based on severity of steatosis (group A, < 20%; group B, 20% to 35%; group C, > 35%). Incidence of PGNF and early retransplantation rates were similar in groups 1 to 4 and in groups A, B, and C. Logistic regression analysis showed that dBMI or severity of steatosis was not a predictor of PGNF and early retransplantation. Cox regression analysis, after adjusting for confounding variables, showed similar patient and graft survival at 1 month and 1, 2, and 5 years for groups 1 to 4, and at 1 month and 6 months for groups A, B, and C. Severe donor obesity or moderate steatosis did not influence short-term and long-term outcome of liver transplantation.

Adult↗

Comparison between subjective feelings to alcohol and nitrogen narcosis: a pilot study.

Nitrogen narcosis is often compared to alcohol intoxication, but no actual studies have been carried out in humans to test the comparability of these effects. If a common mechanism of action is responsible for the behavioral effects of these substances, biological variability of response to alcohol should correlate to that of nitrogen in the same individual. To test this hypothesis, subjective feelings were assessed in two separate occasions in 14 adult male, healthy volunteers, nonprofessional divers. In one occasion, each subject received 0.75 ml/kg (0.60 g/kg) alcohol 50% (v/v PO) and in another day underwent a simulated dive at 50 m for 30 min in a hyperbaric chamber. There was a significant correlation between reported feelings in the two sessions; subjects who felt less intoxicated after drinking also felt less nitrogen narcosis during the simulated dive. The results, although preliminary, raise the hypothesis that ethanol and nitrogen may share the same mechanisms of action in the brain and that biological differences might account for interindividual variability of responses to both ethanol and nitrogen.

Adult↗

Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora.

The glutamate-gated chloride channels (GluCls) are members of the ligand-gated ion channel superfamily that are thought to be involved in the mode of action of ivermectin and mechanism of resistance. Using reverse-transcriptase PCR techniques, 2 full-length GluCl cDNAs, encoding GluClalpha3 and GluClbeta subunits, were cloned from Cooperia oncophora, a nematode parasite of cattle. The two sequences show a high degree of identity to similar subunits from other nematodes. The C. oncophora GluClalpha3 subunit is most closely related to the Haemonchus contortus GluClalpha3B subunit, while C. oncophora GluClbeta subunit shares high sequence identity with the H. contortus GluClbeta subunit. Using single-strand conformation polymorphism, the genetic variability of these two genes was analysed in an ivermectin-susceptible isolate and an ivermectin-resistant field isolate of C. oncophora. Statistical analysis suggested an association between the C. oncophora GluClalpha3 gene and ivermectin resistance. No such association was seen with the GluClbeta gene.

Amino Acid Sequence↗

Correlates of hepatitis C virus infection in homeless men: a latent variable approach.

Homeless individuals are at risk for numerous health problems including Hepatitis C virus (HCV). HCV is primarily caused by sharing of equipment associated with injection drug use (IDU). In the current study, we assessed differences among HCV-negative and HCV-positive homeless men residing in Los Angeles (N = 198; about 50% HCV positive) on a number of risk factors and behaviors. Findings revealed several significant correlates of HCV-positive status. HCV-positivity was significantly and positively associated with a history of substance use (IDU and non-IDU), recent IDU-related behaviors including equipment sharing, other forms of sharing (e.g., toothbrushes, razors), homelessness severity, tattoos, sexually transmitted diseases, a jail/prison history, and greater age. Lifetime alcohol problems were not associated with HCV. Although associations of HCV with current IDU-related behaviors are not surprising, it is alarming that these behaviors were recent. Those who work among homeless populations should be aware not only of the high likelihood of HCV infection in this population but also of the transmission risk due to continued IDU sharing behaviors. Substance abuse treatment should be implemented to hinder the spread of HCV in this vulnerable population. Also, needle exchange and provision of clean ancillary IDU equipment should be encouraged in areas where homeless people are known to congregate.

Adolescent↗

Relationship of depressive symptoms to hypertension in a household survey in Harlem.

