Health-related quality of life of Canadian children and youth prenatally exposed to alcohol

BACKGROUND: In Canada, the incidence of Fetal Alcohol Spectrum Disorder (FASD) has been estimated to be 1 in 100 live births. Caused by prenatal exposure to alcohol, FASD is the leading cause of neuro-developmental disabilities among Canadian children, and youth. Objective: To measure the health-related quality of life (HRQL) of Canadian children and youth diagnosed with FASD. METHODS: A prospective cross-sectional study design was used. One-hundred and twenty-six (126) children and youth diagnosed with FASD, aged 8 to 21 years, living in urban and rural communities throughout Canada participated in the study. Participants completed the Health Utilities Index Mark 3 (HUI3). HUI3 measures eight health attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. Utilities were used to measure a single cardinal value between 0 and 1.0 (0 = all-worst health state; 1 = perfect health) to reflect the global HRQL for that child. Mean HRQL scores and range of scores of children and youth with FASD were calculated. A one-sample t-test was used to compare mean HRQL scores of children and youth with FASD to those from the Canadian population. RESULTS: Mean HRQL score of children and youth with FASD was 0.47 (95% CI: 0.42 to 0.52) as compared to a mean score of 0.93 (95% CI: 0.92 to 0.94) in those from the general Canadian population (p < 0.001). Children demonstrated moderate to severe dysfunction on the single-attributes of cognition and emotion. CONCLUSION: Children and youth with FASD have significantly lower HRQL than children and youth from the general Canadian population. This finding has significant implications for practice, policy development, and research

Healthcare professionals' perceptions of pain in infants at risk for neurological impairment

BACKGROUND: To determine whether healthcare professionals perceive the pain of infants differently due to their understanding of that infant's level of risk for neurological impairment. METHOD: Neonatal Intensive Care Units (NICU's) at two tertiary pediatric centers. Ninety-five healthcare professionals who practice in the NICU (50 nurses, 19 physicians, 17 respiratory therapists, 9 other) participated. They rated the pain (0–10 scale and 0–6 Faces Pain Scale), distress (0–10), effectiveness of cuddling to relieve pain (0–10) and time to calm without intervention (seconds) for nine video clips of neonates receiving a heel stick. Prior to each rating, they were provided with descriptions that suggested the infant had mild, moderate or severe risk for neurological impairment. Ratings were examined as a function of the level of risk described. RESULTS: Professionals' ratings of pain, distress, and time to calm did not vary significantly with level of risk, but ratings of the effectiveness of cuddling were significantly lower as risk increased [F (2,93) = 4.4, p = .02]. No differences in ratings were found due to participants' age, gender or site of study. Physicians' ratings were significantly lower than nurses' across ratings. CONCLUSION: Professionals provided with visual information regarding an infants' pain during a procedure did not display the belief that infants' level of risk for neurological impairment affected their pain experience. Professionals' estimates of the effectiveness of a nonpharmacological intervention did differ due to level of risk

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department

<p>Abstract</p> <p>Background</p> <p>Although sucrose has been accepted as an effective analgesic agent for procedural pain in neonates, previous studies are largely in the NICU population using the procedure of heel lance. This is the first report of the effect of sucrose, pacifier or the combination thereof for the procedural pain of venipuncture in infants in the pediatric emergency department population.</p> <p>Methods</p> <p>The study design was a double (sucrose) and single blind (pacifier), placebo-controlled randomized trial – factorial design carried out in a pediatric emergency department. The study population was infants, aged 0 – 6 months. Eighty-four patients were randomly assigned to one of four groups: a) sucrose b) sucrose & pacifier c) control d) control & pacifier. Each child received 2 ml of either 44% sucrose or sterile water, by mouth. The primary outcome measure: FLACC pain scale score change from baseline. Secondary outcome measures: crying time and heart rate change from baseline.</p> <p>Results</p> <p>Sucrose did not significantly reduce the FLACC score, crying time or heart rate. However sub-group analysis revealed that sucrose had a much greater effect in the younger groups. Pacifier use reduced FLACC score (not statistically significant), crying times (statistically significant) but not heart rate. Subgroup analysis revealed a mean crying time difference of 76.52 seconds (p < 0.0171) (0–1 month) and 123.9 seconds (p < 0.0029) (1–3 month). For subgroup age > 3 months pacifier did not have any significant effect on crying time. Age adjusted regression analysis revealed that both sucrose and pacifier had significant effects on crying time. Crying time increased with both increasing age and increasing gestational age.</p> <p>Conclusion</p> <p>Pacifiers are inexpensive, effective analgesics and are easy to use in the PED for venipuncture in infants aged 0–3 months. The benefits of sucrose alone as an analgesic require further investigation in the older infant, but sucrose does appear to provide additional benefit when used with a pacifier in this age group.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN15819627</p

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association

Rationale: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. Objective: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. Methods: Associations of n-3 PUFA biomarkers (a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N=16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNPassociations and their interactions with n-3PUFAs. Results: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P-2df = 9.4 x 10(-9) across discovery and replication cohorts). The rs11693320-A allele (frequency, similar to 80%) was associated with lower FVC (P-SNP = 2.1 x 10(-9); beta(SNP) = 2161.0 ml), and the association was attenuated by higher DHA levels (P-SNPxDHA interaction = 2.1x10(-7); beta(SNPxDHA interaction) = 36.2 ml). Conclusions: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction

Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease