Investing in early human development: Timing and economic efficiency

Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.     

Immune risk phenotype is associated with nosocomial lung infections in elderly in-patients

Background

Nosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters.

Results

We included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180; p = 0.036).

Conclusion

Immunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term.     

Carbon debt and carbon sequestration parity in forest bioenergy production

The capacity for forests to aid in climate change mitigation efforts is substantial but will ultimately depend on their management. If forests remain unharvested, they can further mitigate the increases in atmospheric CO₂ that result from fossil fuel combustion and deforestation. Alternatively, they can be harvested for bioenergy production and serve as a substitute for fossil fuels, though such a practice could reduce terrestrial C storage and thereby increase atmospheric CO₂ concentrations in the near‐term. Here, we used an ecosystem simulation model to ascertain the effectiveness of using forest bioenergy as a substitute for fossil fuels, drawing from a broad range of land‐use histories, harvesting regimes, ecosystem characteristics, and bioenergy conversion efficiencies. Results demonstrate that the times required for bioenergy substitutions to repay the C Debt incurred from biomass harvest are usually much shorter (< 100 years) than the time required for bioenergy production to substitute the amount of C that would be stored if the forest were left unharvested entirely, a point we refer to as C Sequestration Parity. The effectiveness of substituting woody bioenergy for fossil fuels is highly dependent on the factors that determine bioenergy conversion efficiency, such as the C emissions released during the harvest, transport, and firing of woody biomass. Consideration of the frequency and intensity of biomass harvests should also be given; performing total harvests (clear‐cutting) at high‐frequency may produce more bioenergy than less intensive harvesting regimes but may decrease C storage and thereby prolong the time required to achieve C Sequestration Parity.     

Multiple forms of the glucocorticoid receptor steroid binding protein identified by affinity labeling and high-resolution two-dimensional electrophoresis

Potential charge heterogeneity within the glucocorticoid binding protein (GBP) of the glucocorticoid receptor was examined by a combination of affinity labeling, immunopurification, and high-resolution two-dimensional (2D) gel electrophoresis. One-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of [3H]dexamethasone 21-mesylate ([3H]DM) labeled cytosol identified a major, competable, component of Mr approximately equal to 92 000 (92K). This component was recognized by anti-human glucocorticoid receptor antibodies but not by nonimmune serum, indicating that the 92K component was the reduced denatured GBP. Examination of [3H]DM-labeled GBP by conventional 2D electrophoresis utilizing equilibrium isoelectric focusing in the first dimension failed to resolve the 92K GBP into discrete isoelectric components. This behavior was not representative of other, nonspecifically [3H]DM-labeled proteins or proteins in general. Nonequilibrium pH gradient electrophoresis (NEPHGE) was therefore employed to achieve separation in the first dimension. Immunopurified, [3H]DM-labeled GBP subjected to NEPHGE reached isoelectric equilibrium after 6 h of electrophoresis at 400 V. A single, broad peak of radioactivity was identified at pH approximately equal to 6.3. Second-dimension analysis of the NEPHGE-separated GBP by SDS-PAGE resolved this peak into two discrete, 92K, isoforms of apparent pI = 5.7 and 6.0-6.5. The GBP charge heterogeneity was confirmed by NEPHGE 2D analysis of [3H]DM-labeled GBP prepared directly from crude cytosol. Two isoforms indistinguishable from those observed in immunopurified samples were identified. An additional, more acidic, isoform (apparent pI approximately equal to 5.2) was also identified. Thus, there are at least two, and perhaps three, isoforms of the GBP. These data therefore suggest that there is significant charge heterogeneity in the GBP of the glucocorticoid receptor.     

Calcium, magnesium, and potassium in hair of deer from areas of contrasting soil productivity

Differences in mineral nutrient composition of soils have been considered to affect health and population characteristics of free-ranging animals, particularly herbivores. Contents of Ca, Mg, and K in hair of female fawn white-tailed deer (Odocoileus virginianus) were measured for eight consecutive years to determine if soil and annual effects occurred in two areas of contrasting soil productivity in Illinois. Soil differences may account for some of the autumnal weight difference (7.2 kg for 4 yrs of observation) observed in fawn does from the areas. Ca, Mg, and K were assayed, because these macronutrients were known to differ in soils of the areas and were presumed to differ in forages. In 6 of the 8 yrs, at least one element was significantly different (P ≤ 0.05) between areas. Significant (P ≤ 0.05) differences for K occurred in 5 yr, for Ca in 4 yr, and for Mg in 2 yr. Ca and Mg were lower in hair in 7 yr from deer collected from the area in which extractable Ca and Mg were higher in soils; that is, hair Ca and Mg levels tended to be inversely related to levels of plant-available Ca and Mg in soil. For 7 of the 8 yr, K content was lower in hair from the area of lower soil K content. Within one area, between-year differences occurred for Ca and K and for Ca and Mg in the other area. Between-year differences in diet selection and annual climatic effects on mineral uptake of forages, among other factors, may account for some of the latter differences. Results for hair analyses suggest that macronutrient differences in Ca, Mg, and K occur in the diets of these populations and may account for some of the weight difference observed between the areas.     

