Physiological and Psychological Effects of Deception on Pacing Strategy and Performance: A Review

The aim of an optimal pacing strategy during exercise is to enhance performance whilst ensuring physiological limits are not surpassed, which has been shown to result in a metabolic reserve at the end of the exercise. There has been debate surrounding the theoretical models that have been proposed to explain how pace is regulated, with more recent research investigating a central control of exercise regulation. Deception has recently emerged as a common, practical approach to manipulate key variables during exercise. There are a number of ways in which deception interventions have been designed, each intending to gain particular insights into pacing behaviour and performance. Deception methodologies can be conceptualised according to a number of dimensions such as deception timing (prior to or during exercise), presentation frequency (blind, discontinuous or continuous) and type of deception (performance, biofeedback or environmental feedback). However, research evidence on the effects of deception has been perplexing and the use of complex designs and varied methodologies makes it difficult to draw any definitive conclusions about how pacing strategy and performance are affected by deception. This review examines existing research in the area of deception and pacing strategies, and provides a critical appraisal of the different methodological approaches used to date. It is hoped that this analysis will inform the direction and methodology of future investigations in this area by addressing the mechanisms through which deception impacts upon performance and by elucidating the potential application of deception techniques in training and competitive settings

Intrapartum antibiotics and childhood atopic dermatitis

Introduction: Atopic dermatitis (AD) in children significantly impacts families because of medical costs, lost hours, and secondary characteristics such as asthma and ancillary infections. We investigate whether children delivered vaginally to women receiving intrapartum antibiotics have a greater risk of AD when younger than the age of 2 years than their counterparts. Methods: We conducted a retrospective analysis of women who delivered child(ren) vaginally between 1996 and 2008. Women were identified as those who received intrapartum antibiotics and those who did not. Pediatric records were used to determine the incidence of AD. Results: We collected data for 492 mother- child pairs. Intrapartum antibiotics were administered during 128 births; 28.9% of those children were diagnosed with AD by age 2 years (relative risk [RR], 1.03; 95% confidence interval [CI], 0.75-1.41). Factors with the greatest risk of diagnosis of AD by 2 years of age were intrapartum antibiotic exposure for \u3e24 hours (RR, 1.99; 95% CI, 1.13-3.49), first born (RR, 1.78; 95% CI, 1.33-2.38), and higher maternal education (RR, 1.43; 95% CI, 0.99 -2.06). No statistical differences in the prevalence of AD related to parental eczema, maternal group B Streptococcus status, or gestational age existed. Conclusions: Exposure to antibiotics for \u3c24 hours during a vaginal delivery does not increase the risk of AD. Studies are needed to understand whether exposure for \u3e24 hours during the intrapartum period increases the risk of AD

Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics

It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 top-ranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discretized variables (depression, anxiety, age, sex, and race), we performed BN analysis in 529 CAMP subjects. We identified two nodes (depression and rs4672619 mapping to ERBB4 (Erb-B2 receptor tyrosine kinase 4)) that were within the Markov neighborhood of the symptom node in the network and then evaluated the interactive effects of depressive status and rs4672619 genotypes on asthma symptom severity. In childhood asthmatics with homozygous reference alleles, severe depression was related to less severe symptoms. However, in childhood asthmatics with heterozygous alleles and homozygous variant alleles, depression and symptom severity showed a positive correlation (interaction permutation P value =0.019). We then tried to evaluate whether the interactive effects that we found were sustained in another independent cohort of elderly asthmatics. Contrary to the findings from childhood asthmatics, elderly asthmatics with homozygous reference alleles showed a positive correlation between depression and symptom severity, and elderly asthmatics with heterozygous alleles and homozygous variant alleles showed a negative correlation (interaction permutation P value =0.003). In conclusion, we have identified a novel SNP, rs4672619, that shows interactive effects with depression on asthma symptom severity in childhood and elderly asthmatics in opposite directions.National Institutes of Health, US [R01 NR013391, R01 HL127332, U01 HL065899]; Ministry of Health and Welfare, Republic of Korea [2008-E33028-00, 2009-E33022-00, 2011-E33005-00]; Parker B. Francis FoundationOpen access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Genome-Wide Association Study of Short-Acting β2-Agonists. A Novel Genome-Wide Significant Locus on Chromosome 2 near ASB3

