Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Rapid whole genome sequencing and precision neonatology

Traditionally, genetic testing has been too slow or perceived to be impractical to initial management of the critically ill neonate. Technological advances have led to the ability to sequence and interpret the entire genome of a neonate in less than 50 hours. As the cost and speed of testing decreases, the utility of whole genome sequencing (WGS) of neonates for acute and latent genetic illness increases. Analyzing the entire genome allows for concomitant evaluation of the currently identified 5,430 single gene diseases. When applied to a select population of ill infants in a level IV neonatal intensive care unit, WGS yielded a diagnosis of a causative genetic disease in 57% of patients. These diagnoses may lead to clinical management changes ranging from transition to palliative care for uniformly lethal conditions to alteration or initiation of medical or surgical therapy to improve outcomes in others. Thus, institution of 2-day WGS at time of acute presentation opens the possibility of early implementation of precision medicine. This implementation may create opportunities for early interventional therapies, which would frequently be novel or off-label, that may alter disease trajectory in infants with what would otherwise be fatal disease. Widespread deployment of rapid WGS and precision medicine will raise ethical issues pertaining to interpretation of variants of unknown significance, discovery of incidental findings related to adult onset conditions and carrier status, and implementation of medical therapies for which little is known in terms of risks and benefits. Despite these challenges, precision neonatology has significant potential both to decrease infant mortality related to genetic diseases with onset in newborns and to facilitate parental decision-making regarding transition to palliative care

Cost Overrun at the Norwegian Continental Shelf: The Element of Surprise

We examine drivers of cost overruns in Norwegian development projects in the oil and gas sector. The multivariate longitudinal econometric analysis employs a unique and detailed dataset consisting of 80 different projects between 2000 and 2015. Among the significant results, we find that the unexpected change in economic activity has a positive effect on the overruns; there is a considerable positive momentum in the transitional cost overruns; more experienced operators tend to incur less overruns; finally, that the size of the investment of the projects has a positive impact on the overruns. Further, we find evidence that the current economic activity matters to an extent, but it is the unexpected change in activity that is the pivotal factor

Relationship between protein-energy malnutrition, vitamin A, and parasitoses in children living in Brasília Relação entre desnutrição energético-protéica, vitamina A, e parasitoses em crianças vivendo em Brasília

It is still controversial whether intestinal parasitic infections can influence the nutritional status of children. The relationship between protein-energy malnutrition, vitamin A and parasitic infections was evaluated in 124 children. The food intake estimated by recall method was generally low and poor. Seventy five percent of the children were infected with intestinal parasites. The mean±SD weight-for-age and height-for-age Z-score were skewed one standard deviation to the left, when compared to normal standards. An association was found between protein-energy malnutrition and Giardia lamblia, but not with Ascaris lumbricoides or Hymenolepis nana infection. Only Giardia-infected children had a decreased weight-for-age and weight-for-height Z-score. Hypovitaminosis A was a major nutritional problem, but no relationship between this deficiency and parasitic infection was found. Our data indicate that low and poor food intake were the major cause of protein-energy malnutrition among the children, and except for Giardia, this was not influenced by parasitic infections.<br>É controverso se parasitismo intestinal interfere no estado nutricional. A relação entre desnutrição energético-protéica, vitamina A e parasitoses intestinais foi avaliada em 124 crianças. A ingestão alimentar estimada pelo método recordatório mostrou-se deficiente em quantidade e qualidade. Setenta e cinco porcento das crianças estavam parasitadas. A média±DP do Z-escore do peso-para-idade e altura-para-idade da população estudada desviou-se aproximadamente um DP para a esquerda em relação aos padrões normais. Encontrou-se associação entre desnutrição energético-protéica e parasitismo por Giardia lamblia, mas não por Ascaris lumbricoides ou Hymenolepis nana. Somente crianças infectadas por Giardia mostraram deficiência do peso-para-idade e peso-para-altura avaliado pelo Z-escore. Hipovitaminose A foi um importante problema nutricional, mas não houve relação entre esta deficiência e parasitoses intestinais. Nossos dados indicam que deficiência na quantidade e na qualidade da ingestão foram os principais problemas causando desnutrição-energético protéica, e exceto para Giardia, não foi influenciado pelo parasitismo por helmintos intestinais