Prediction models for short children born small for gestational age (SGA) covering the total growth phase. Analyses based on data from KIGS (Pfizer International Growth Database)

<p>Abstract</p> <p>Background</p> <p>Mathematical models can be developed to predict growth in short children treated with growth hormone (GH). These models can serve to optimize and individualize treatment in terms of height outcomes and costs. The aims of this study were to compile existing prediction models for short children born SGA (SGA), to develop new models and to validate the algorithms.</p> <p>Methods</p> <p>Existing models to predict height velocity (HV) for the first two and the fourth prepubertal years and during total pubertal growth (TPG) on GH were applied to SGA children from the KIGS (Pfizer International Growth Database) - 1^styear: N = 2340; 2^ndyear: N = 1358; 4^thyear: N = 182; TPG: N = 59. A new prediction model was developed for the 3^rdprepubertal year based upon 317 children by means of the all-possible regression approach, using Mallow's C(p) criterion.</p> <p>Results</p> <p>The comparison between the observed and predicted height velocity showed no significant difference when the existing prediction models were applied to new cohorts. A model for predicting HV during the 3^rdyear explained 33% of the variability with an error SD of 1.0 cm/year. The predictors were (in order of importance): HV previous year; chronological age; weight SDS; mid-parent height SDS and GH dose.</p> <p>Conclusions</p> <p>Models to predict growth to GH from prepubertal years to adult height are available for short children born SGA. The models utilize easily accessible predictors and are accurate. The overall explained variability in SGA is relatively low, due to the heterogeneity of the disorder. The models can be used to provide patients with a realistic expectation of treatment, and may help to identify compliance problems or other underlying causes of treatment failure.</p

Are Cuckoos Maximizing Egg Mimicry by Selecting Host Individuals with Better Matching Egg Phenotypes?

Background: Avian brood parasites and their hosts are involved in complex offence-defense coevolutionary arms races. The most common pair of reciprocal adaptations in these systems is egg discrimination by hosts and egg mimicry by parasites. As mimicry improves, more advanced host adaptations evolve such as decreased intra- and increased interclutch variation in egg appearance to facilitate detection of parasitic eggs. As interclutch variation increases, parasites able to choose hosts matching best their own egg phenotype should be selected, but this requires that parasites know their own egg phenotype and select host nests correspondingly. Methodology/Principal Findings: We compared egg mimicry of common cuckoo Cuculus canorus eggs in naturally parasitized marsh warbler Acrocephalus palustris nests and their nearest unparasitized conspecific neighbors having similar laying dates and nest-site characteristics. Modeling of avian vision and image analyses revealed no evidence that cuckoos parasitize nests where their eggs better match the host eggs. Cuckoo eggs were as good mimics, in terms of background and spot color, background luminance, spotting pattern and egg size, of host eggs in the nests actually exploited as those in the neighboring unparasitized nests. Conclusions/Significance: We reviewed the evidence for brood parasites selecting better-matching host egg phenotypes from several relevant studies and argue that such selection probably cannot exist in host-parasite systems where hos

IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity