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Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive muscular atrophy and weakness. The primary cause of morbidity and mortality in these children is pulmonary disease due to poor airway clearance that leads to acute respiratory failure. There is a paucity of literature on the treatment of children with SMA and acute respiratory failure.We performed a retrospective chart review of pediatric patients with SMA type I or II admitted to the PICU in a tertiary-care children's hospital with acute respiratory failure who required mechanical ventilation and/or aggressive airway clearance.The study included 300 unique encounters among 137 unique subjects. All the subjects received airway clearance at home before admission, and 257 encounters (85.7%) were supported with noninvasive ventilation (NIV) before admission. Sixty-eight subjects (49.6%) required endotracheal intubation on admission or at some point during their PICU stay. The median (interquartile range [IQR]) time to intubation was 0 (0-20) h, and the median (IQR) duration of mechanical ventilation was 2 (1-5) d on invasive mechanical ventilation with no statistical difference between type I and type II (The subjects with SMA types I or II can be treated successfully with NIV and aggressive airway clearance during acute respiratory failure. Similarly, when intubation is required, successful extubation can be achieved with NIV transitional support combined with aggressive airway clearance maneuvers.

Polymethine fluorophores have facilitated the advance of biological and material sciences, due to their advantageous photophysical properties. However, the need to maintain a monomeric state can severely limit the utility and processability of dyes. High concentrations of fluorophore can lead to aggregation and negate the beneficial photophysical properties of monomers. Another concern is “crossing the cyanine limit” in which delocalization within the polymethine scaffold is broken, producing the presence of an asymmetric state diminishing its photophysical behavior. Herein, we attempt to overcome these limitations by exploring anion exchange on a cationic flavylium heptamethine scaffold. By increasing the size and hydrophobicity of the anion, we can effectively tune the degree of ion pairing within the polymethine dye. Interestingly, we found that the effect of ion pairing on photophysical properties was subtle for the flavylium heptamethine scaffold in comparison to the more commonly used indolenine cyanine dye. Utilizing larger weakly coordinating anions enabled solubility of the flavylium heptamethine fluorophore in nonpolar solvents, which could otherwise not be achieved. Even with more subtle effects than classic cyanine dyes, anion exchange on flavylium polymethine dyes holds potential for further manipulation of the properties of these low energy dyes.

An efficient and simple approach for stereoselective synthesis of β-Kdo C-glycosides was described, which relies on easily available peracetylated anomeric acetate or anomeric 2-pyridyl sulfide to couple with carbonyl compounds via SmI2-mediated Reformatsky reactions. The utility of this methodology is exemplified by the streamlined synthesis of a practical β-Kdo C-glycoside with an anomeric aminopropyl linker to conjugate with other biomolecules for further biological studies.

A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described. A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations. The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.

ImportanceThe prevalence of obesity among youths 2 to 19 years of age in the US from 2017 to 2018 was 19.3%; previous studies suggested that school lunch consumption was associated with increased obesity. The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) strengthened nutritional standards of school-based meals.ObjectiveTo evaluate the association between the HHFKA and youth body mass index (BMI).Design, Setting, and ParticipantsThis cohort study was conducted using data from the Environmental Influences on Child Health Outcomes program, a nationwide consortium of child cohort studies, between January 2005 and March 2020. Cohorts in the US of youths aged 5 to 18 years with reported height and weight measurements were included.ExposuresFull implementation of the HHFKA.Main Outcomes and MeasuresThe main outcome was annual BMI z-score (BMIz) trends before (January 2005 to August 2016) and after (September 2016 to March 2020) implementation of the HHFKA, adjusted for self-reported race, ethnicity, maternal education, and cohort group. An interrupted time-series analysis design was used to fit generalized estimating equation regression models.ResultsA total of 14 121 school-aged youths (7237 [51.3%] male; mean [SD] age at first measurement, 8.8 [3.6] years) contributing 26 205 BMI measurements were included in the study. Overall, a significant decrease was observed in the annual BMIz in the period following implementation of the HHFKA compared with prior to implementation (−0.041; 95% CI, −0.066 to −0.016). In interaction models to evaluate subgroup associations, similar trends were observed among youths 12 to 18 years of age (−0.045; 95% CI, −0.071 to −0.018) and among youths living in households with a lower annual income (−0.038; 95% CI, −0.063 to −0.013).Conclusions and RelevanceIn this cohort study, HHFKA implementation was associated with a significant decrease in BMIz among school-aged youths in the US. The findings suggest that school meal programs represent a key opportunity for interventions to combat the childhood obesity epidemic given the high rates of program participation and the proportion of total calories consumed through school-based meals.

