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Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.

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OBJECTIVES: To assess whether 21-deoxycortisol (21deoxy) can be used to predict 21-hydroxylase deficiency (21OHD) in newborns and to evaluate the influence of gestational age and the timing of collection on 21deoxy concentrations. STUDY DESIGN: 17-hydroxyprogesterone (17OHP) and 21deoxy levels were measured in 906 newborn screening specimens (851 unaffected newborns, 55 confirmed cases of 21OHD) to compare their ability to identify babies with 21OHD. In addition, these 2 steroids were assessed in the unaffected cohort to determine the influence of gestational age (ranging from 23 to 42 weeks) and the timing of specimen collection on the measured concentrations. RESULTS: The gestational age of the newborn impacted both 17OHP and 21deoxy concentrations, but the degree of influence was more substantial for 17OHP. Timing of collection did not affect 21deoxy concentration. Moreover, 21deoxy was a better predictor of 21OHD status compared with 17OHP, with little overlap in concentrations between the unaffected population and confirmed cases of 21OHD. A streamlined decision tree using solely 21deoxy (cutoff value, 0.85 ng/mL) yielded a 91.7% positive predictive value for 21OHD screening. CONCLUSIONS: Our findings demonstrate that 21deoxy is a key disease marker of 21OHD and can be used to improve the accuracy of newborn screening for this disorder.

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OBJECTIVE: To test the hypothesis that term-born small for gestational age (SGA) neonates have elevated thyroid-stimulating hormone (TSH) concentrations and an increased incidence of congenital hypothyroidism compared with non-SGA term neonates. STUDY DESIGN: This retrospective cohort study included all term neonates screened in Wisconsin in 2015 and 2016. The cohort was divided based on SGA status, defined as birth weight <10th percentile as calculated from the World Health Organization's sex-specific growth charts for age 0-2 years. TSH concentration on first newborn screening performed between birth and 96 hours of life and incidence of congenital hypothyroidism were compared between the SGA and non-SGA groups. RESULTS: A total of 115 466 term neonates, including 11 498 (9.96%) SGA neonates, were included in the study. TSH concentration and incidence of congenital hypothyroidism was significantly higher in the SGA group, but only TSH concentration remained significant when adjusted for potential confounding variables. CONCLUSIONS: Our data do not support a higher incidence of congenital hypothyroidism in term SGA neonates after adjusting for potential confounders. However, TSH concentrations were higher in term SGA neonates compared with term non-SGA neonates. The effects of mild thyroid hormone dysfunction on neurodevelopmental outcomes and development of chronic medical conditions merit long-term study.

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OBJECTIVES: To determine the incidence of congenital hypothyroidism in preterm infants and to identify associated risk factors. STUDY DESIGN: A population-based cohort study was performed in preterm infants born at <32 weeks of gestational age between 2012 and 2016 in Wisconsin. Newborn screening (NBS) results and demographic data were obtained from the Wisconsin State Laboratory of Hygiene. Congenital hypothyroidism was subdivided to early TSH elevation (eTSH) and delayed TSH elevation (dTSH). Multivariate logistic regression analyses were performed to identify demographic factors associated with dTSH. RESULTS: A total of 3137 preterm infants born at 22-31 weeks of gestational age were included in the study. Mean gestational age was 28.4 ± 2.4 weeks and mean birth weight was 1191 ± 399 g. Forty-nine infants were diagnosed with congenital hypothyroidism. The overall incidence of congenital hypothyroidism was 1.56%, including a 0.13% incidence of eTSH and a 1.43% incidence of dTSH. Birth weight <1000 g, multiple gestation, and initial TSH level were identified as independent predictors for dTSH. CONCLUSION: Targeted serial NBS in Wisconsin led to a higher rate of diagnosis of congenital hypothyroidism in preterm infants than has been reported previously. The majority (92%) of congenital hypothyroidism cases were diagnosed with dTSH. Birth weight <1000 g, multiple gestation, and elevated initial TSH level were associated with increased risk for development of dTSH. We recommend obtaining targeted serial NBS in preterm infants (<32 weeks of gestational age) to improve the detection of congenital hypothyroidism.

