Understanding type and quality of relationships between individuals with chromosome 18 syndromes and their siblings.

Siblings of individuals with disabilities hold a pivotal and sometimes unappreciated position in the lives of their brother or sister. We sought to understand the unique challenges and opportunities in relationships between children with chromosome 18 conditions and their siblings and to identify the ways to support this relationship. Participants were recruited through the lay advocacy organization, the Chromosome 18 Registry & Research Society. Fifty-seven siblings from 36 families participated, using an investigator designed instrument, were asked to agree or disagreed with statements from four content areas (information and knowledge about the syndrome, feelings about the sibling relationship, involvement with and caregiving for their sibling, and support and advocacy). Siblings reported that they know their sibling with a disability very well and reported a wide range of emotions regarding their sibling. There was a strong sense of pride in their brother/sister's abilities, and many participants reported attempts to help others understand their brother/sister. Many siblings reported a dislike for the common assumption that their affected sibling is a burden on the family. Most participants reported feeling some degree of responsibility for their affected sibling, but many also reported that they enjoy this role. Sixty-three parents from 36 families responded to the survey. Most parents felt their typically developing children enjoyed teaching new things to their affected child as well as being a good role model for them. Most parents also felt their typically developing child was comfortable telling others about their sibling's condition. Recommendations for interventions and future research are discussed.

Predictors of Changes in Height, Weight, and Body Mass Index After Initiation of Central Nervous System Stimulants in Children with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: To identify predictors of changes in height, weight, and body mass index (BMI) in children with attention deficit hyperactivity disorder (ADHD) starting central nervous system (CNS) stimulants. STUDY DESIGN: There were 230 medication-naïve children aged 5-12 years with ADHD who participated in a randomized trial evaluating the impact of CNS stimulants on growth over 30 months. This observational analysis focused on the 141 participants using study medication for 65 or more days in the first 6-months after starting medication. Biometric variables, ADHD, and oppositional defiant disorder symptom scores at medication initiation, and medication use over the study were examined as predictors of changes in standardized (z) height, weight, and BMI. RESULTS: Mean changes in z-BMI, z-weight. and z-height were negative throughout the study. The most consistent predictors of change in z-BMI, z-weight, and z-height were percent days medicated and total medication exposure. Children with lower z-height and z-weight at medication initiation experienced greater z-BMI and z-weight decreases over the first 6 months on medication. Greater appetite suppression during dose optimization predicted greater decreases in z-weight over the entire study and a greater decrease in z-height over the first 6 months on medication. z-weight change correlated with z-height change. Behavioral symptoms did not predict changes in z-BMI, z-weight, or z-height. CONCLUSIONS: How much and how often CNS stimulants are used predicts changes in z-BMI, z-weight, and z-height in children. Even smaller and lighter children may be at risk for decreases in z-weight and z-BMI. Parent ratings of appetite during dose titration may serve as feasible indicators of future weight and height change in children using CNS stimulants. TRIAL REGISTRATION: Clinicialtrials.gov: NCT01109849.

Impact of CNS Stimulants for Attention-Deficit/Hyperactivity Disorder on Growth: Epidemiology and Approaches to Management in Children and Adolescents.

Central nervous system stimulants are established treatments for pediatric attention-deficit/hyperactivity disorder with robust efficacy data. Reductions in appetite, weight, and growth velocity are some of the most common concerns regarding the long-term use of central nervous system stimulants in developing children. They are associated with suppression of weight and body mass index in childhood. However, both weight and body mass index often progressively increase over adolescence at rates faster than those seen in non-attention-deficit/hyperactivity disorder youth to the degree that attention-deficit/hyperactivity disorder is associated with elevated body mass index by the end of adolescence regardless of medication use. The capacity of central nervous system stimulants to slow growth was identified 50 years ago. Recent work has established that the growth deficits accumulate during the first 2 years of use and may persist provided medication is used. Early initiation coupled with persistent use through adolescence is most likely to be associated with clinical impactful growth suppression. There has been limited formal investigation of treatments for stimulant-associated reductions in weight and height. The most robust evidence exists for drug holidays improving weight gain. Observational studies suggest that limiting lifetime exposure or discontinuing medication is associated with greater adult height. Additional research is needed to identify the causal mechanisms driving the observed slowing in growth as well as the identification of predictors of clinically impactful growth suppression.