OBJECTIVE: Two possible explanations for an hypothesized association between depression and hypertension were examined: (1) shared stress-related risk factors are associated with both depression and hypertension and (2) life-style factors associated with depression lead to hypertension. METHODS: A predominantly black sample of 695 adults were interviewed in the Harlem Household Survey. Two measures of hypertension were used and compared-1) self-report and 2) elevated blood pressure (above 140/90 mm Hg)-on the basis of the mean of two blood pressure measures. Depressive symptoms were measured by use of a 24-item scale based on the Diagnostic Interview Schedule. Logistic regression models were used to test associations between hypertension and depressive symptoms, stressors, and life-style factors. RESULTS: Depressive symptoms were associated with self-reported hypertension but not with elevated blood pressure. The association between self-reported hypertension and depressive symptoms was explained partly by shared stress-related risk factors but not by life-style factors. Several stressors and life-style variables were risk factors for elevated blood pressure independently of depressive symptoms. The findings are consistent with studies that have measured hypertension variously by either self-report or blood pressure. Possible explanations were explored (labeling and help-seeking) but were not supported by the data. CONCLUSIONS: An association was found between self-reported hypertension and depressive symptoms, which was explained partly by shared stress-related risk factors. Elevated blood pressure was associated with stressors and life-style factors but not with depressive symptomatology. Research on illness representations and cultural dimensions of health suggest avenues for further investigation.

Adult↗

Evidence for somatic mutation and affinity maturation of diabetes associated human autoantibodies to glutamate decarboxylase.

The processes that lead to the production of islet cell autoantibodies in insulin-dependent (type 1) diabetes mellitus (IDDM) are largely unknown. Humoral autoimmunity may be the result of an antigen-independent polyclonal B cell activation, or a consequence of an antigen driven B cell activation and selection for the antigen. We have analysed the gene elements encoding the immunoglobulin variable regions of seven human monoclonal islet cell antibodies (MICA) 1-7 directed to the major islet autoantigen glutamate decarboxylase (GAD65). These autoantibodies were derived from two patients with newly diagnosed IDDM. The variable gene regions of the MICA revealed different sequences, and no relation between V gene usage and shared epitope recognition of the MICA was evident. An elevated usage of VH 1, VH 4 and Vlambda 2 gene segments was observed. The underrepresentation of VH 3 family members in the MICA discriminated them from most autoantibodies. The high relative avidities for GAD65 of MICA 1, 3, 4 and 6 and their high, nonrandom ratio of replacement versus silent mutations in the antigen binding regions indicated that the humoral response to GAD65 is driven by the antigen. MICA 2, 5 and 7 showed as well an excess of replacement mutations in the antigen binding regions, but revealed lower relative avidities for their antigen. Since these clones accumulated many somatic mutations in their variable gene regions, they may be characteristic for later stages of the autoimmune disease. The results suggest that, in humans, an antigen driven B cell activation and affinity maturation process may contribute to the production of GAD65-autoantibodies found in patients with IDDM.

Antibodies, Monoclonal↗

Child psychopathy: theories, measurement, and relations with the development and persistence of conduct problems.

To develop more accurate explanatory and predictive models of child and adolescent conduct problems, interest has grown in examining psychopathic traits in youth. The presence or absence of these traits may help to identify unique etiological pathways in the development of antisocial behavior. The current review provides a detailed summary and analysis of (a) the conceptualization and measurement of child and adolescent psychopathy, (b) research on relations between psychopathic traits and a range of conduct problems and associated variables, (c) efforts to utilize data on child and adolescent psychopathy to delineate a subgroup of youth whose conduct problems share a relatively homogenous etiology and developmental trajectory, and (d) current challenges and limitations in the study of youth psychopathy and directions for future research efforts. Specific sections include the origins of the youth psychopathy construct, conceptualization and measurement, relations between psychopathic traits and conduct problems, relations between measures of psychopathy and measures of individual and contextual variables, efforts to identify a unique subgroup of children with conduct problems using psychopathic traits, and finally, challenges that face the field and goals for the next generation of research.

Antisocial Personality Disorder↗

Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity.