A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2

TiO2 nanostructures that feature a two-dimensional (2D) morphology have attracted extensive attention in environment processing and energy conversion fields owing to their peculiarly large surface area and superior transfer efficiency of photogenerated carriers. In this work, we proposed a hybrid approach including a plasma electrolyte oxidation (PEO) and ion exchange strategy to in situ synthesize TiO2 nanosheets on a flexible Ti mesh substrate, in which the layered Na2Ti2O5 nanosheets were fabricated as a template. The TiO2 nanosheets are crystalline anatase phase and exhibit excellent photocatalytic activity and stability in removing phenol. With the modification of the Pt cocatalyst, the phenol degradation performance has been significantly enhanced. More importantly, the in situ grown TiO2 nanosheets on the flexible Ti mesh provide strong substrate adhesion that enables superior photocatalytic stability for cyclic degradation of phenol. It can be expected that the synthetic strategy proposed in this work can pave a solid way toward the in situ growth of various TiO2-based composite nanophotocatalysts with sufficient active sites and excellent photocatalytic properties, and thus, it will open up more opportunities for environment processing and energy conversion.

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 (J. Amer. Statist. Assoc. 111 (2016) 145–156) to provide useful alternative analyses that can offer physical interpretations while rendering extra flexibility beyond the existing work based on the accelerated failure time model. Our modeling strategies align with the rationale underlying the use of the survivors’ rate function or the adjusted rate function to account for the presence of the dependent terminal event. For the proposed models, we identify and develop estimation and inference procedures which can be readily implemented based on existing software. We establish the asymptotic properties of the new estimator. Simulation studies demonstrate good finite-sample performance of the proposed methods. An application to a dataset from the Cystic Fibrosis Foundation Patient Registry (CFFPR) illustrates the practical utility of the new methods.

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.e., time to expected frequency), has arisen as a useful secondary analysis tool to provide meaningful physical interpretations. In this article, we investigate the GART model in a multivariate recurrent events setting, where subjects may experience multiple types of recurrent events and some event types may be missing. We propose methods for the GART model that utilize the inverse probability weighting technique or the estimating equation projection strategy to handle event types that are missing at random. The new methods do not require imposing any parametric model for the missing mechanism, and thus are robust; moreover, they enjoy easy and stable implementation. We establish the uniform consistency and weak convergence of the resulting estimators and develop appropriate inferential procedures. Extensive simulation studies and an application to a dataset from Cystic Fibrosis Foundation Patient Registry (CFFPR) illustrate the validity and practical utility of the proposed methods.

Early phase chemoprevention trials are designed to demonstrate safety, tolerability, feasibility, and signals of efficacy. Yet it is often observed that most trials fail to detect intervention effects. The purpose of this review was to analyze intervention effects in such trials by comparing planned vs observed effect sizes. Single or multi-arm efficacy and biomarker chemoprevention trials conducted under the Phase 0-II Cancer Prevention Clinical Trial Program of the Division of Cancer Prevention, National Cancer Institute between 2003 and 2019 were evaluated. Protocols were reviewed to gather information regarding study design, primary endpoint(s), analysis plan, analysis population(s), and sample size justifications with planned effect sizes. Reports and manuscripts were reviewed to obtain study results information. Intervention effects for differences were quantified by calculating standardized Cohen's d effect sizes. In studies where only p-values were reported without effect sizes, observed effect sizes were estimated using p-values and sample size information. Planned effect sizes were compared to observed effect sizes and post-hoc power calculations were conducted. Of a total of 59 trials reviewed, twenty-four trials were efficacy or biomarker studies with complete information on planned and observed effect sizes. Organ sites of focus included 5 (21%) breast, 6 (25%) prostate, 4 (17%) lung, and 9 (38%) gastrointestinal and other sites. The majority of the trials (n=18) were multi-arm randomized studies of which 15 trials were blinded. The median planned effect size for detecting an intervention effect was 0.75 (range 0.2-1.14), while the median planned sample size per arm was n=30 (range 11-101). The planned effect sizes were larger than the observed effects sizes in the majority of the studies (88%). The observed effect sizes in most studies were small with a median of 0.34 (range 0-0.66). The median difference between planned vs observed effect size was -0.37. A low level of concordance between planned vs observed effect size was observed with an intra-class correlation coefficient 0.18 (95% CI: -0.1-0.50). The median post-hoc power for detecting the observed effect sizes was only 0.29 (range 0.03-0.93). There were no significant differences detected between planned vs observed effect sizes when stratified by accrual goals, analysis populations, or study design (multi-arm randomized vs single arm). The results indicate that the majority of early phase chemoprevention trials have much smaller observed effect sizes than planned. Sample size calculations for such trials need to balance the known attributes of the study endpoints, e.g. the potential detectable effect sizes in populations that can be realistically and cost-effectively accrued, with the need to detect only effect sizes large enough to justify subsequent phase III trials. Utilization of interim analyses for futility may be considered. Citation Format: Jens C. Eickhoff, Jen Birstler, Guanhua Chen, Zhumin Zhang, Vikrant Sahasrabuddhe, Eva Szabo, KyungMann Kim. Planned versus observed effect sizes in early phase chemoprevention trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 110.