Interannual variability in dissolved inorganic nutrients in northern San Francisco Bay estuary

Nearly two decades of seasonal dissolved inorganic nutrient-salinity distributions in northern San Francisco Bay estuary (1960–1980) illustrate interannual variations in effects of river flow (a nutrient source) and phytoplankton productivity (a nutrient sink). During winter, nutrient sources dominate the nutrient-salinity distribution patterns (nutrients are at or exceed conservative mixing concentrations). During summer, however, the sources and sinks are in close competition. In summers of wet years, the effects of increased river flow often dominate the nutrient distributions (nutrients are at or less than conservative mixing concentrations), whereas in summers of dry years, phytoplankton productivity dominates (the very dry years 1976–1977 were an exception for reasons not yet clearly known). Such source/sink effects also vary with chemical species. During summer the control of phytoplankton on nutrient distributions is apparently strongest for ammonium, less so for nitrate and silica, and is the least for phosphate. Furthermore, the strength of the silica sink (diatom productivity) is at a maximum at intermediate river flows. This relation, which is in agreement with other studies based on phytoplankton abundance and enumeration, is significant to the extent that diatoms are an important food source for herbivores.The balance or lack of balance between nutrient sources and sinks varies from one estuary to another just as it can from one year to another within the same estuary. At one extreme, in some estuaries river flow dominates the estuarine dissolved inorganic nutrient distributions throughout most of the year. At the other extreme, phytoplankton productivity dominates. In northern San Francisco Bay, for example, the phytoplankton nutrient sink is not as strong as in less turbid estuaries. In this estuary, however, river effects, which produce or are associated with near-conservative nutrient distributions, are strong even at flows less than mean-annual flow. Thus, northern San Francisco Bay appears to be an estuary in between the two extremes and is shifted closer to one extreme or the other depending on interannual variations in river flow.     

Receptor-Mediated Phosphorylation of Astroglial Intermediate Filament Proteins in Cultured Astroglia

Primary cultures of purified astroglia have been shown to exhibit a variety of membrane receptors that regulate intracellular cyclic AMP levels. The experiments described in this paper were completed to examine the effect of such receptor agonists on protein phosphorylation in intact astroglia. An analysis of 32P-labelled proteins derived from whole cell extracts and separated via two-dimensional gel electrophoresis indicated that increasing cyclic AMP levels in astroglia stimulated the phosphorylation of two distinct proteins that had apparent molecular weights/isoelectric points (pI) of 51K/6.0 and 57K/5.7. Similar experiments with cultured meningeal cells indicated that only the 57K/5.7 protein was phosphorylated in response to elevated levels of cyclic AMP. The 51K/6.0 protein was never observed in gels derived from meningeal cells. Immunoblot experiments indicated that the 51K/6.0 protein stained with antiserum to glial fibrillary acidic protein (GFAP) and the 57K/5.7 protein stained with antibodies to vimentin. Concentration-effect studies indicate that these proteins are maximally phosphorylated at concentrations of receptor agonists that only slightly elevate cyclic AMP levels. All receptor agonists that have been shown to increase cyclic AMP levels appear similarly efficacious with respect to increasing the phosphorylation of the two proteins. These experiments suggest that the membrane receptors present on astroglia function, in part, to regulate phosphorylation of the intermediate filament proteins GFAP and vimentin.     

Water balance of conifer logs in early stages of decomposition

Seasonal and long-term changes in the water balance of conifer logs during the first 8 years of decomposition were studied in an old-growth Pseudotsuga/Tsuga forest in the Oregon Cascade Mountains. Measurements were made of the moisture content of outer bark, inner bark, sapwood, and heartwood and of the flow of water into and out of logs of four species (Abies amabilis, Pseudotsuga menziesii, Thuja plicata, and Tsuga heterophylla). After the logs had decomposed from 1 to 2 years, 38–47% of the canopy throughfall landing upon them ran off the surface, 29–34% leached from the bottom, and 21–30% was absorbed and evaporated. After 8 years of decomposition, water entering and then leaching from logs increased 1.3 times while runoff decreased a similar amount. The proportion of water stored by and evaporated from logs in this study indicates that in old growth forests they may intercept 2–5% of the canopy throughfall to the forest floor and that, even in early stages of decomposition, they may affect the hydrological cycle of Pacific Northwest old-growth forests.This is paper 2945 of the Forest Research Laboratory, Oregon State University, Corvallis