RESUMEN
Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada. Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0-5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators. Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46-5.64), otitis media (aOR:1.83, 95%CI:1.05-3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09-2.77), compared to non-carriers. Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps.
RESUMEN
The incidence of Severe Combined Immunodeficiency (SCID) in Manitoba, (1/15,000), is at least three to four times higher than the national average and that reported from other jurisdictions. It is overrepresented in two population groups: Mennonites (ZAP70 founder mutation) and First Nations of Northern Cree ancestry (IKBKB founder mutation). We have previously demonstrated that in these two populations the most widely utilized T-cell receptor excision circle (TREC) assay is an ineffective newborn screening test to detect SCID as these patients have normal numbers of mature T-cells. We have developed a semi-automated, closed tube, high resolution DNA melting procedure to simultaneously genotype both of these mutations from the same newborn blood spot DNA extract used for the TREC assay. Parallel analysis of all newborn screening specimens utilizing both TREC analysis and the high-resolution DNA procedure should provide as complete ascertainment as possible of SCID in the Manitoba population.
RESUMEN
Recent evidence that young children seem to both understand false belief in one sense, but not in another, has led to two-systems theorizing about mindreading. By analyzing the most detailed two-systems approach in studying social cognition-the theory of mindreading defended by Ian Apperly and Stephen Butterfill-I argue that that even when dutifully constructed, two-systems approaches in social cognition struggle to adequately define the mindreading systems in terms of signature processing limits, an issue that becomes most apparent when investigating mindreading in infancy. I end the article by developing several challenges that face any two-systems account of mindreading.