OBJECTIVE: A prospective clinical study of patients with recent onset rheumatoid arthritis (RA) to examine the relationship between inflammatory disease activity and joint destruction in a 4 year followup, and to evaluate prognostic markers for severe joint erosions early in the disease. METHODS: Eighty-seven patients with RA according to the American College of Rheumatology criteria and a disease duration < 2 years were followed for an observation time of 2 to 4 years (mean 3.1 yrs). Variables of clinical and laboratory disease activity were monitored, and HLA-DRB1 alleles were determined. Hand and foot radiographs were taken every 6 months. RESULTS: Multivariate analysis of independent contributions of covariates to progression of joint destruction resulted in a mixed effect regression model with significant influences for the presence of a shared epitope (SE) positive DR4 allele (SE+ DR4+; p = 0.007), rheumatoid factor (RF) IgA (p = 0.01), and sex (p = 0.059), but not for clinical variables or acute phase reactants. The odds ratio to reach a Larsen score above 32 during the observation period of 4 years was increased in patients positive for RF IgM (OR 2.7, p = 0.019), for the shared epitope on a DR4 allele (OR 8.6, p < 0.005), and in patients with erosions already at study entry (OR 11.9, p = 0.001). The highest sensitivity and specificity for the prediction of severe bone destruction (84% and 79%) were found when the presence of either a SE+ DR4 allele or of early erosions was used as a prognostic marker (OR 20.4, p < 0.0001). CONCLUSION: Our results show the pace of joint destruction in RA to be influenced by the presence of SE+ DR4 alleles, RF production, and sex and by the presence of erosive disease at presentation. Those prognostic markers exert their influence independently from the inflammatory disease activity.

Adult↗

Variable region sequence of the light chain from a Waldenströms IgM with specificity for phosphorylcholine.

The variable region sequence of the light chain from the human IgM FR with binding activity for phosphorylcholine has been determined. Automated Edman degradation was used for the whole chain and for a large cyanogen bromide fragment comprising the third hypervariable region and the entire constant part. The rest of the sequence was established by means of the "Dansyl-Edman" technique with tryptic peptides. The sequence of light chain FR can be assigned to the subgroup II of human light chains with which it shares 92% homology within the nonhypervariable (frame-work) residues. There is no apparent sequence homology betweeen the variable region of the human light chain FR and the aminoterminal 41 residues of the light chains published so far from the mouse myeloma proteins TEPC 15, HOPC 8, S 107, and McPC 603 with phosphorylcholine binding activity. Recent data on the light chain of the phosphorylcholin binding mouse myeloma protein MOPC 167 (see Conclusion), however, indicate a considerable structural homology between the first hypervariable region of this murine protein and that of the human IgM FR, suggesting that both IgM FR and IgA MOPC 167 might have been selected by similar antigens.

Amino Acid Sequence↗

Statistical methods in epidemiology. VI. Correlation and regression: the same or different?

PURPOSE: The statistical terms 'correlation' and 'regression' are frequently mistaken for each other in the scientific literature. Why this is so is unclear. This paper discusses their differences/ similarities arguing that in most circumstances regression is the most appropriate technique to use, since regression incorporates a notion of dependency of one variable on another. METHOD: Pearson's correlation coefficient (r) is introduced as a method for estimating the degree of linear association between two normally distributed variables. The problem of least squares' regression (when y depends on x) is introduced by considering the best-fitting straight line between points on a scatter plot. RESULTS: Correlation, regression analysis and residual estimation are discussed by taking examples from the author's own teaching experiences. CONCLUSIONS: Correlation and regression share some similarities. However, regression is the better technique to use because with it comes a notion of dependency of one variable upon another. Regression model checking includes residual examination. The importance of plotting and examination of residuals cannot be overemphasized. Residual examination should become as much a part of a regression analysis as the estimation of the regression coefficients themselves.

Epidemiologic Methods↗

Postural invariance in three-dimensional reaching and grasping movements.

The question of whether the final arm posture to be reached is determined in advance during prehension movements remains widely debated. To address this issue, we designed a psychophysical experiment in which human subjects were instructed to reach and grasp, with their right arm, a small sphere presented at various locations. In some trials the sphere remained stationary, while in others (the perturbed trials) it suddenly jumped, at movement onset, to a new unpredictable position. Our data indicate that the final configuration of the upper limb is highly predictable for a given location of the sphere. For movements directed at stationary objects, the variability of the final arm posture was very small in relation to the variability allowed by joint redundancy. For movements directed at "jumping" objects, the initial motor response was quickly amended, allowing an accurate grasp. The final arm posture reached at the end of the perturbed trials was neither different from nor more variable than the final arm posture reached at the end of the corresponding stationary trials (i.e. the trials sharing the same final object location). This latter result is not trivial, considering both joint redundancy and the motor reorganization imposed by the change in sphere location. In contrast to earlier observations, our data cannot be accounted for by biomechanical or functional factors. Indeed, the spherical object used in the present study did not constrain the final arm configuration or the hand trajectory. When considered together, our data support the idea that the final posture to be reached is planned in advance and used as a control variable by the central nervous system.