Rationaleβ2-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable.ObjectivesTo investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma.MethodsWe performed a GWAS of acute bronchodilator response (BDR) to inhaled β2-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals.Measurements and main resultsThe combined P value for four SNPs reached statistical genome-wide significance aftercorrecting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2.21 × 10(-10), 5.75 × 10(-8), 9.3 × 10(-8), and 3.95 × 10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 near the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population.ConclusionsThese GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma

Genome-wide association study of the age of onset of childhood asthma

BACKGROUND: Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children. OBJECTIVE: To identify genetic variants associated with earlier onset of childhood asthma. METHODS: We conducted the first genome-wide association study (GWAS) of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP), and used three independent cohorts from North America, Costa Rica, and Sweden for replication. RESULTS: Two SNPs were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: : rs9815663 (Fisher’s P value=2.31 × 10−8) and rs7927044 (P=6.54 × 10−9). Of these two SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10−7 < P < 8.22 ×10−6). Having ≥1 risk allele of the two SNPs of interest (rs9815663 and rs7927044) was associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP. CONCLUSIONS: We have identified two SNPs associated with earlier onset of childhood asthma in four independent cohorts

Genome-Wide Association Study of Short-Acting β 2

Rationale: β(2)-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable. Objectives: To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma. Methods: We performed a GWAS of acute bronchodilator response (BDR) to inhaled β(2)-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals. Measurements and Main Results: The combined P value for four SNPs reached statistical genome-wide significance aftercorrecting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2.21 × 10(−10), 5.75 × 10(−8), 9.3 × 10(−8), and 3.95 × 10(−8), respectively. The significant variants all map to a novel genetic region on chromosome 2 near the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population. Conclusions: These GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma

Genome-Wide Association Study of Short-Acting beta(2)-Agonists A Novel Genome-Wide Significant Locus on Chromosome 2 near ASB3

Rationale: [beta(2)-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable. Objectives: To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma. Methods: We performed a GWAS of acute bronchodilator response (BDR) to inhaled beta(2)-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top 50 SNPs were carried forward to replication in a population of 444 individuals. Measurements and Main Results: The combined P value for four SNPs reached statistical genome-wide significance after correcting for multiple comparisons. Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2:21 X 10(-10), 5.75 X 10(-8), 9.3 X 10(-8), 3.95 X 10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 neat the ASB3 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population. Conclusions: These GWAS findings for BDR in subjects with asthma suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in asthma

Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate

BackgroundLoss of bronchoprotection (LOBP) with a regularly used long-acting β2-adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to β2-adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate.ObjectiveWe sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients.MethodsWe conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250&nbsp;μg of fluticasone twice daily for 2&nbsp;weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8&nbsp;weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8&nbsp;weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC20 value.ResultsThe mean doubling dose reduction in SPMCh PC20 value was 0.50 and 0.27 with alendronate and placebo, respectively (P&nbsp;=&nbsp;.62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P&nbsp;=&nbsp;.81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P&nbsp;=&nbsp;.86) and 0.8 for placebo (P&nbsp;=&nbsp;.15; P&nbsp;=&nbsp;.31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P&nbsp;=&nbsp;.43) and 1.02 for placebo (P&nbsp;=&nbsp;.84; P&nbsp;=&nbsp;.44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP.ConclusionThis study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP

Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma

BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short ("stubby", ≤12 mm) and long ("stringy", &gt;12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs.CONCLUSIONPersistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy.TRIAL REGISTRATIONClinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDINGAstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative