The asthmatic athlete, inhaled beta agonists, and performance

INTRODUCTION: The large increase in the number of athletes who apply to use inhaled beta agonists (IBAs) at the Olympic Games is a concern to the medical community. This review will examine the use of IBAs in the asthmatic athlete, the variability that exists between countries and sport, and outline a plan to justify the use of these medications. DATA SOURCES: Much of this article is a result of an International Olympic Committee (IOC) Medical Commission-sponsored meeting that took place in May 2001. Records of the use of IBAs at previous Olympics were reviewed. MEDLINE Searches (PubMed interface) were performed using key words to locate published work relating to asthma, elite athletes, performance, treatment, and ergogenic aids. MAIN RESULTS: Since 1984 there have been significant increases in the use of IBAs at the Olympic Games as well as marked geographical differences in the percentage of athletes requesting the use of IBAs. There are large differences in the incidence of IBA use between sports with a trend towards increased use in endurance sports. There are no ergogenic effects of any IOC-approved IBA given in a therapeutic dose. CONCLUSIONS: In many cases, the prescription of IBAs to this population has been made on empirical grounds. Beginning with the 2002 Winter Games, athletes will be required to submit to the IOC Medical Commission clinical and laboratory evidence that justifies the use of this medication. The eucapnic voluntary hyperpnea test will be used to assess individuals who have not satisfied an independent medical panel of the need to use an IBA.

Factor analysis of the Self Report Version of the Strengths and Difficulties Questionnaire in a sample of children with intellectual disability

The rate of emotional and behavioral disturbance in children with intellectual disability (ID) is up to four times higher than that of their typically developing peers. It is important to identify these difficulties in children with ID as early as possible to prevent the chronic co-morbidity of ID and psychopathology. Children with ID have traditionally been assessed via proxy reporting, but appropriate and psychometrically rigorous instruments are needed so that children can report on their own emotions and behaviors. In this study, the factor structure of the self-report version of the Strengths and Difficulties Questionnaire (SDQ) was examined in a population of 128 children with ID (mean age = 12 years). Exploratory and Confirmatory Factor Analysis showed a three factor model (comprising Positive Relationships, Negative Behavior and Emotional Competence) to be a better measure than the original five factor SDQ model in this population.

Reducing road related injuries for young adolescents : an investigation of truancy as a risk factor

Truancy is recognised as an indicator of engagement in high-risk behaviours for adolescents. Injuries from road related risk behaviours continue to be a leading cause of death and disability for early adolescents (13-14 years). The aim of this research is to determine the extent to which truancy relates to increased risk of road related injuries for early adolescents. Four hundred and twenty-seven Year 9 students (13-14 years) from five high schools in Queensland, Australia, completed a questionnaire about their perceptions of risk and recent injury experience. Self-reported injuries were assessed by the Extended Adolescent Injury Checklist (E-AIC). Injuries resulting from motorcycle use, bicycle use, vehicle use (as passenger or driver), and as a pedestrian were measured for the preceding three months. Students were also asked to indicate whether they sought medical attention for their injuries. Truancy rates were assessed from self-reported skipping class or wagging school over the same three month period. The findings explore the relationship between early adolescent truancy and road related injuries. The relationship between road related injuries and truancy was analysed separately for males and females. Results of this study revealed that road related injuries and reports of associated medical treatment are higher for young people who engage in truancy when compared with non-truant adolescents. The results of this study contribute knowledge about truancy as a risk factor for engagement in road related risks. The findings have the potential to enhance school policies and injury prevention programs if emphasis is placed on increasing school attendance as a safety measure to decrease road related injuries for young adolescents.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology

Tumour necrosis factor (TNF) is a pleiotropic cytokine with dual roles in cancer biology including prostate cancer (PCa). On the one hand, there is evidence that it stimulates tumour angiogenesis, is involved in the initiation of PCa from an androgen-dependent to a castrate resistant state, plays a role in epithelial to mesenchymal plasiticity, and may contribute to the aberrant regulation of eicosanoid pathways. On the other hand, TNF has also been reported to inhibit neovascularisation, induce apoptosis of PCa cells, and stimulate anti-tumour immunity. Much of the confusion surrounding its seemingly paradoxical roles in cancer biology stems from the dependence of its effects on the biological model within which TNF is investigated. This review will address some of these issues, and also discuss on the therapeutic implications.

Scaffolds for growth factor delivery as applied to bone tissue engineering

There remains a substantial shortfall in treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient, has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors; which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However cost and potential complications associated with growth factors means controlled release is an important consideration in the design of new bone tissue engineering strategies. This review will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5