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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.e., time to expected frequency), has arisen as a useful secondary analysis tool to provide meaningful physical interpretations. In this article, we investigate the GART model in a multivariate recurrent events setting, where subjects may experience multiple types of recurrent events and some event types may be missing. We propose methods for the GART model that utilize the inverse probability weighting technique or the estimating equation projection strategy to handle event types that are missing at random. The new methods do not require imposing any parametric model for the missing mechanism, and thus are robust; moreover, they enjoy easy and stable implementation. We establish the uniform consistency and weak convergence of the resulting estimators and develop appropriate inferential procedures. Extensive simulation studies and an application to a dataset from Cystic Fibrosis Foundation Patient Registry (CFFPR) illustrate the validity and practical utility of the proposed methods.

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. Our simulation study shows that the estimators perform well with moderate sample sizes. We apply our methods to the Cystic Fibrosis Foundation Registry data to study the relationship between onset ages of Pseudomonas aeruginosa and Staphylococcus aureus infections.

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 Conclusions Growth status in children with CF differed when using WHO and CDC references, particularly during the second year of life. These differences need to be considered for all uses of growth assessment in CF.

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 12 , R 6 , and R 2 , representing Responders who maintained growth improvement to age 12, 6, and 2 years, respectively, and I 6 and N 6, representing Non-responders whose growth did and did not improve during ages 2–6 years, respectively. Lung disease was evaluated by % predicted forced expiratory volume in one second (FEV 1 ) and chest radiograph (CXR) scores. Results Sixty-two percent were Responders. Within this group, 47% were R 12 , 28% were R 6 , and 25% were R 2 . Among Non-responders, 76% were N 6 . CF children with meconium ileus (MI) had worse lung function and CXR scores compared to other CF children. Among 53 children with pancreatic insufficiency without MI, R 12 had significantly better FEV 1 (97–99% predicted) and CXR scores during ages 6–12 years than N 6 (89–93% predicted). Both R 6 and R 2 experienced a decline in FEV 1 by ages 10–12 years. Conclusions Early growth recovery in CF is critical, as malnutrition during infancy tends to persist and catch-up growth after age 2 years is difficult. The longer adequate growth was maintained after early growth recovery, the better the pulmonary outcomes at age 12 years.

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. They are well-known for provitamin A and antioxidant functions, but little research has been done related to carotenoid-body mass interactions. Serum carotenoids were analyzed relative to body fat to determine correlations between major serum carotenoids, retinol, BMI, fat mass, and lean mass. Healthy women ( n = 76), 19–50 years old, were categorized into two comparison groups determined by percent body fat measured by air displacement plethysomography (BOD POD®), i.e. 0.05). Dietary intake between groups did not differ, including carrot consumption (a high dietary source of α-carotene). These results confirm previous carotenoid-health research and propose the need for further investigation of potential protective roles that α-carotene may perform for optimal health. Serum α-carotene may provide a deeper and clinically relevant purpose, beyond previous suggestions for its use as a biomarker for fruit and vegetable consumption, in that α-carotene may be a biomarker for chronic disease risk frequently linked with obesity. Impact statement Carotenoids are important pigments in fruit and vegetables and found in human serum. This study isolated a negative relationship between serum α-carotene and body fatness. As humans begin to live over a century, determining biomarkers of ultimate health is important. α-Carotene does not have the same distribution in the food supply as β-carotene and therefore is often overlooked in surveys. In part, this is due to the fact that β-carotene provides two molecules of vitamin A, while α-carotene provides one upon central cleavage. This study shows a very clear association between α-carotene and body fatness, which appears to go beyond its fat-soluble nature. Dietary intake data were not able to explain the association. Further work is needed to determine what dietary components infer health benefits.

Cystic fibrosis (CF) is a life-shortening genetic disorder characterized by malnutrition and lung disease. In the United States, approximately 30,000 individuals live with CF, and approximately 1000 infants are born with CF every year. In 2009, the median age of survival for patients with CF was 36 years. The primary method of diagnosis for CF has transitioned from the traditional method using signs and symptoms prior to 2004 to nationwide newborn screening. Malnutrition in CF is caused by increased losses from maldigestion/malabsorption due primarily to pancreatic insufficiency, increased requirement from increased energy expenditure associated with pulmonary infection, and decreased intake from poor appetite associated with CF complications. Nutritional therapy for CF patients focuses on a high-caloric, high-fat diet combined with pancreatic enzyme therapy, with the goal of promoting normal growth for children and normal weight status for adults. Guidelines for nutritional assessment and management of CF patients are presented in this chapter.

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. Methods This problem fits into the framework of a recently developed Bayesian dynamic Cox model for interval censored data, where each regression coefficient is allowed to be time-varying to an extent determined by the data. Results Application of the methodology to data from the CF Foundation Patient Registry revealed interesting findings. Compared with patients with meconium ileus or diagnosed through signs or symptoms, patients diagnosed through NBS had significantly lower risks of acquiring PPA infection between age 1 and 2 years, and the benefit in survival rate was found to last up to age 4 years. Two cohorts of five years apart were compared. Patients born in cohort 2003–2004 had significantly lower risks of the PPA infections at any age up to 4 years than those born in 1998–1999. Conclusions The study supports benefits of NBS on PPA infection in early childhood. In addition, our analyses demonstrate that patients in the more recent cohort had significantly lower risks of acquiring PPA infection up to age 4 years, which suggests improved CF treatment and care over time. Electronic supplementary material The online version of this article (doi:10.1186/s12874-016-0220-5) contains supplementary material, which is available to authorized users.

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.RESULTS:Meconium ileus (MI; n = 25) was associated with the worst pubertal growth and adult height, including 1 child who did not experience apparent PHV; children with pancreatic sufficiency (n = 18) achieved the best growth (normal PHV and adult height). In children with pancreatic insufficiency without meconium ileus (n = 64), the subgroup most likely to benefit from NBS, screened children had similar PHV but better adult height compared with controls. Specifically, in boys, the screened group (n = 22) achieved normal PHV (9.5 cm at 13.5 years); the control group (n = 19) had similar onset age (13.6 years) but 0.6-cm lower magnitude (P = .08). In girls, the screened group (n = 10) had somewhat later (12.5 years vs 11.7 years, P = .12) and lower PHV (7.3 cm vs 7.9 cm, P = .33) than the controls (n = 13), coinciding with later menarche (13.6 years vs 12.2 years, P = .10). Adult height was taller in the screened than the control (50th vs 29th percentile, P = .02), even after adjusted for genetic potential (32nd vs15th percentile, P = .006). Differences in adult height were primarily attributable to NBS and better prepubertal growth.CONCLUSIONS:Early linear growth benefits of NBS were sustained through puberty, leading to better adult height in cystic fibrosis.

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. Design: A total of 103 CF infants born in 1994–2006 and diagnosed through newborn screening in Wisconsin were studied. Breastfed infants were classified by the duration of exclusive breastfeeding (ExBF). Exclusive formula-feeding (ExFM) was classified by the formula's caloric density (ie, standard [0.67 kcal/mL (20 kcal/oz) (ExFM20)] throughout infancy or high density [≥0.74 kcal/mL (22 kcal/oz) (ExFM22+)] for some duration of infancy). Results: Fifty-three infants (51% of infants) were breastfed and 50 infants (49% of infants) were ExFM. In breastfed infants, the duration of ExBF was

Background Obesity has been proposed to be a risk factor for the development of childhood asthma. Objective We sought to examine weight status from birth to age 5 years in relation to the occurrence of asthma at ages 6 and 8 years. Methods Two hundred eighty-five full-term high-risk newborns with at least 1 asthmatic/atopic parent enrolled in the Childhood Origin of Asthma project were studied from birth to age 8 years. Overweight was defined by weight-for-length percentiles of greater than the 85th percentile before the age of 2 years and a body mass index percentile of greater than the 85th percentile at ages 2 to 5 years. Results No significant concurrent association was found between overweight status and wheezing/asthma occurrence at each year of age. In contrast, longitudinal analyses revealed complex relationships between being overweight and asthma. Being overweight at age 1 year was associated with a decreased risk of asthma at age 6 (odds ratio [OR], 0.32; P = .02) and 8 (OR, 0.35; P = .04) years, as well as better lung function. However, being overweight beyond infancy was not associated with asthma occurrence. In fact, only children who were overweight at age 5 years but not at age 1 year had an increased risk of asthma at age 6 years (OR, 5.78; P = .05). Conclusion In children genetically at high risk of asthma, being overweight at age 1 year was associated with a decreased risk of asthma and better lung function at ages 6 and 8 years. However, being overweight beyond infancy did not have any protective effect and even could confer a higher risk for asthma.

Objective Evaluate a theory-based, Internet-delivered nutrition education module. Design Randomized, treatment-control design with pre-post intervention assessments. Setting and Participants Convenience sample of 160 young adults (aged 18-24) recruited by community educators in 4 states. Study completers (n = 96) included a mix of racial/ethnic groups and family demographics, but were predominately white females without children. Intervention A Transtheoretical Model (TTM)-based, stage-tailored Internet program, FV controls received nontailored messages in a comparable format. Main Outcome Measures and Analysis TTM constructs at baseline, immediately postviewing, and at 30-day follow-up were compared via chi-square, McNemar's test, and logistic regression. Qualitative use and acceptability indicators were collected postviewing (treatment only). Results Of baseline respondents, 86.5% completed the study. At follow-up, self-efficacy, decisional balance, and selected processes improved for both groups, with only marginal advantages for the theory-based version. Fruit and vegetable consumption changes were similar for both groups. Qualitative measures of knowledge, confidence, and motivation improved (not measured for controls). Favorable ratings of treatment program acceptability and personal relevance were reported. Conclusions and Implications The Internet is a favorable option for reaching young adults with nutrition messages. This study did not identify strong advantages of theory-based tailoring, especially for fruit consumption, which had weaker barriers than vegetable consumption among this target audience.

Alcohol consumption is common on college campuses and is associated with negative consequences. Factors associated with availability of alcohol are not completely understood.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.Participants were full-time students enrolled in the Young Adults Eating and Active for Health, a multisite, randomized intervention that assessed a variety of health behaviors. Geographic information systems were used to calculate proximity and enumerate alcohol outlet densities. Participants were categorized as "drinkers" or "nondrinkers" based on self-reported alcohol consumption. Binge drinking was categorized as "non-binge drinker," "frequent binge drinker," and "excessive binge drinker." Analysis included regression, t tests, and chi-square tests. RESULTS. Among the 166 participants, 126 (76%) were drinkers. Among drinkers, 80 (63%) were either frequent or excessive binge drinkers. Drinkers lived closer to an alcohol outlet than non-drinkers (0.18 +/- 0.15 vs. 0.61 +/- 1.59 miles, respectively, P=0.005). Within a 1-mile walking radius, there were 47% more establishments for drinkers (153 +/- 47 compared to 104 +/- 55 outlets for nondrinkers, P0.0001). At distances of 0.10-0.25 and 0.25-0.50 miles, twice as many outlets were available to drinkers (19 +/- 19 and 43 +/- 25, respectively) compared to nondrinkers (7 +/- 11 and 20 +/- 22, respectively), P0.001. Proximity and density were hot associated with binge drinking frequency.Drinkers lived closer to alcohol outlets and had significantly more outlets available at a distance of up to 1 mile. Municipal and college administrators could consider limiting alcohol license distributions in municipalities with high alcohol consumption.

Background: The Cystic Fibrosis Foundation (CFF) recommends using the percentage of ideal body weight (%IBWCFF) and body mass index percentiles (BMIp) to assess weight-for-height status and to screen for malnutrition. Objective: The objective was to examine the agreement and discrepancy between the use of %IBWCFF and BMIp for screening malnutrition. Design: Data from 13 021 children reported to the 2000 CFF Patient Registry were analyzed. Results: In children of average stature (ie, height-for-age between the 25th and 75th percentiles) and aged 10 y, %IBWCFF corresponded closely to BMIp, and the prevalence of underweight estimated by %IBWCFF 90% was similar to that by BMIp 15th percentile. However, in children with short stature (ie, height-forage 25th percentile), %IBWCFF reflected significantly better weight-for-height status than did the BMIp, whereas the opposite trend was observed in children with tall stature (ie, height-for-age 75th percentile). Such discrepancies averaged 8 –12 percentage points when BMIp was reexpressed to the same unit and scale as %IBWCFF. Consequently, the prevalence of underweight estimated by %IBWCFF 90% was significantly lower (7.3%) than that estimated by BMIp 15th percentile (25.7%) in children with short stature, whereas the opposite trend was found in children with tall stature (47.7% and 14.4%, respectively). Additional analyses showed that BMIp was more sensitive to, and had stronger associations with, the percentage of predicted forced expiratory volume in 1 s. Conclusion: Compared with BMIp, %IBWCFF underestimated the severity of malnutrition in children with short stature and overestimated the severity of malnutrition in children with tall stature. Am J Clin Nutr 2004;80:982–91.

Section I: Basic Principles and Concepts Examining the Relationship between Diet, Nutrition and Disease: Dietary Assessment Methodology. Energy Requirement Methodology. Physical Assessment. Overview of Nutritional Epidemiology. Analysis, Presentation, and Interpretation of Dietary Data. Nutrition Intervention: Current Theoretical Bases for Nutrition Intervention and Their Uses. Nutrition Intervention: Lessons from Clinical Trials. Tools and Techniques to Facilitate Eating Behavior Change. Evaluation of Nutrition Interventions. Biomarkers and Biological Indicators of Change. Genetic Influence on Nutritional Health: Genetic Influences on Blood Lipids and Cardiovascular Disease Risk. Genetics of Human Obesity. Genetic Influence on Cancer Risk. Inborn Errors of Metabolism. Supplements and Food Replacements: Role of Liquid Dietary Supplements. Composite Foods and Formulas, Parenteral and Enteral Nutrition. Herbs and Other Botanical Supplements: Principles and Concepts. Section II: Disease-Specific Intervention: Prevention and Treatment Cardiovascular Disease: Dietary Macronutrients and Cardiovascular Risk. Other Dietary Components and Cardiovascular Risk. Nutrition, Diet & Hypertension. Nutrition and Congestive Heart Failure. Cancer Prevention and Therapy: Nutrition and Breast Cancer. Nutrition and Colon Cancer. Nutrition and Prostate Cancer. Nutrition and Lung Cancer. Nutrition and the Patient with Cancer. Diabetes Melitus: Obesity and the Risk for Diabetes. Nutrition Management for Type 1 Diabetes. Nutritional Management of Type 2 Diabetes. Nutrition Management for Gestational Diabetes. Obesity: Overview of Treatments and Interventions. Role of Physical Activity. Micronutrient Intake and Body Weight. Behavioral Risk Factors for Obesity: Diet and Physical Activity. Role of Taste and Appetite in Body Weight Regulation. Gastrointestinal Diseases: Nutrition in the Prevention and Treatment of Common Gastrointestinal Symptoms. Nutrient Considerations in Lactose Intolerance. Nutrient Considerations in Inflammatory Bowel Disease and Short Bowel Syndrome. Nutrition and Liver Disease. Other Major Diseases: Nutrition and Renal Disease. Nutritional Management of Parkinson's Disease and Other Conditions Like Alzheimer's Disease. Osteoporosis. Eating Disorders: Anorexia Nervosa, Bulimia Nervosa and Binge Eating Disorder. Nutrition and Food Allergy. Nutrition and Cystic Fibrosis. Osteomalacia. Nutrition and Immunodeficiency Syndromes. Disease Prevention Strategy: Nutrition Guidelines to Maintain Health. Epilogue.

Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.

ObjectiveThe 2002 Cystic Fibrosis Foundation (CFF) practice guidelines recommend adjusting for genetic potential when evaluating height status in children with CF. However, there is paucity of data to support this recommendation. We compared three methods of classifying short stature: unadjusted height percentile

The aim of this study was to detect the effect of interactions between single-nucleotide polymorphisms (SNPs) on incidence of heart diseases. For this purpose, 2912 subjects with 350,160 SNPs from the Framingham Heart Study (FHS) were analyzed. PLINK was used to control quality and to select the 10,000 most significant SNPs. A classification tree algorithm, Generalized, Unbiased, Interaction Detection and Estimation (GUIDE), was employed to build a classification tree to detect SNP-by-SNP interactions for the selected 10 k SNPs. The classes generated by GUIDE were reexamined by a generalized estimating equations (GEE) model with the empirical variance after accounting for potential familial correlation. Overall, 17 classes were generated based on the splitting criteria in GUIDE. The prevalence of coronary heart disease (CHD) in class 16 (determined by SNPs rs1894035, rs7955732, rs2212596, and rs1417507) was the lowest (0.23%). Compared to class 16, all other classes except for class 288 (prevalence of 1.2%) had a significantly greater risk when analyzed using GEE model. This suggests the interactions of SNPs on these node paths are significant.

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. We compared this to advising a more traditional strategy of reducing daily energy intake by 500 kcal (2.1 MJ)/d and limiting energy from fat to ≤25%. A randomized study design was used. Subjects (age 21–50 y, n = 30/group) received food (2 meals + 1 snack/d, 5 d/wk) and education (2 group lessons/wk plus individual consultations as requested) for the first 3 mo. Weight and body composition were measured at baseline and after 3, 12, and 18 mo. Fasting serum lipid panel, insulin, glucose, hematocrit, and C-reactive protein were measured at baseline, 3, and 12 mo. Both groups lost weight after 3 mo ( P = 0.0087 for high vegetable diet and P < 0.0001 for energy reduction diet), and the energy and fat reduction diet resulted in lower weight over time ( P < 0.0001, treatment effect). Total cholesterol and cholesterol:HDL decreased after 3 mo in both groups ( P ≤ 0.0061). Both strategies produced initial weight loss at 3 mo, but only the group following the caloric and fat reduction advice maintained weight loss at the 12- and 18-mo follow-up assessments. Nonetheless, the group following the high vegetable advice did not regain weight above baseline. In conclusion, traditional messages to reduce calories and fat are important, and increasing vegetable intake can assist individuals to maintain weight.

Antioxidant defenses may be compromised in osteoporotic women. Little is known about fruit and vegetable or carotenoid consumption among postmenopausal women. The primary carotenoids in human serum are alpha- and beta-carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin. This study investigated the interrelationships among serum carotenoid concentrations, fruit and vegetable intake, and osteoporosis in postmenopausal women (n = 59, 62.7 +/- 8.8 y). Bone density was assessed by dual energy x-ray absorptiometry and osteoporosis diagnosis was based upon T-scores. Serum samples (n = 53) and three-day diet records (n = 49) were analyzed. Logistic regression analyzed differences between carotenoids after adjusting for serum retinol; supplement usage; milk, yogurt, fruit, and vegetable intake; and body mass index (BMI). Pearson statistics correlated carotenoids with specific fruit or vegetable intake. Serum lycopene concentrations were lower in the osteoporosis group than controls (p = 0.03). Beta-cryptoxanthin intake was higher in the osteoporosis group (p = 0.0046). Total fruit and vegetable intakes were correlated with serum lycopene and beta-cryptoxanthin (p = 0.03, 0.006, respectively). Serum alpha-carotene concentration was associated with carrot intake, and zeaxanthin and beta-cryptoxanthin with lettuce intake. Carotenoids that may have beneficial skeletal effects are lower in women with osteoporosis. Research is needed to identify potential protective mechanisms or utilization of carotenoids during osteoporosis.

Background: Increases in energy substrate oxidation occur at different rates after an increase in either fat or carbohydrate intake. Adaptations to increased fat intake are relatively slow and are influenced by activity level. Objective: We tested the hypothesis that increased levels of daily activity,asinfluencedbyaddedexercise,wouldhaveagradedeffect ontherateofcompensatoryadjustmenttoashort-termhigh-fatdiet. Design:Dailytotalenergyexpenditureandmacronutrientoxidation weremeasuredat3physicalactivitylevels(PALs)byusingawholeroom indirect calorimeter in 10 adult women as they transitioned froma1-dlow-fat(30%ofenergy)controldiettoa4-dhigh-fat(50% of energy) diet. The 3 PALs (1.4, 1.6, and 1.8) were provided daily by increases in bicycle ergometer exercise time. Results: An increase in physical activity led to a greater increase in the nonprotein respiratory exchange ratio (0.047 0.02, 0.064 0.02, and 0.071 0.02; P 0.0001) and 24-h fat oxidation (113 24, 125 19, and 147 20 g/d; P 0.0001) for PALs of 1.4, 1.6, and 1.8, respectively, after the transition from the low-fat control diet to the high-fat diet. Random-effects analysis found a significant (P 0.003) relation between PAL and the compensatory fat oxidation response to a high-fat diet. Conclusions: Amounts of exercise consistent with the Institute of Medicine’s recommendations reduce the time required to match fat oxidation to a change in the percentage of fat in the diet. Because short-term consumption of high-fat diets is thought to contribute to excess fat accumulation, regular exercise should be protective and should help maintain a healthy body composition. Am J Clin Nutr 2007;85:109–16.

Objectives To determine if early growth benefit of NBS sustains to adulthood, we compared adolescent peak height velocity (PHV) between screened (diagnosed early via NBS) and control (identified by symptoms) groups in the Wisconsin RCT. Methods Data from 106 patients born in 1985–94 and followed through 2012 with the same care protocol were analyzed. Results Pancreatic sufficient patients (n = 18) achieved normal pubertal PHV and adult height at age 18 y ( th %tile). Meconium ileus patients (MI, n=25) had reduced PHV and shorter adult height at age 18 y (males: 34 th %tile; females: 17 th %tile). In non-MI patients who had pancreatic insufficiency (n = 64), boys in the screened group (n = 22) had normal and slightly higher PHV (9.5 cm/y at 13.5 y) than the control group (n = 29, 8.9 cm/y at 13.6 y), girls in the screened group (n = 13) had later and slightly lower PHV (7.3 cm/y at 12.5 y) compared to control group (n = 11, 7.9 cm/y at 11.7 y), but the lower PHV in screened girls coincided with later menarche (13.6 y vs. 12.2 y) and was compensated by longer duration of pre-pubertal growth. Thus, adult heights at age 18 y in both sexes were taller in screened compared to control (50 th vs. 29 th %tile, p=0.025), which remained significant after adjusting for parental height (32 nd vs 15 th %tile, p=0.003). Multiple regression analysis revealed that the taller adult height in the screened group was primarily due to achievement of better pre-pubertal height (e.g., 47 th vs. 27 th percentile at age 7 y) rather than greater adolescent PHV. Conclusion This longest duration cohort study shows that early diagnosis/care can promote better long term growth and is a sustained benefit of NBS.

Objective NBS for CF became universal in the USA in 2010. To identify optimal feeding for CF infants, a multi-center prospective study known as FIRST (Feeding Infants Right … from the STart) was initiated in 2012 to enroll 160 infants by 2016 at 5 CF Centers (Madison and Milwaukee, WI; Indianapolis, IN; Salt Lake City, UT; and Boston, MA). Method Nutritional status in the first year of life from 91 infants (52% boys) enrolled at 1.4±0.6 mo to FIRST was assessed biochemically and anthropometrically. By 31/12/14, 80 infants were 6 mo and 60 infants were 12 mo old. Result Growth was normal at birth [3210±505 g (41 st %tile) and 50.1±2.8 cm (63 rd %tile)] but declined to the 18 th %tile at age 2 mo. Catch-up growth was observed; weight increased to 33 rd %tile at 6 mo and 64 th %tile at 12 mo, but length did not fully recover at 12 mo (44 th %tile). At birth, 73% were breastfed: 65% exclusive (exB) and 8% combined with formula (B&F). The rate of exB decreased to 41% by 1 mo and 16% by 6 mo, while B&F and exF increased to 27% and 57%, respectively, at 6 mo. In the first 6 mo of life, 60% of infants received fortified breast milk or high caloric density formula (22–30 kcal/oz). Abnormal essential fatty acid status was common before age 3 mo with 18% deficient [triene-tetraene (T/T) ratio >0.02] and another 18% insufficient (T/T ratio >0.01). Low vitamin D [25(OH)D Conclusion This new infant study shows that early diagnosis/care leads to substantial catch-up growth but biochemical nutritional status remains suboptimal. (Funded by NIH/CFF).

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.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-SDaverage age), attenuated (magnitude5th percentile), or both delayed and attenuated (DA). Genetic potential for height was estimated by parental stature.PHV averaged 8.4 cm/year at age 14.0 years in boys and 7.0 cm/year at age 12.1 years in girls, ∼6-month delay and ∼15% reduction compared with healthy children. PHV was normal in 60%, delayed in 9%, attenuated in 21%, and DA in 5%. Patients with delayed PHV reached similar adult height percentile (boys: 34th, girls: 46th) to those with normal PHV (boys: 33rd, girls: 34th); both were significantly taller than the attenuated (boys: 11th, girls: 19th) and DA PHV subgroups (boys: 8th, girls: 14th). Pancreatic-sufficient patients had taller prepubertal and adult heights but similar PHV compared with pancreatic-insufficient or meconium ileus patients. Adjusting for genetic potential reduced adult height percentiles more in boys (from 25th to 16th) than girls (from 28th to 24th). Height at age 7 years, PHV age and magnitude, and parental stature significantly predicted adult height.Pubertal PHV has improved in children with CF born after mid-1980s compared with older cohorts but remains below normal. Suboptimal prepubertal and pubertal growth led to adult height below genetic potential in CF.

Background: Individuals who focused on calorie counting lost more weight than those who focused on increasing vegetable and fruit (V&F) intake in a weight loss program. We now present serum carotenoid data (biomarkers of V&F intake) from both groups and test whether these biomarkers correlate with changes in weight and body fat. Design: Sixty obese volunteers were randomized to one of the following weight loss programs: 500 kcal per day reduction (Reduction) or a focus on consuming eight vegetables per day and 2–3 fruits per day (HiVeg). Volunteers in the Reduction group were 36.8±10.3 years with a body mass index of 33.5; 83% were white, 17% chose not to report race; 70% were not Hispanic or Latino, 13% were Hispanic or Latino and 17% chose not to report ethnicity. Volunteers in the HiVeg group were 30.4±6.6 years with a body mass index of 33.2: 74% white, 11% Asian, 5% black or African American, 5% multiracial and 5% chose not to report race; 89% were not Hispanic or Latino, 5% were Hispanic or Latino and 5% chose not to report ethnicity. Subjects were taught basic nutrition principles, received breakfast and lunch 5 days per week for 3 months, meals 2 days per week during month 4, then regular phone calls to month 12. Results: Total serum carotenoid concentrations increased from baseline to 3 months and remained elevated at 12 months, but there was no difference between groups. Changes in weight, fat and % fat correlated negatively with serum carotenoid concentrations. Conclusion: Increased serum carotenoids (a biomarker for V&F intake) correlated with improved weight and fat loss indicating that increased V&F consumption is an appropriate strategy for weight loss. However, in light of the fact that the Reduction group lost more weight, the consumption of increased V&F for the purpose of weight loss should happen within the context of reducing total caloric intake.