Prevalence and factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes: A report from a tertiary medical center in Central Pennsylvania.

Objective: To explore the rate and factors associated with diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in a single tertiary medical centre in Central Pennsylvania. Methods: Retrospective chart review of all individuals ≤ 18 years of age who were diagnosed with T1D (N = 350) at the Penn State Hershey Pediatric Diabetes Clinic from January 2017 to December 2019. We report logistic regression models for DKA at diagnosis of T1D for age, gender, race/ethnicity, BMI percentile, health insurance, outcome of any healthcare encounter 30 days prior to T1D diagnosis, HbA1c level, altered mental status at diagnosis, and diagnosis of autism spectrum disorder and a multivariable logistic regression model including all aforementioned variables. Results: Of the 350 newly diagnosed children with T1D from 2017 to 2019, 161/350 (46%) presented in DKA. Among patients with DKA, there were 45 (28%) in mild DKA and 116 (72%) in moderate/severe DKA, which represents 13% and 33% of all patients diagnosed with T1D, respectively. Variables associated with increased risk of DKA at presentation of T1D included age (<3 or 9-13), BMI percentile (<3% or > 97%), no referral during preceding healthcare encounter, HbA1c level and altered mental status. In a multivariable model, age (<3 or 9-13), no referral during preceding healthcare encounter, HbA1c level and altered mental status were associated with DKA at presentation, whereas gender, race/ethnicity, BMI percentile, health insurance and autism spectrum disorder diagnosis were not. Discussion: Our study notes an overall higher rate of DKA at diagnosis (46%) compared to the SEARCH study (approximately 30%) but a lower rate compared to a recent study in Colorado children (58%).

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Acanthosis nigricans as a composite marker of cardiometabolic risk and its complex association with obesity and insulin resistance in Mexican American children.

AIM: Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). METHODS: We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. RESULTS: Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI→HOMA-IR→AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. CONCLUSION: Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.

Challenges and Successes in Raising a Child With Type 1 Diabetes and Autism Spectrum Disorder: Mixed Methods Study.

BACKGROUND: Self-management of type 1 diabetes (T1D) requires numerous decisions and actions by people with T1D and their caregivers and poses many daily challenges. For those with T1D and a developmental disorder such as autism spectrum disorder (ASD), more complex challenges arise, though these remain largely unstudied. OBJECTIVE: This study aimed to better understand the barriers and facilitators of raising a child with T1D and ASD. Secondary analysis of web-based content (phase 1) and telephone interviews (phase 2) were conducted to further expand the existing knowledge on the challenges and successes faced by these families. METHODS: Phase 1 involved a qualitative analysis of publicly available online forums and blog posts by caregivers of children with both T1D and ASD. Themes from phase 1 were used to create an interview guide for further in-depth exploration via interviews. In phase 2, caregivers of children with both T1D and ASD were recruited from Penn State Health endocrinology clinics and through the web from social media posts to T1D-focused groups and sites. Interested respondents were directed to a secure web-based eligibility assessment. Information related to T1D and ASD diagnosis, contact information, and demographics were collected. On the basis of survey responses, participants were selected for a follow-up telephone interview and were asked to complete the adaptive behavior assessment system, third edition parent form to assess autism severity and upload a copy of their child's most recent hemoglobin A1c (HbA1c) result. Interviews were transcribed, imported into NVivo qualitative data management software, and analyzed to determine common themes related to barriers and facilitators of raising a child with both ASD and T1D. RESULTS: For phase 1, 398 forum posts and blog posts between 2009 and 2016 were analyzed. Common themes related to a lack of understanding by the separate ASD and T1D caregiver communities, advice on coping techniques, rules and routines, and descriptions of the health care experience. For phase 2, 12 eligible respondents were interviewed. For interviewees, the average age of the child at diagnosis with T1D and ASD was 7.92 years and 5.55 years, respectively. Average self-reported and documented HbA1c levels for children with T1D and ASD were 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol), respectively. Common themes from the interviews related to increased emotional burden, frustration surrounding the amount of information they are expected to learn, and challenges in the school setting. CONCLUSIONS: Caregivers of children with both T1D and ASD face unique challenges, distinct from those faced by caregivers of individuals who have either disorder alone. Understanding these challenges may help health care providers in caring for this unique population. Referral to the diabetes online community may be a potential resource to supplement the care received by the medical community.

Association of quality of paediatric epilepsy care with mortality and unplanned hospital admissions among children and young people with epilepsy in England: a national longitudinal data linkage study.

BACKGROUND: Concerns have been raised about variation in care quality and outcomes among children and young people with epilepsies in England. We aimed to investigate the association between quality of paediatric care, hospital admissions, and all-cause deaths among epilepsy patients. METHODS: In this longitudinal data linkage study of paediatric epilepsy services in England, we linked unit-level data from round 1 (2009-11) and round 2 (2013-14) of the Epilepsy12 national clinical audit, with death registrations from the UK Office for National Statistics and data for unplanned hospital admissions from Hospital Episode Statistics. We investigated the association between unit-level performance in involving a paediatrician with epilepsy expertise, an epilepsy specialist nurse, and a paediatric neurologist (where appropriate) in round 1 and the proportion of adolescents (aged 10-18 years) with epilepsy admitted to each unit who subsequently died during the study period (April 1, 2009, to March 31, 2015). We also investigated whether change in Epilepsy12 performance between the two audit rounds was associated with changes in the standardised ratio of observed-to-expected unplanned epilepsy admissions over the same period. FINDINGS: In 99 units with data for the analyses relating to paediatricians with epilepsy expertise and epilepsy specialist nurses, 134 (7%) of 1795 patients died during the study period, 88 (5%) of whom died after the transition to adult service. In 55 units with data for the analyses relating to paediatric neurologists, 79 (7%) of 1164 patients died, 54 (5%) of whom did so after the transition. In regression models adjusting for population, unit, and hospital activity characteristics, absolute reductions in total mortality risk (6·4 percentage points, 95% CI 0·1-12·7) and mortality risk after transition (5·7 percentage points, 0·6-10·8) were found when comparing units where all versus no eligible patients were seen by a paediatric neurologist. Units where all eligible patients were seen by a paediatric neurologist were estimated to have absolute reductions of 4·6 percentage points (0·3-8·9) in total mortality and of 4·6 percentage points (1·2-8·0) in post-transition mortality, compared with units where no or some eligible patients were seen by a paediatric neurologist. There was no significant association between performance on being seen by an epilepsy specialist nurse or by a paediatrician with epilepsy expertise and mortality. In units where access to an epilepsy specialist nurse decreased, the standardised ratio of epilepsy admissions increased by a mean of 0·21 (0·01-0·42). INTERPRETATION: Among adolescents with epilepsy, greater involvement of tertiary specialists in paediatric care is associated with decreased all-cause mortality in the period after transition to adult services. Reduced access to an epilepsy specialist nurse was associated with an increase in paediatric epilepsy admissions. FUNDING: The Health Foundation.

The Impact of Age of Transfer on Outcomes in the Transition From Pediatric to Adult Health Systems: A Systematic Review of Reviews.

PURPOSE: International guidance on health-care transition has existed for over a decade; however, many unanswered questions remain. This systematic review of reviews aimed to answer the question: is a later age of transfer from pediatric to adult health care associated with improved health and health service outcomes? METHODS: We included systematic reviews which considered at least one long-term condition and provided outcome data from adult services. Methodology of primary studies was not an exclusion criterion. We searched multiple databases and conducted an initial search in May 2015 which was repeated in May 2017. All reviews were assessed for quality using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) tool. Reviews that scored less than 22 were excluded. RESULTS: Initial searches identified 6,149 papers. Forty-three reviews met exclusion and inclusion criteria, and 15 reviews also met quality criteria. With one exception, primary studies from reviews which only considered quantitative evidence found that a delayed age of transfer resulted in improved outcomes. Qualitative and mixed-methods evidence supported the view that age 18 was an appropriate time of transfer. CONCLUSION: We found moderate evidence that models of transition which transfer young people in late adolescence or early adulthood can improve transition outcomes and patient satisfaction.

Effects of temperament at feedlot arrival and breed type on growth efficiency, feeding behavior, and carcass value in finishing heifers.

Objectives were to evaluate the effects of temperament at feedlot arrival and breed type on productivity, feed efficiency, feeding behavior, and carcass quality traits in finishing beef heifers, and to examine interactions between temperament and breed type. Heifers (Angus, Braford, Brangus, and Simbrah, N = 411, BW = 280 kg) were fed a high-grain diet (ME = 3.0 Mcal/kg DM) in pens equipped with electronic feed bunks. Quality grade (QG), yield grade (YG), and Warner-Bratzler shear (WBS) force values (day 1 and 14 postmortem) were evaluated. Relative exit velocity (REV) at feedlot arrival was used as a covariate in mixed models to assess the effects of temperament and interactions with breed type, with means compared at ±1 SD from the mean initial REV. Calm heifers (mean REV minus 1 SD) had 4% greater (P < 0.001) initial BW, 12% greater (P < 0.001) ADG, 8% greater (P < 0.001) DMI, and 4% greater (P < 0.02) G:F than heifers with excitable temperaments (mean REV plus 1 SD). A temperament × breed interaction was detected (P < 0.01) for residual feed intake (RFI). Braford heifers had a more (P < 0.05) negative REV covariate slope (-1.49 ± 0.65) than the other breeds, such that excitable Braford heifers had lower (P < 0.05) RFI than the other breeds with excitable temperaments. Temperament × breed interactions were observed (P < 0.001) for DMI per BW0.75 and bunk visit (BV) duration. Braford heifers had more (P < 0.05) negative REV covariate slopes for both traits than Angus, Brangus, and Simbrah heifers such that excitable Braford heifers consumed less (P < 0.05) DMI per BW0.75 and had less BV duration compared to excitable Angus and Brangus heifers. Calm heifers had 9% greater (P < 0.01) meal duration, and consumed meals that were 22% longer (P < 0.001) and 17% larger (P < 0.001) compared to excitable heifers. Calm heifers had 12% more (P < 0.001) BV events per meal then excitable heifers. Carcasses from calm heifers were 4% heavier (P < 0.05) and had 7% greater (P = 0.05) backfat (BF) depth and tended to have 4% greater (P = 0.07) USDA YG than carcasses from excitable heifers. Additionally, loin steaks from calm heifers had 8% lower (P < 0.05) WBS force than steaks from excitable heifers. Based on a carcass grid with discounts and premiums for HCW, QG, YG, and tenderness, calm heifers returned $62 more (P < 0.01) revenue per animal than excitable heifers. These results demonstrate that heifers with divergent phenotypes for temperament on feedlot arrival differ in their performance, feed efficiency, and feeding behavior patterns, as well as carcass quality and revenue.

Abnormal bone mineral content and density in people with tetrasomy 18p.

Tetrasomy 18p is a rare chromosomal abnormality, resulting from an additional iso-chromosome composed of two copies of the short arm. It is characterized by craniofacial abnormalities, neuromuscular dysfunction, and developmental delay. The Chromosome 18 Clinical Research Center has established the largest cohort of individuals with this rare genetic condition. Here, we describe a case series of 21 individuals with tetrasomy 18p who have a previously unreported clinical finding: low bone mineral density. Most individuals met criteria for low bone density despite being relatively young (mean age of 21 years). Clinicians providing care to individuals affected by Tetrasomy 18p should be aware of their increased risk for decreased bone density and pathological fractures.

Chromosome 18 gene dosage map 2.0.

In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chromosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.

Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: Relationships to glycemic control and other risk factors.

AIMS: We aimed to determine the prevalence of arterial stiffness in young adults with youth-onset type 2 diabetes who previously participated in the TODAY clinical trial and whether arterial stiffness is influenced by their prior diabetes treatment assignment or glycemic control. METHODS: We measured arterial stiffness by femoral, radial, and foot pulse wave velocity (PWV), augmentation index (AIx), and brachial distensibility (BrachD) in 453 TODAY participants (age 20.8 ±â€¯2.5 years, diabetes duration 7.6 ±â€¯1.5 years, 36.4% male, BMI 36.7 ±â€¯8.2 kg/m2) at a mean of 7.6 years post-randomization. Increased arterial stiffness in TODAY youth was defined compared with data from lean controls. We assessed whether glycemic control over time or diabetes treatment in TODAY was associated with arterial stiffness. RESULTS: Arterial stiffness was identified in up to 50% of TODAY participants. Prior diabetes treatment assignment was not associated with higher arterial stiffness. Glycemic control over time was associated with PWV radial and foot only. Age, race-ethnicity, sex, higher blood pressure and BMI were also associated with higher arterial stiffness. CONCLUSIONS: Nearly half of TODAY youth have increased arterial stiffness. Targeting blood pressure and perhaps obesity and glycemic control may positively impact arterial health in adolescents with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.govNCT00081328.

Effectiveness of Universal Self-regulation-Based Interventions in Children and Adolescents: A Systematic Review and Meta-analysis.

Importance: Childhood and adolescence self-regulation (SR) is gaining importance as a target of intervention because of mounting evidence of its positive associations with health, social and educational outcomes. Objective: To conduct a systematic review and meta-analysis of rigorously evaluated interventions to improve self-regulation in children and adolescents. Data Sources: Keyword searches of the PsycINFO, PubMed, EMBASE, CINAHL Plus, ERIC, British Education Index, Child Development and Adolescent Studies, and CENTRAL were used to identify all studies published through July 2016. Study Selection: To be eligible for this review, studies had to report cluster randomized trials or randomized clinical trials, evaluate universal interventions designed to improve self-regulation in children and adolescents aged 0 to 19 years, include outcomes associated with self-regulation skills, and be published in a peer-reviewed journal with the full text available in English. Data Extraction and Synthesis: A total of 14 369 published records were screened, of which 147 were identified for full-text review and 49 studies reporting 50 interventions were included in the final review. Results were summarized by narrative review and meta-analysis. Main Outcomes and Measures: Self-regulation outcomes in children and adolescents. Results: This review identified 17 cluster randomized trials and 32 randomized clinical trials evaluating self-regulation interventions, which included a total of 23 098 participants ranging in age from 2 to 17 years (median age, 6.0 years). Consistent improvement in self-regulation was reported in 16 of 21 curriculum-based interventions (76%), 4 of the 8 mindfulness and yoga interventions (50%), 5 of 9 family-based programs (56%), 4 of 6 exercise-based programs (67%), and 4 of 6 social and personal skills interventions (67%), or a total of 33 of 50 interventions (66%). A meta-analysis evaluating associations of interventions with self-regulation task performance scores showed a positive effect of such interventions with pooled effect size of 0.42 (95% CI, 0.32-0.53). Only 24 studies reported data on distal outcomes (29 outcomes). Positive associations were reported in 11 of 13 studies (85%) on academic achievement, 4 of 5 studies on substance abuse (80%), and in all studies reporting on conduct disorders (n = 3), studies on social skills (n = 2), studies on depression (n = 2), studies on behavioral problems (n = 2), and study on school suspensions (n = 1). No effect was seen on 2 studies reporting on academic achievement, 1 study reporting on substance abuse, and 1 additional study reporting on psychological well-being. Conclusions and Relevance: A wide range of interventions were successful in improving self-regulation in children and adolescents. There was improvement in distal academic, health, and behavioral outcomes in most intervention groups compared with controls.

The Chromosome 18 Clinical Resource Center.

BACKGROUND: The Chromosome 18 Clinical Research Center has created a pediatrician-friendly virtual resource center for managing patients with chromosome 18 abnormalities. To date, children with rare chromosome abnormalities have been cared for either symptomatically or palliatively as a reaction to the presenting medical problems. As we enter an era of genomic-informed medicine, we can provide children, even those with individually unique chromosome abnormalities, with proactive medical care and management based on the most contemporary data on their specific genomic change. It is problematic for practicing physicians to obtain and use the emerging data on specific genes because this information is derived from diverse sources (e.g., animal studies, case reports, in vitro explorations) and is often published in sources that are not easily accessible in the clinical setting. METHODS: The Chromosome 18 Clinical Resource Center remedies this challenging problem by curating and synthesizing the data with clinical implications. The data are collected from our database of over 26 years of natural history and medical data from over 650 individuals with chromosome 18 abnormalities. RESULTS: The resulting management guides and video presentations are a first edition of this collated data specifically oriented to guide clinicians toward the optimization of care for each child. CONCLUSION: The chromosome 18 data and guides also serve as models for an approach to the management of any individual with a rare chromosome abnormality of which there are over 1,300 born every year in the US alone.

How adolescent health influences education and employment: investigating longitudinal associations and mechanisms.

BACKGROUND: Education is recognised as a strong determinant of health. Yet there is increasing concern that health in adolescence may also influence educational attainments and future life chances. We examined associations between health in early adolescence and subsequent academic and employment outcomes, exploring potential mediators of these relationships to inform intervention strategies. METHODS: We used data from the Longitudinal Study of Young People in England. Adolescent health was measured at waves 1 and 2. Outcomes included educational attainment at age 16 years and being NEET (not in education, employment or training) at age 19 years. Associations were adjusted for ethnicity, area-level deprivation and early adolescent academic attainment. Where significant associations were identified, we examined the role of hypothesised mediators including attendance and truancy, classroom behaviour, substance use and psychological distress. RESULTS: Health conditions in early adolescence predicted poor subsequent education and employment outcomes (ORs ranged from 1.25 to 1.72) with the exception of long-term chronic conditions and NEET status, which were unassociated. The most consistent mediating variable was social exclusion. School behaviour, truancy and substance use were significant mediators for mental health. Long-term absences mediated associations between mental health and physical health and later outcomes. CONCLUSIONS: Health is a key component of academic and vocational achievement. Investment in health is a way of improving life chances. The identification of key mediators such as social exclusion and truancy indicate areas where screening for health conditions and provision of targeted support could improve educational, employment and health outcomes.

Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents.

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment-insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood-based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA-IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA-IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.

National Beef Quality Audit-2016: assessment of cattle hide characteristics, offal condemnations, and carcass traits to determine the quality status of the market cow and bull beef industry.

To continue the series that began in 1994, the National Beef Quality Audit (NBQA) - 2016 was conducted to quantify the quality status of the market cow and bull beef sector, as well as determine improvements made in the beef and dairy industry since 2007. The NBQA-2016 was conducted from March through December of 2016, and assessed hide-on carcasses (n = 5,278), chilled carcasses (n = 4,285), heads (n = 5,720), and offal items (n = 4,800) in 18 commercial processing facilities throughout the United States. Beef cattle were predominantly black-hided; 68.0% of beef cows and 67.2% of beef bulls possessed a black hide. Holstein was the predominant type of dairy animal observed. Just over half (56.0%) of the cattle surveyed had no mud contamination on the hide, and when mud was present, 34.1% of cattle only had small amounts. Harvest floor assessments found 44.6% of livers, 23.1% of lungs, 22.3% of hearts, 20.0% of viscera, 8.2% of heads, and 5.9% of tongues were condemned. Liver condemnations were most frequently due to abscess presence. In contrast, contamination was the primary reason for condemnation of all other offal items. Of the cow carcasses surveyed, 17.4% carried a fetus at the time of harvest. As expected, mean carcass weight and loin muscle area values observed for bulls were heavier and larger than cows. The marbling scores represented by cull animal carcasses were most frequently slight and traces amounts. Cow carcasses manifested a greater amount of marbling on average than bull carcasses. The predominant fat color score showed all carcasses surveyed had some level of yellow fat. Only 1.3% of carcasses exhibited signs of arthritic joints. Results of the NBQA-2016 indicate there are areas in which the beef and dairy industries have improved and areas that still need attention to prevent value loss in market cows and bulls.

Conduct problems trajectories and psychosocial outcomes: a systematic review and meta-analysis.

There is increasing evidence that youth who follow the early onset persistent (EOP), adolescent-onset (AO) and childhood-limited (CL) trajectories of conduct problems show varying patterns of health, mental health, educational, and social outcomes in adulthood. However, there has been no systematic review and meta-analysis on outcomes associated with different conduct problems trajectories. We systematically reviewed the literature of longitudinal studies considering outcomes of three conduct problems trajectories: EOP, AO, and CL compared with individuals with low levels of conduct problems (low). We performed a series of meta-analyses comparing each trajectory to the low group for eight different outcomes in early adulthood or later. Thirteen studies met our inclusion criteria. Outcomes were mental health (depression), cannabis use, alcohol use, self-reported aggression, official records of antisocial behaviour, poor general health, poor education, and poor employment. Overall, EOP individuals showed significant higher risk of poor outcome followed by AO individuals, CL individuals, and finally participants in the low group. All conduct problems trajectories showed higher risk of poor psychosocial outcomes compared to the low group, but the magnitude of risk differed across trajectories, with a general trend for the EOP to perform significantly worse, followed by the AO and CL. Early intervention is recommended across domains to maximise likelihood of desistance from antisocial behaviour and improvement on several psychosocial outcomes.