Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

Increasing Perceptions of Self-Worth in Preadolescents Diagnosed with ADHD

Purpose: To test the effectiveness of a school-based, nurse-facilitated support group in increasing perceptions of scholastic competence, social acceptance, behavioral conduct, perceived athletic competence, perceived physical appearance, and perceived global self-worth in preadolescents diagnosed with attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD).
Design: A quasi-experimental design with 65 preadolescents diagnosed with ADD or ADHD in an upper-middle class community in the United States.
Methods: Participants randomly assigned to either the control or experimental group completed Harter's Self-Perception Profile for Children instrument at the beginning of the study and 4 weeks later. Students in the experimental condition participated in a school-nurse facilitated support group which met twice weekly for 4 weeks.
Findings: Participants in the support group had increased scores on each of the six subscales, with significant increases on four of the subscales, including perceived social acceptance, perceived athletic competence, perceived physical appearance, and perceived global self-worth.
Conclusion: Participation in a school-based, nurse-led support group was positively associated with perception of self-worth in preadolescents diagnosed with ADD or ADHD.     

Optimal control of a revenue management system with dynamic pricing facing linear demand

This paper considers a dynamic pricing problem over a finite horizon where demand for a product is a time‐varying linear function of price. It is assumed that at the start of the horizon there is a fixed amount of the product available. The decision problem is to determine the optimal price at each time period in order to maximize the total revenue generated from the sale of the product. In order to obtain structural results we formulate the decision problem as an optimal control problem and solve it using Pontryagin's principle. For those problems which are not easily solvable when formulated as an optimal control problem, we present a simple convergent algorithm based on Pontryagin's principle that involves solving a sequence of very small quadratic programming (QP) problems. We also consider the case where the initial inventory of the product is a decision variable. We then analyse the two‐product version of the problem where the linear demand functions are defined in the sense of Bertrand and we again solve the problem using Pontryagin's principle. A special case of the optimal control problem is solved by transforming it into a linear complementarity problem. For the two‐product problem we again present a simple algorithm that involves solving a sequence of small QP problems and also consider the case where the initial inventory levels are decision variables. Copyright © 2006 John Wiley & Sons, Ltd.     

High Prevalence of Developmental Disabilities in Children Admitted to a General Pediatric Inpatient Unit

Objective: Evaluate a) the prevalence of developmental disabilities (DD) in children admitted to a general pediatrics inpatient unit, and b) the number of children admitted to the unit with previously undiagnosed developmental disability. Methods: Prevalence was evaluated through retrospective record review. Subjects: One hundred ninety children older than five months of age admitted to a general pediatric unit. Results: Of 190 children admitted, 155 (81.6%) had adequate developmental screening documented in the record. Forty-nine (25.7% of total, 31.6% of screened) had a developmental disability, 22 (12.1% of total, 14.8% of screened) had a previously unrecognized disability. Sample prevalence of DD was: cerebral palsy (6.8%), developmental delay or mental retardation (8.4%), language delay (4.6%), learning disability (8.2%), and hearing loss (1.5%). New diagnoses included: three children with probable mental retardation (MR), nine with learning disability (may include mild MR), seven with language delay, three with abnormal motor skills (fine and/or gross motor), one each of: neurofibromatosis type I, hearing loss, cerebral palsy, dysphagia. Some children had more than one new diagnosis. Conclusion: The prevalence of disabilities in a general pediatrics inpatient unit is much higher than the prevalence in the community. Because almost half of the disabilities were previously unrecognized, acute hospitalization is an excellent opportunity to conduct developmental screening.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

ITERATIVE DYNAMIC PROGRAMMING FOR MINIMUM ENERGY CONTROL PROBLEMS WITH TIME DELAY

This paper presents the use of iterative dynamic programming employing exact penalty functions for minimum energy control problems. We show that exact continuously non-differentiable penalty functions are superior to continuously differentiable penalty functions in terms of satisfying final state constraints. We also demonstrate that the choice of an appropriate penalty function factor depends on the relative size of the time delay with respect to the final time and on the expected value of the energy consumption. A quadratic approximation (QA) of the delayed variables is much better than a linear approximation (LA) of the same for relatively large time delays. The QA improves the rate of convergence and avoids the formation of ‘kinks‘. A more general way of selecting appropriate penalty function factors is given and the results obtained using four illustrative examples of varying complexity corroborate the efficacy of the method.     

Pleiotropy in Coffin-Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc.