Introduction

The 31st Stoneburner Lecture Series was planned to present an overview of some important aspects of clinical nephrology that we hope are of interest to a wide audience. The faculty for this symposium was drawn largely from the Medical College of Virginia Nephrology Division, and we were fortunate to have Dr. George E. Schreiner, Professor of Medicine at Georgetown University and a long-time friend, as our Stoneburner Lecturer

Cancer and the Kidney

Cancer of the kidney is associated with a bewildering array of extrarenal symptoms, and conversely, tumors far removed from the kidney produce intriguing renal functional abnormalities. A variety of extrarenal complications are seen with hypernephromas, most of which rarely accompany Wilms tumors which grow rapidly and generally occur before the age of 7. Wilms tumors are quite susceptible to radiation therapy and surgery, and are to be strongly suspected when hypertension and an abdominal mass are found in a small child. Unless treated, they rapidly cause death and usually leave little opportunity for the patient to develop the striking extrarenal manifestations seen with hypernephroma

Evaluation of a metal fuselage frame selectively reinforced with filamentary composites for space shuttle application

The development of metal structures reinforced with filamentary composites as a weight saving feature of the space shuttle components is discussed. A frame was selected for study that was representative of the type of construction used in the bulk frames of the orbiter vehicle. Theoretical and experimental investigations were conducted. Component tests were performed to evaluate the critical details used in the designs and to provide credibility to the weight saving results. A model frame was constructed of the reinforced metal material to provide a final evaluation of the construction under realistic load conditions

Carbon accretion in unthinned and thinned young-growth forest stands of the Alaskan perhumid coastal temperate rainforest.

BACKGROUND: Accounting for carbon gains and losses in young-growth forests is a key part of carbon assessments. A common silvicultural practice in young forests is thinning to increase the growth rate of residual trees. However, the effect of thinning on total stand carbon stock in these stands is uncertain. In this study we used data from 284 long-term growth and yield plots to quantify the carbon stock in unthinned and thinned young growth conifer stands in the Alaskan coastal temperate rainforest. We estimated carbon stocks and carbon accretion rates for three thinning treatments (basal area removal of 47, 60, and 73 %) and a no-thin treatment across a range of productivity classes and ages. We also accounted for the carbon content in dead trees to quantify the influence of both thinning and natural mortality in unthinned stands. RESULTS: The total tree carbon stock in naturally-regenerating unthinned young-growth forests estimated as the asymptote of the accretion curve was 484 (±26) Mg C ha-1 for live and dead trees and 398 (±20) Mg C ha-1 for live trees only. The total tree carbon stock was reduced by 16, 26, and 39 % at stand age 40 y across the increasing range of basal area removal. Modeled linear carbon accretion rates of stands 40 years after treatment were not markedly different with increasing intensity of basal area removal from reference stand values of 4.45 Mg C ha-1 year-1to treatment stand values of 5.01, 4.83, and 4.68 Mg C ha-1 year-1 respectively. However, the carbon stock reduction in thinned stands compared to the stock of carbon in the unthinned plots was maintained over the entire 100 year period of observation. CONCLUSIONS: Thinning treatments in regenerating forest stands reduce forest carbon stocks, while carbon accretion rates recovered and were similar to unthinned stands. However, that the reduction of carbon stocks in thinned stands persisted for a century indicate that the unthinned treatment option is the optimal choice for short-term carbon sequestration. Other ecologically beneficial results of thinning may override the loss of carbon due to treatment. Our model estimates can be used to calculate regional carbon losses, alleviating uncertainty in calculating the carbon cost of the treatments

Effects of intra-animal nephron heterogeneity on studies of glomerular dynamics

Effects of intra-animal nephron heterogeneity on studies of glomerular dynamics. Quintuplicate determinations of the parameters measured in studies of glomerular dynamics revealed that the intra-animal coefficients of variation for Bowman's space and star vessel pressures, nephron filtration rate, and filtration fractions were 54 to 72% larger than the corresponding interanimal coefficients of variation; those for glomerular capillary pressure were more nearly equal. With a net efferent filtration pressure (ΔPE) of 10.6 ± SEM 1.92mm Hg, the rats were far from filtration pressure equilibrium and the calculated ultrafiltration coefficient (Kf) of 2.1 ± SEM 0.2 nl/min ·2mm Hg was lower than in many other studies. Statistical analysis revealed that the precision of estimates of both the measured and the derived parameters in glomerular dynamic studies is affected appreciably by ignoring the intra-animal effect. The importance of the intra-animal variance in glomerular dynamic studies is greatest when only one or two samples of each measured parameter are obtained in every rat (k = 1 or 2) and least when k is large. Triplicate sampling provides combined SEMS that are not greatly larger than those obtained with k = 5, however, and offers the greatest economy in studies of glomerular dynamics. The number of animals required to provide values with ΔPE and Kf that are within ± 20% of the “true” values is rather large.Effets de l'hétérogénéité néphronique intra-animale sur les études de la dynamique glomérulaire. Des déterminations en quintuple des paramètres mesurés dans les études de la dynamique glomérulaire ont révélé que les coefficients de variation intra-animale pour les pressions dans l'espace de Bowman et les vaisseaux étoilés, le débit de filtration glomérulaire et les fractions de filtration étaient 54 à 74% plus grandes que les coefficients de variation inter-animale correspondants; ceux de la pression capillaire glomérulaire étaient plus proches. Avec une pression de filtration effèrente nette (ΔPE) de 10,6 ± SEM 1,92mm Hg, les rats étaient loin d'une pression de filtration en équilibre, et le coefficient d'ultrafiltration calculé (Kf) de 2,1 ± SEM 0,2 nl/min ·2mm Hg était plus faible que lors de nombreuses autres études. L'analyse statistique a révélé que la précision des paramètres mesurés et déduits des études de la dynamique glomérulaire est affectée de façon appréciable en ignorant l'effet intra-animal. L'importance de la variance intra-animale dans les études de la dynamique glomérulaire est très grande lorsque seulement un ou deux échantillons de chaque paramètre mesuré sont obtenus chez chaque rat (k = 1 ou 2), et moindre lorsque k est élevé. Un échantillon-age triple offre cependant des SEM combinés qui ne sont pas beaucoup plus grands que ceux obtenus pour k = 5, cependant, et offre la plus forte économie lors des mesures de la dynamique glomérulaire. Le nombre d'animaux nécessaires pour obtenir des valeurs avec ΔE et Kf entre ± 20% des valeurs “vraies” est assez grand

Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination

Street-view greenspace exposure and objective sleep characteristics among children

Greenspace may benefit sleep by enhancing physical activity, reducing stress or air pollution exposure. Studies on greenspace and children's sleep are limited, and most use satellite-derived measures that do not capture ground-level exposures that may be important for sleep. We examined associations of street view imagery (SVI)-based greenspace with sleep in Project Viva, a Massachusetts pre-birth cohort. We used deep learning algorithms to derive novel metrics of greenspace (e.g., %trees, %grass) from SVI within 250m of participant residential addresses during 2007–2010 (mid-childhood, mean age 7.9 years) and 2012–2016 (early adolescence, 13.2y) (N = 533). In early adolescence, participants completed >5 days of wrist actigraphy. Sleep duration, efficiency, and time awake after sleep onset (WASO) were derived from actigraph data. We used linear regression to examine cross-sectional and prospective associations of mid-childhood and early adolescence greenspace exposure with early adolescence sleep, adjusting for confounders. We compared associations with satellite-based greenspace (Normalized Difference Vegetation Index, NDVI). In unadjusted models, mid-childhood SVI-based total greenspace and %trees (per interquartile range) were associated with longer sleep duration at early adolescence (9.4 min/day; 95%CI:3.2,15.7; 8.1; 95%CI:1.7,14.6 respectively). However, in fully adjusted models, only the association between %grass at mid-childhood and WASO was observed (4.1; 95%CI:0.2,7.9). No associations were observed between greenspace and sleep efficiency, nor in cross-sectional early adolescence models. The association between greenspace and sleep differed by racial and socioeconomic subgroups. For example, among Black participants, higher NDVI was associated with better sleep, in neighborhoods with low socio-economic status (SES), higher %grass was associated with worse sleep, and in neighborhoods with high SES, higher total greenspace and %grass were associated with better sleep time. SVI metrics may have the potential to identify specific features of greenspace that affect sleep

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices

Background: Diverse perspectives have influenced fish consumption choices

Correlations among adiposity measures in school-aged children

BACKGROUND: Given that it is not feasible to use dual x-ray absorptiometry (DXA) or other reference methods to measure adiposity in all pediatric clinical and research settings, it is important to identify reasonable alternatives. Therefore, we sought to determine the extent to which other adiposity measures were correlated with DXA fat mass in school-aged children. METHODS: In 1110 children aged 6.5-10.9 years in the pre-birth cohort Project Viva, we calculated Spearman correlation coefficients between DXA (n=875) and other adiposity measures including body mass index (BMI), skinfold thickness, circumferences, and bioimpedance. We also computed correlations between lean body mass measures. RESULTS: 50.0% of the children were female and 36.5% were non-white. Mean (SD) BMI was 17.2 (3.1) and total fat mass by DXA was 7.5 (3.9) kg. DXA total fat mass was highly correlated with BMI (r(s)=0.83), bioimpedance total fat (r(s)=0.87), and sum of skinfolds (r(s)=0.90), and DXA trunk fat was highly correlated with waist circumference (r(s)=0.79). Correlations of BMI with other adiposity indices were high, e.g., with waist circumference (r(s)=0.86) and sum of subscapular plus triceps skinfolds (r(s)=0.79). DXA fat-free mass and bioimpedance fat-free mass were highly correlated (r(s)=0.94). CONCLUSIONS: In school-aged children, BMI, sum of skinfolds, and other adiposity measures were strongly correlated with DXA fat mass. Although these measurement methods have limitations, BMI and skinfolds are adequate surrogate measures of relative adiposity in children when DXA is not practical