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This article presents a cultural adaptation of a group therapeutic approach that is being offered in the Bahamas. "The Family: People Helping People" project was designed as an intervention to improve socialization in New Providence, the Bahamian capital and its most heavily populated city. "The Family" group model offers support and training to improve communication in relationships and to encourage constructive emotional expression. This article will provide an overview of "The Family," address key elements of this approach that are culturally tailored, and offer clinical examples and note implications for group therapy training. This cultural adaptation offers helpful insights for addressing community problems, such as violence and societal fragmentation, and may inform the development of community-based group interventions in other settings.

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Thyroid dysfunction in adolescents treated with minocycline for acne has been previously described as transient effect and/or associated with autoimmune thyroiditis. We report nonimmune-mediated thyroid dysfunction associated with minocycline/doxycycline in 3 adolescents whose clinical courses suggest an adverse effect that may be more common, serious, and persistent than realized previously.

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OBJECTIVE: To develop a risk assessment model for early detection of hepatic steatosis using common anthropometric and metabolic markers. STUDY DESIGN: This was a cross-sectional study of 134 adolescent and young adult females, age 11-22 years (mean 13.3±2 years) from a middle school and clinics in Madison, Wisconsin. The ethnic distribution was 27% Hispanic and 73% non-Hispanic; the racial distribution was 64% Caucasian, 31% African-American, and 5% Asian, Fasting glucose, fasting insulin, alanine aminotransferase (ALT), body mass index (BMI), waist circumference (WC), and other metabolic markers were assessed. Hepatic fat was quantified using magnetic resonance imaging proton density fat fraction (MR-PDFF). Hepatic steatosis was defined as MR-PDFF>5.5%. Outcome measures were sensitivity, specificity, and positive predictive value (PPV) of BMI, WC, ALT, fasting insulin, and ethnicity as predictors of hepatic steatosis, individually and combined, in a risk assessment model. Classification and regression tree methodology was used to construct a decision tree for predicting hepatic steatosis. RESULTS: MR-PDFF revealed hepatic steatosis in 16% of subjects (27% overweight, 3% nonoverweight). Hispanic ethnicity conferred an OR of 4.26 (95% CI, 1.65-11.04; P=.003) for hepatic steatosis. BMI and ALT did not independently predict hepatic steatosis. A BMI>85% combined with ALT>65 U/L had 9% sensitivity, 100% specificity, and 100% PPV. Lowering the ALT value to 24 U/L increased the sensitivity to 68%, but reduced the PPV to 47%. A risk assessment model incorporating fasting insulin, total cholesterol, WC, and ethnicity increased sensitivity to 64%, specificity to 99% and PPV to 93%. CONCLUSION: A risk assessment model can increase specificity, sensitivity, and PPV for identifying the risk of hepatic steatosis and guide the efficient use of biopsy or imaging for early detection and intervention.

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OBJECTIVE: To develop a statewide school-based program of measuring and reporting cardiovascular fitness levels in children, and to create age- and sex-specific cardiovascular fitness percentile-based distribution curves. STUDY DESIGN: A pilot study validated cardiovascular fitness assessment with Progressive Aerobic Cardiovascular Endurance Run (PACER) testing as an accurate predictor of cardiovascular fitness measured by maximal oxygen consumption treadmill testing. Schools throughout the state were then recruited to perform PACER and body mass index (BMI) measurement and report de-identified data to a centralized database. RESULTS: Data on 20 631 individual students with a mean age 12.1 ± 2.0 years, BMI of 21.4 ± 5.1, and a cardiovascular fitness measured with PACER of 29.7 ± 18.2 laps (estimated maximal oxygen consumption of 36.5 mL/kg/min) were submitted for analysis. Standardized fitness percentiles were calculated for age and sex. CONCLUSIONS: This study demonstrates the feasibility of performing, reporting, and recording annual school-based assessments of cardiovascular fitness to develop standardized childhood fitness percentiles on the basis of age and sex. Such data can be useful in comparing populations and assessing initiatives that aim to improve childhood fitness. Because health consequences of obesity result from both adiposity and physical inactivity, supplementation of BMI measurement with tracking of cardiovascular fitness adds a valuable tool for large-scale health assessment.