Adult↗

Evaluating and understanding performance testing in COPD patients.

PURPOSE: There is increasing interest in the use of performance tests to assess physical function among patients with debilitating diseases. The purpose of this study was to describe the measurement properties of a performance test battery used in the Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial and to explore how well-selected physiologic and psychosocial measures explained test performance. METHODS: To assess test-retest reliability of the performance tests, older patients with chronic obstructive pulmonary disease (n = 30) completed, on two different occasions, a 6-minute walk for distance, a timed stair climb, and a timed elevated-arm task. In addition, stepwise regression analyses were conducted on a larger sample (n = 209) to examine how effective conceptually relevant physiologic and psychosocial variables were at explaining variation in task performance. RESULTS: Results showed that all three performance tasks had good test-retest reliability (all coefficients > 0.80) and shared variance in expected directions with VO2peak, forced expiratory volume in 1 second (FEV1), and self-reported disability. Regression analyses suggest that VO2peak, FEV1, self-efficacy, and self-reported disability are important variables to consider in attempts to understand performance-related disability in patients with chronic obstructive pulmonary disease (COPD). CONCLUSIONS: The physical performance test battery appears to be a reliable means of assessing physical functioning in older patients with COPD. Furthermore, findings support the important role that VO2peak plays in task performance and suggest that patients' perceptions should be given careful consideration when attempting to understand physical decline in clinical settings.

Aged↗

Evidence that the variable regions of the central domain of VlsE are antigenic during infection with lyme disease spirochetes.

It has been postulated that the vls system of the Lyme disease spirochetes contributes to immune evasion through antigenic variation. While it is clear that vlsE undergoes sequence change within its variable regions at a high frequency during the early stages of infection, a definitive role in immune evasion has not been demonstrated. In this report we assessed the murine and human humoral immune response to recombinant (r)-VlsE variants that originally arose during infection in mice. Immunoblot analyses of r-VlsE variants were conducted by using serum samples collected from mice infected with Borrelia burgdorferi clones that carried different vlsE variants. All of the r-VlsE variants were recognized by infection sera regardless of the identity of the infecting clone or isolate. In addition, all variants were immunoreactive with a panel of human Lyme disease patient serum samples. It is evident from these analyses that the infection-induced VlsE variants share common epitopes that reside within conserved segments of these proteins. However, preabsorption experiments revealed that the variable regions of the central domain of VlsE, which undergo rapid mutation during infection, also influence the antigenic properties of the protein. A subset of the antibodies elicited against vlsE variants that differ in the sequences of their variable regions were found to be variant specific. Hence, in spite of a robust antibody response to conserved segments of VlsE, infection-induced sequence changes within the variable regions alter the antigenicity of VlsE. These results provide the first direct evidence of antigenic variation in the VlsE protein.

Animals↗

Patterns of genetic variation in rare and widespread plant congeners.

Rare species are typically considered to maintain low levels of genetic variation, and this view has been supported by several reviews of large numbers of isozyme studies. Although these reviews have provided valuable data on levels of variability in plant species in general, and rare species in particular, these broad overviews involve comparisons that may confound the effects of rarity with a multitude of other factors that affect genetic variability. Additionally, the statistical analyses employed assume the data to be independent, which is not the case for organisms that share a common phylogenetic history. As the role of evolutionary history and historical constraints has become better understood, more researchers have studied widespread congeners when investigating the genetic diversity of rare species in an effort to control for these effects. We summarize the available data from such studies, comparing for rare and widespread congeners (1) the levels of genetic variability at the population and species levels and (2) measures of population substructuring. At the population level, we summarized data for percentage polymorphic loci (%P(pop)), mean number of alleles per locus (A(pop)), and observed heterozygosity (H(o)). Species-level measures used were percentage polymorphic loci (%P(spp)), mean number of alleles per locus (A(spp)), and total genetic diversity (H(T)). Indices of population subdivision (either F(ST) or G(ST)) were also examined. Using Wilcoxon signed rank tests, we found significant, but small, differences between rare and widespread species for all diversity measures except H(T). However, there does not appear to be a difference between rare and widespread congeners in terms of how genetic variation is partitioned within and among populations. Levels of diversity, for all measures examined, between rare and widespread congeners are highly correlated.

Journal Article↗