Breastfeeding, growth, and lung disease in the first 3 years of life in children with cystic fibrosis.

Background: The 2009 cystic fibrosis (CF) infant care guidelines recommend breastmilk as the initial feeding but do not address if/when it should be fortified or supplemented with formula to promote optimal growth and pulmonary health.

Methods: We conducted a prospective multi-center cohort study in breastfed and formula-fed infants that included 172 infants with CF who were born during 2012-17, enrolled after newborn screening at age 1.9 ± 1.

Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis.

Vitamin D sufficiency has been difficult to achieve consistently in patients with cystic fibrosis (CF), even with robust oral supplements. To assess vitamin D status and resistance to supplementation, we studied 80 adults using 25-hydroxyvitamin D (25OHD) determinations and whole genome sequencing to construct polygenic risk scores (PRS) that aggregate variants associated with vitamin D status. The results revealed that 30 % of patients were below the threshold of 30 ng/mL and thus should be regarded as insufficient despite normal vitamin E status, a reflection of adherence to fat soluble vitamin supplementation.

Impact of intrinsic and extrinsic risk factors on early-onset lung disease in cystic fibrosis.

Background: Although respiratory pathology is known to develop in young children with cystic fibrosis (CF), the determinants of early-onset lung disease have not been elucidated.

Objective: We aimed to determine the impact of potential intrinsic and extrinsic risk factors during the first 3 years of life, testing the hypothesis that both contribute significantly to early-onset CF lung disease.

Design: We studied 104 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and evaluated comprehensively to 36 months of age.

Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements.

Background & Aims: Children with cystic fibrosis (CF) are susceptible to fat-soluble vitamin deficiencies unless supplemented, but even large doses of vitamin D may not prevent low 25-hydroxyvitamin D (25OHD) concentrations. The explanation for these vitamin D non-responders has been elusive. We utilized data from whole genome sequencing (WGS) to test the hypothesis that genetic variations predict responsiveness to vitamin D supplementation in a prospective cohort study of children with CF in the first 3 years of life.

Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics.

Background: Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed.

Objective: To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life.

Design: We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age.

Vitamins A, D, E status as related to supplementation and lung disease markers in young children with cystic fibrosis.

Background: The variable response to fat-soluble vitamin supplementation in young children with cystic fibrosis (CF), and factors contributing to this variability, remain under-investigated.

Objective: To determine if recommended supplement doses normalize serum vitamins A (retinol), D (25-hydroxy-vitamin D, 25OHD), and E (α-tocopherol), and identify factors predictive of achieving sufficiency, in children with CF in the first 3 years of life.

Design: We studied 144 infants born during 2012-2017 and diagnosed with CF through newborn screening.

Assessing the Reproducibility of Microbiome Measurements Based on Concordance Correlation Coefficients.

Evaluating the reproducibility or agreement of microbiome measurements is often a crucial step to ensure rigorous downstream analyses in microbiome studies. In this paper, we address this need by developing adaptations of Lin's concordance correlation coefficient (CCC) tailored to microbiome studies. We introduce a general formulation of the new CCC measures upon the use of a distance function appropriately characterizing the discrepancy between microbiome compositional measurements.

Zinc status and growth in infants and young children with cystic fibrosis.

Background: Zinc deficiency is associated with poor growth in children without cystic fibrosis (CF), but its impact on growth in children with CF is unknown.

Objective: To determine the prevalence of low serum Zn (sZn) and its relationship with growth in the first 3 years of life in children with CF.

Methods: We utilized data from infants with CF who were enrolled in a longitudinal study of nutrition and lung health and had sZn measured as part of clinical care.

GENERALIZED ACCELERATED RECURRENCE TIME MODEL IN THE PRESENCE OF A DEPENDENT TERMINAL EVENT.

Recurrent events are commonly encountered in longitudinal studies. The observation of recurrent events is often stopped by a dependent terminal event in practice. For this data scenario, we propose two sensible adaptations of the generalized accelerated recurrence time (GART) model (Sun et al.

Generalized accelerated recurrence time model for multivariate recurrent event data with missing event type.

Recurrent events data are frequently encountered in biomedical follow-up studies. The generalized accelerated recurrence time (GART) model (Sun et al., 2016), which formulates covariate effects on the time scale of the mean function of recurrent events (i.

Early life growth patterns persist for 12 years and impact pulmonary outcomes in cystic fibrosis.

Background: In children with cystic fibrosis (CF), recovery from growth faltering within 2 years of diagnosis (Responders) is associated with better growth and less lung disease at age 6 years. This study examined whether these benefits are sustained through 12 years of age.

Methods: Longitudinal growth from 76 children with CF enrolled in the Wisconsin CF Neonatal Screening Project was examined and categorized into 5 groups: R, R, and R, representing Responders who maintained growth improvement to age 12, 6, and 2 years, respectively, and I and N representing Non-responders whose growth did and did not improve during ages 2-6 years, respectively.

Serum carotenoid interactions in premenopausal women reveal α-carotene is negatively impacted by body fat.

Increasing body mass indices (BMIs) across the globe reflect pandemic shifts towards habitual positive energy imbalances. Excess body fat in individuals is often associated with high-energy and high-fat diets scanty in fresh produce. Carotenoids are fat-soluble pigments plentiful in many fruits and vegetables.

Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data.

Background: Persistent Pseudomonas aeruginosa (PPA) infection promotes lung function deterioration in children with cystic fibrosis (CF). Although early CF diagnosis through newborn screening (NBS) has been shown to provide nutritional/growth benefit, it is unclear whether NBS lowers the risk of PPA infection and how the effect of NBS vary with age. Modeling the onset age of PPA infection is challenging because 1) the onset age of PPA infection is interval censored in patient registry data; and 2) some risk factors such as NBS may have time-varying effects.

Pubertal Height Growth and Adult Height in Cystic Fibrosis After Newborn Screening.

Background: To examine long-term growth benefit of newborn screening (NBS), adolescent peak height velocity (PHV), and adult height were compared between the screened (diagnosed early via NBS) and the control (identified generally by symptoms) in the Wisconsin Randomized Clinical Trial.

Methods: Data from 107 children born in 1985-1994 and followed through 2012 were analyzed. PHV was estimated by a semiparametric growth curve model and compared with Tanner reference.

Generalizing Quantile Regression for Counting Processes with Applications to Recurrent Events.

In survival analysis, quantile regression has become a useful approach to account for covariate effects on the distribution of an event time of interest. In this paper, we discuss how quantile regression can be extended to model counting processes, and thus lead to a broader regression framework for survival data. We specifically investigate the proposed modeling of counting processes for recurrent events data.

Nonparametric association analysis of bivariate left-truncated competing risks data.

We develop time-varying association analyses for onset ages of two lung infections to address the statistical challenges in utilizing registry data where onset ages are left-truncated by ages of entry and competing-risk censored by deaths. Two types of association estimators are proposed based on conditional cause-specific hazard function and cumulative incidence function that are adapted from unconditional quantities to handle left truncation. Asymptotic properties of the estimators are established by using the empirical process techniques.

Association Between Alcohol Use Among College Students and Alcohol Outlet Proximity and Densities.

Background: Alcohol consumption is common on college campuses and is associated with negative consequences. Factors associated with availability of alcohol are not completely understood.

Objective: To describe how proximity and density of alcohol outlets are associated with any drinking and binge drinking in students at the University of Wisconsin-Madison.

Comparing the Use of Centers for Disease Control and Prevention and World Health Organization Growth Charts in Children with Cystic Fibrosis through 2 Years of Age.

Objective: To examine differences between use of World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) growth reference in children with cystic fibrosis (CF) up to 2 years of age.

Study Design: Growth from 1-24 months in 2587 children, born 2003-2006 and recorded in the US CF Foundation Registry, was evaluated using WHO and CDC references.

Results: In both boys and girls with CF aged 1-24 months, use of WHO charts resulted in ∼8 percentile lower length-for-age and ∼13% higher short stature rate (length-for-age <5th percentile).

Pubertal height velocity and associations with prepubertal and adult heights in cystic fibrosis.

Objectives: To test the hypothesis that pubertal peak height velocity (PHV) in cystic fibrosis (CF) has improved and is influenced by prepubertal growth and genetic potential.

Study Design: PHV from 1862 children born in 1984-87 and documented in the 1986-2008 US CF Foundation Registry was determined by statistical modeling and classified into normal, delayed (2-SD > average age), attenuated (magnitude <5th percentile), or both delayed and attenuated (D&A). Genetic potential for height was estimated by parental stature.

Nutritional status is associated with health-related quality of life in children with cystic fibrosis aged 9-19 years.

Background: The impact of improved nutritional status on health-related quality of life (HRQOL) is unknown for children with cystic fibrosis (CF).

Methods: Associations between nutritional status and HRQOL were examined over 2 years in 95 children, aged 9-19 years, who were followed in the Wisconsin Newborn Screening Project. HRQOL was assessed using the Cystic Fibrosis Questionnaire (CFQ).

Quantile regression for doubly censored data.

Double censoring often occurs in registry studies when left censoring is present in addition to right censoring. In this work, we propose a new analysis strategy for such doubly censored data by adopting a quantile regression model. We develop computationally simple estimation and inference procedures by appropriately using the embedded martingale structure.

Growth and pulmonary outcomes during the first 2 y of life of breastfed and formula-fed infants diagnosed with cystic fibrosis through the Wisconsin Routine Newborn Screening Program.

Background: The optimal feeding (breast milk, formula, or a combination) for infants with cystic fibrosis (CF) is unknown. Recommendations from the CF Foundation are based on limited data.

Objective: We compared growth and pulmonary outcomes between breastfed and formula-fed infants through the age of 2 y.

Cytosol-localized heat shock factor-binding protein, AtHSBP, functions as a negative regulator of heat shock response by translocation to the nucleus and is required for seed development in Arabidopsis.

Heat shock response (HSR) is a universal mechanism in all organisms. It is under tight regulation by heat shock factors (HSFs) and heat shock proteins (HSPs) after heat shock (HS) to prevent stress damage. On the attenuation of HSR, HSP70 and HSF Binding Protein1 (HSBP1) interact with HSF1 and thus dissociate trimeric HSF1 into an inert monomeric form in humans.

Strategies to increase vegetable or reduce energy and fat intake induce weight loss in adults.

For obese individuals seeking to optimize health and well-being, healthy dietary strategies are important. Vegetables and fruits contribute to a healthy diet, and increased consumption may cause weight reduction by displacing foods high in energy and fat. The objective of this study was to determine if advising high vegetable (8 servings) and moderate fruit (2-3 servings) consumption would result in weight reduction in obese individuals.