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OBJECTIVE: To demonstrate the ability of a submaximal test to predict VO(2max) in overweight children. STUDY DESIGN: A total of 130 children, 11 to 14 years old, with body mass index >85 percentile for age and sex performed a submaximal walking test. VO(2max) was measured by using open circuit spirometry during a graded exercise test to volitional fatigue. An equation to predict VO(2max) was modeled by using the variables of sex, weight (kg), height (cm), heart rate (HR) after 4 minutes during the submaximal test (4minHR), HR difference (4minHR - resting HR), and submaximal treadmill speed (miles per hour [mph]) in 75% of the subjects. Validation was performed by using the remaining 25% of subjects. RESULTS: A total of 113 subjects achieved a maximal effort and was used in the statistical analysis. Development and validation groups were similar in all aspects. On validation, the mean square error was 241.06 with the predicted VO(2max) within 10% of the observed value in 67% of subjects. CONCLUSION: VO(2max) was accurately predicted in this cohort of overweight children by using a submaximal, treadmill-based testing protocol.

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OBJECTIVE: We studied the relationship between % body fat (%BF), cardiovascular fitness (CVF), and insulin resistance (IR) in overweight middle-school children. STUDY DESIGN: Middle school children (n = 106, body mass index [BMI] > 95th percentile for age) underwent evaluation of body composition, maximal volume of oxygen utilization (VO2) uptake/kg lean body mass (VO2max/kgLBM), and fasting glucose and insulin (FI) concentrations and derived homeostasis model assessment index (HOMA(IR)). RESULTS: Both %BF (r = .33, P < .001) and VO2max/kgLBM (r = -0.42, P < .0001) were significantly correlated with FI. Bivariate regression analysis revealed %BF (P = .008 vs FI, P = .035 vs HOMA(IR)) and VO2max/kgLBM (P < .001 vs FI, P = .009 vs HOMA(IR)) to be independent predictors of insulin sensitivity. In males, VO2max/kgLBM was a better predictor of FI and HOMA(IR) than %BF. CONCLUSIONS: In obese middle-school children, both %BF and VO2max/kgLBM are independent predictors of FI levels. The relationship between CVF and FI levels was significant in both sexes but was particularly profound and stronger than %BF in males. Efforts to reduce risk of type 2 diabetes mellitus in an increasingly obese child population should include exercise intervention sustained enough to improve CVF.

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We have generated immortal neuronal cell lines from normal and trisomy 16 (Ts16) mice, a model for Down syndrome (DS). Ts16 lines overexpress DS-related genes (App, amyloid precursor protein; Sod1, Cu/Zn superoxide dismutase) and show altered cholinergic function (reduced choline uptake, ChAT expression and fractional choline release after stimulation). As previous evidence has related amyloid to cholinergic dysfunction, we reduced APP expression using specific mRNA antisense sequences in our neuronal cell line named CTb, derived from Ts16 cerebral cortex, compared to a cell line derived from a normal animal, named CNh. After transfection, Western blot studies showed APP expression knockdown in CTb cells of 36% (24 hr), 40.4% (48 hr), and 50.2% (72 hr) compared to CNh. Under these reduced APP levels, we studied 3H-choline uptake in CTb and CNh cells. CTb, as reported previously, expressed reduced choline uptake compared to CNh cells (75%, 90%, and 69% reduction at 1, 2, and 5 min incubation, respectively). At 72 hr of APP knockdown, choline uptake levels were essentially similar in both cell types. Further, fractional release of 3H-choline in response to glutamate, nicotine, and depolarization with KCl showed a progressive increase after APP knockdown, reaching values similar to those of CNh after 72 hr of transfection. The results suggest that APP overexpression in CTb cells contributes to impaired cholinergic function, and that gene knockdown in CTb cells is a relevant tool to study DS-related dysfunction.

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OBJECTIVE: To establish the absence of adrenal suppression of fluticasone propionate (FP) 0.05% lotion when applied extensively to children (3 months to 6 years), with moderate to severe atopic dermatitis (AD). STUDY DESIGN: Open-label, conducted at 6 US centers; 44 subjects (3 to 71 months) with widespread AD (mean body surface area treated, 65%) received FP lotion twice daily for up to 4 weeks. RESULTS: No significant differences in mean cortisol levels were detected before or after treatment. At baseline, mean (+/-standard deviation) cortisols before and after cosyntropin (CST) stimulation were 13 +/- 6 microg/dL and 35 +/- 6 microg/dL, respectively. End-treatment, pre-CST, and post-CST cortisols were 12 +/- 6 microg/dL and 33 +/- 8 microg/dL, respectively. All 42 subjects with end-treatment post-CST cortisols demonstrated a normal adrenal response to CST (>18.0 microg/dL). FP lotion was well tolerated. Subjects who had blood drawn for bioavailability showed no correlation between FP levels and end-treatment post-CST cortisols. CONCLUSIONS: In patients as young as 3 months, FP lotion had no effect on HPA axis function and did not cause skin thinning even when used extensively over widespread, severe inflammatory disease. These results, together with others from studies using cream and ointment, provide further evidence of the safety of FP.

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Down syndrome (DS) in humans, or trisomy of autosome 21, represents the hyperdiploidy that most frequently survives gestation, reaching an incidence of 1 in 700 live births. The condition is associated with multisystemic anomalies, including those affecting the central nervous system (CNS), determining a characteristic mental retardation. At a neuronal level, our group and others have shown that the condition determines marked alterations of action potential and ionic current kinetics, which may underlie abnormal processing of information by the CNS. Since the use of human tissue presents both practical and ethical problems, animal models of the human condition have been sought. Murine trisomy 16 (Ts16) is a model of the human condition, due to the great homology between human autosome 21 and murine 16. Both conditions share the same alterations of electrical membrane properties. However, the murine Ts16 condition is unviable (animals die in utero), thus limiting the quantity of tissue procurable. To overcome this obstacle, we have established immortal cell lines from normal and Ts16 mice with a method developed by our group that allows the stable in vitro immortalization of mammalian tissue, yielding cell lines which retain the characteristics of the originating cells. Cell lines derived from cerebral cortex, hippocampus, spinal cord and dorsal root ganglion of Ts16 animals show alterations of intracellular Ca2+ signals in response to several neurotransmitters (glutamate, acetylcholine, and GABA). Gene overdose most likely underlies these alterations in cell function, and the identification of the relative contribution of DS associated genes on such specific neuronal dysfunction should be investigated. This could enlighten our understanding on the contribution of these genes in DS, and identify new therapeutic targets.

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OBJECTIVES: To characterize Wisconsin-born infants with 21-hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH) who were not identified by the newborn screening for 21-OH-D-CAH, and to examine male and female screening 17-hydroxyprogesterone (17-OHP) levels. STUDY DESIGN: Information on infants with false-negative results was gathered. Results of the Wisconsin newborn screening for 21-OH-D-CAH from January 1, 2000, to June 30, 2003, were analyzed to detect possible differences between male (n=119,842) and female (n=114,951) infants. RESULTS: Six of 7 female infants with false-negative results had genital masculinization, and 4 of 8 infants with false-negative results had laboratory evidence of salt-wasting. None died, had a salt-wasting crisis, or was assigned the wrong sex. A significant difference in the mean 17-OHP levels between male (17.5 ng/mL) and female (15.4 ng/mL) infants (P <.0001) was detected. The sensitivity of newborn screening for female infants was 60%, compared with 80% for male infants. CONCLUSIONS: Male and female infants have significantly different mean 17-OHP levels on newborn screening, and female infants comprise most of the infants with false-negative results. Although health professionals should not assume that newborn screening for 21-OH-D-CAH is a means of identifying all affected infants, the primary goals of newborn screening for CAH (prevention of salt-wasting crises and sex misassignment) are fulfilled.

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