Immunity and field efficacy of type 2-containing polio vaccines after cessation of trivalent oral polio vaccine: A population-based serological study in Pakistan

Background: In Pakistan and other countries using oral polio vaccine (OPV), immunity to type 2 poliovirus is now maintained by a single dose of inactivated polio vaccine (IPV) in routine immunization, supplemented in outbreak settings by monovalent OPV type 2 (mOPV2) and IPV. While well-studied in clinical trials, population protection against poliovirus type 2 achieved in routine and outbreak settings is generally unknown.Methods: We conducted two phases of a population-based serological survey of 7940 children aged 6-11 months old, between November 2016 and October 2017 from 13 polio high-risk locations in Pakistan.Results: Type 2 seroprevalence was 50% among children born after trivalent OPV (tOPV) withdrawal (April 2016), with heterogeneity across survey areas. Supplementary immunization activities (SIAs) with mOPV2 followed by IPV improved population immunity, varying from 89% in Pishin to 64% in Killa Abdullah, with little observed marginal benefit of subsequent campaigns. In the other high-risk districts surveyed, a single SIA with IPV was conducted and appeared to improve immunity to 57% in Karachi to 84% in Khyber.Conclusions: Our study documents declining population immunity following trivalent OPV withdrawal in Pakistan, and wide heterogeneity in the population impact of supplementary immunization campaigns. Differences between areas, attributable to vaccination campaign coverage, were far more important for type 2 humoral immunity than the number of vaccination campaigns or vaccines used. This emphasizes the importance of immunization campaign coverage for type 2 outbreak response in the final stages of polio eradication. Given the declining type 2 immunity in new birth cohorts it is also recommended that 2 or more doses of IPV should be introduced in the routine immunization program of Pakistan

Behavior of QQ-Plots and Genomic Control in Studies of Gene-Environment Interaction

Genome-wide association studies of gene-environment interaction (GxE GWAS) are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots) and Genomic Control are being used to assess and correct for population substructure. However, in GE work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in GE GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in GE GWAS can alleviate this problem

Development curves of communication and social interaction in individuals with cerebral palsy

Aim: To determine development curves of communication and social interaction from childhood into adulthood for individuals with cerebral palsy (CP). Method: This Pediatric Rehabilitation Research in the Netherlands (PERRIN)-DECADE study longitudinally assessed 421 individuals with CP, aged from 1 to 20 years at baseline, after 13 years (n=121 at follow-up). Communication and social interactions were assessed using the Vineland Adaptive Behavior Scales. We estimated the average maximum performance limit (level) and age at which 90% of the limit was reached (age90) using nonlinear mixed-effects modeling. Results: One-hundred individuals without intellectual disability were aged 21 to 34 years at follow-up (39 females, 61 males) (mean age [SD] 28y 5mo [3y 11mo]). Limits of individuals without intellectual disability, regardless of Gross Motor Function Classification System (GMFCS) level, approached the maximum score and were significantly higher than those of individuals with intellectual disability. Ages90 ranged between 3 and 4 years for receptive communication, 6 and 7 years for expressive communication and interrelationships, 12 and 16 years for written communication, 13 and 16 years for play and leisure, and 14 and 16 years for coping. Twenty-one individuals with intellectual disability were between 21 and 27 years at follow-up (8 females, 13 males) (mean age [SD] 24y 7mo [1y 8mo]). Individuals with intellectual disability in GMFCS level V showed the least favourable development, but variation between individuals with intellectual disability was large. Interpretation: Individuals with CP and without intellectual disability show developmental curves of communication and social interactions similar to typically developing individuals, regardless of their level of motor function. Those with intellectual disability reach lower performance levels and vary largely in individual development. What this paper adds: Communication and social interactions in individuals with cerebral palsy without intellectual disability develop similarly to typically developing individuals. Communication and social interactions of individuals with intellectual disability develop less favourably and show large variation

Childhood factors predict participation of young adults with cerebral palsy in domestic life and interpersonal relationships: a prospective cohort study

Purpose: To determine childhood predictors of participation in domestic life and interpersonal relationships of young adults with cerebral palsy (CP). Materials and methods: This 13-year follow-up of an existing cohort (baseline age 9–13 years) included 67 young adults with CP (age 21–27 years). The Vineland adaptive behavior scales (VABS) and Life Habits questionnaire were used to assess attendance and difficulty in participation in domestic life and interpersonal relationships. Baseline factors were categorised according to the international classification of functioning, disability, and health. Stepwise multiple linear regression analyses determined significant predictors (p < 0.05). Results: Lower manual ability, intellectual disability (ID), epilepsy and lower motor capacity predicted decreased future participation in domestic life, and/or interpersonal relationships (explained variance R2 ¼ 67–87%), whereas no association was found with environmental and personal factors. Extending models with baseline fine motor skills, communication, and interpersonal relationships increased R2 to 79–90%. Conclusions: Childhood factors account for 79–90% of the variation in young adult participation in domestic life and interpersonal relationships of individuals with CP. Children with limited motor capacity, low manual ability, ID, or epilepsy are at risk for restrictions in participation in young adulthood. Addressing fine motor, communication, and social skills in paediatric rehabilitation might promote young adult participation

Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation

BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986–2004), longitudinal data on PM<10 μm in diameter (PM10), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately 2.5×106 SNP×PM10 interactions among nine Women’s Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (n=22,158), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis. RESULTS: A common variant (rs1619661; coded allele: T) significantly modified the QT-PM10 association (p=2.11×10−8). At PM10 concentrations >90th percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower PM10 concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from CXCL12, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type Ca2+ channel. CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to PM10-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency’s National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP34

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

An evaluation of the effectiveness of PROMPT therapy in improving speech production accuracy in six children with cerebral palsy

This study evaluates perceptual changes in speech production accuracy in six children (3 – 11 years) with moderate-to-severe speech impairment associated with cerebral palsy before, during, and after participation in a motor-speech intervention program (Prompts for Restructuring Oral Muscular Phonetic Targets). An A1BCA2 single subject research design was implemented. Subsequent to the baseline phase (phase A1), phase B targeted each participant’s first intervention priority on the PROMPT motor-speech hierarchy. Phase C then targeted one level higher. Weekly speech probes were administered, containing trained and untrained words at the two levels of intervention, plus an additional level that served as a control goal. The speech probes were analysed for motor-speech-movement-parameters and perceptual accuracy. Analysis of the speech probe data showed all participants recorded a statistically significant change. Between phases A1 – B and B – C 6/6 and 4/6participants, respectively, recorded a statistically significant increase in performance level on the motor speech movement patterns targeted during the training of that intervention. The preliminary data presented in this study make a contribution to providing evidence that supports the use of a treatment approach aligned with dynamic systems theory to improve the motor-speech movement patterns and speech production accuracy in children with cerebral palsy

A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 × 10-8, including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 × 10 -21); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 × 10 -12); 5p13.1 near PTGER4 (rs7720838, P = 8.2 × 10 -11); 2q33.1 in PLCL1 (rs10497813, P = 6.1 × 10-10), 3q28 in LPP (rs9860547, P = 1.2 × 10-9); 20q13.2 in NFATC2 (rs6021270, P = 6.9 × 10-9), 4q27 in ADAD1 (rs17388568, P = 3.9 × 10-8); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 × 10-8). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 × 10-12), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease

Factors associated with the participation of children with complex communication needs

The aim of this study was to conduct a preliminary analysis of relations between child and environmental variables, including factors related to communication aid provision, and participation in informal everyday activities in a sample of children with complex communication needs.Ninety-seven caregivers of children provided with communication aids responded to a questionnaire survey. Child variables assessed were level of ability, trait emotional self-efficacy, and competence in communication aid use. Environmental variables assessed were the impact of childhood disability on the family, family socio-economic category, perceived reliability of electronic communication aids provided to children, and ease of use of the aid. The outcome measure was the intensity of child participation in informal activities.Significant correlations were observed between participation scores and the following variables: child age, level of ability, trait emotional self-efficacy, and family impact of childhood disability. Regression analyses highlighted trait emotional self-efficacy and, to a lesser degree, family impact of childhood disability as the strongest potential predictors of participation.While aspects of child personality may be difficult to disentangle from behaviours related to disability type or developmental age, this research highlights a clinical requirement to assess systematically child behaviours relating to their general emotional functioning. (C) 2010 Elsevier Ltd. All rights reserved