Murine intestinal intraepithelial lymphocytes (IEL) have been shown to contain subsets of alpha/beta TCR+ and gamma/delta TCR+ T cells that spontaneously produce cytokines such as IFN-gamma and IL-5. We have now determined the nature and cell cycle stage of these cytokine-producing T lymphocytes in EIL by using IFN-gamma- and IL-5-specific ELISPOT assay, cytokine-specific mRNA-cDNA dot-blot hybridization and polymerase chain reaction, and flow cytometry (FACS) for DNA analysis. When CD3+ T cells from IEL of normal C3H/HeN mice were separated into low and high density fractions by discontinuous Percoll gradients, IFN-gamma and IL-5 spot-forming cells were only found in the former population. Analysis of mRNA for these cytokines by both IFN-gamma- and IL-5-specific dot-blot hybridization and polymerase chain reaction revealed that higher levels of message for IFN-gamma and IL-5 were also seen in the low density fraction. However, cell cycle analysis of these two fractions by FACS using propidium iodide showed a similar pattern of cell cycle stages in both low and high density populations (G0 + G1 approximately 96 to 98% and S/G2 + M approximately 2 to 4%). Finally, mRNA from gamma/delta TCR+ and alpha/beta TCR+ T cells in both low and high density fractions of IEL were analyzed for IFN-gamma and IL-5 message by polymerase chain reaction. After 35 cycles of amplification, both gamma/delta TCR+ and alpha/beta TCR+ T cells in the low density fraction expressed higher levels of message for these two cytokines when compared with the high density population. These results have now shown that both gamma/delta and alpha/beta TCR+ IEL can be separated into low and high density subsets and both fractions possess a similar stage of cell cycle. However, only the low density cells (in G1 phase) of both gamma/delta and alpha/beta TCR types possess increased cytokine-specific mRNA and produce the cytokines IFN-gamma and IL-5. Our results suggest that alpha/beta TCR+ and gamma/delta TCR+ IEL can produce cytokines without cell proliferation.

The factor structure of the COPE Questionnaire in a sample of clinically depressed and anxious adults

The Coping Orientation to Problems Experienced is a multidimensional scale designed to assess how people respond to stress. The COPE has been validated in a variety of populations displaying variations in factor structure. However, in terms of mental health populations, it has only been validated in alcohol-dependent samples. This paper investigated the factor structure of the COPE in a sample of adults diagnosed with depression and anxiety. Two hundred and seventy-one patients attending cognitive behaviour therapy for anxiety and depression completed the COPE. Confirmatory factor analysis found a poor fit for both lower order and higher order factors based upon the Lyne and Roger (2000) study. Exploratory factor analyses identified six primary subscales (Active Planning, Social Support, Denial, Acceptance, Disengagement, Restraint) which explained approximately 60% of the variance in coping. These 6 subscales may assist researchers and clinicians to validly measure coping in anxious and depressed adults.

Teacher Reporting Attitudes Scale (TRAS): confirmatory and exploratory factor analyses with a Malaysian sample.

The Teacher Reporting Attitude Scale (TRAS) is a newly developed tool to assess teachers’ attitudes toward reporting child abuse and neglect. This article reports on an investigation of the factor structure and psychometric properties of the short form Malay version of the TRAS. A self-report cross-sectional survey was conducted with 667 teachers in 14 randomly selected schools in Selangor state, Malaysia. Analyses were conducted in a 3-stage process using both confirmatory (stages 1 and 3) and exploratory factor analyses (stage 2) to test, modify, and confirm the underlying factor structure of the TRAS in a non-Western teacher sample. Confirmatory factor analysis did not support a 3-factor model previously reported in the original TRAS study. Exploratory factor analysis revealed an 8-item, 4-factor structure. Further confirmatory factor analysis demonstrated appropriateness of the 4-factor structure. Reliability estimates for the four factors—commitment, value, concern, and confidence—were moderate. The modified short form TRAS (Malay version) has potential to be used as a simple tool for relatively quick assessment of teachers’ attitudes toward reporting child abuse and neglect. Cross-cultural differences in attitudes toward reporting may exist and the transferability of newly developed instruments to other populations should be evaluated.

A confirmatory factor analysis of the Observer Alexithymia Scale in treatment seeking alcohol-dependent patients

Confirmatory factor analyses evaluated the factorial validity of the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample. Observation was conducted by clinical psychologists. All models examined were rejected, given their poor fit. Given the psychometric limitations of the OAS shown in this study, the OAS may not be the most appropriate measure to use early in treatment among alcohol-dependent individuals.

University Student Depression Inventory (USDI) : confirmatory factor analysis and review of psychometric properties

Background: The 30-item USDI is a self-report measure that assesses depressive symptoms among university students. It consists of three correlated three factors: Lethargy, Cognitive-Emotional and Academic motivation. The current research used confirmatory factor analysis to asses construct validity and determine whether the original factor structure would be replicated in a different sample. Psychometric properties were also examined. Method: Participants were 1148 students (mean age 22.84 years, SD = 6.85) across all faculties from a large Australian metropolitan university. Students completed a questionnaire comprising of the USDI, the Depression Anxiety Stress Scale (DASS) and Life Satisfaction Scale (LSS). Results: The three correlated factor model was shown to be an acceptable fit to the data, indicating sound construct validity. Internal consistency of the scale was also demonstrated to be sound, with high Cronbach Alpha values. Temporal stability of the scale was also shown to be strong through test-retest analysis. Finally, concurrent and discriminant validity was examined with correlations between the USDI and DASS subscales as well as the LSS, with sound results contributing to further support the construct validity of the scale. Cut-off points were also developed to aid total score interpretation. Limitations: Response rates are unclear. In addition, the representativeness of the sample could be improved potentially through targeted recruitment (i.e. reviewing the online sample statistics during data collection, examining the representativeness trends and addressing particular faculties within the university that were underrepresented). Conclusions: The USDI provides a valid and reliable method of assessing depressive symptoms found among university students.

Advanced practice nursing role development : factor analysis of a modified role delineation tool

Aim his study reports the use of exploratory factor analysis to determine construct validity of a modified advanced practice role delineation tool. Background Little research exists on specific activities and domains of practice within advanced practice nursing roles, making it difficult to define service parameters of this level of nursing practice. A valid and reliable tool would assist those responsible for employing or deploying advanced practice nurses by identifying and defining their service profile. This is the third paper from a multi-phase Australian study aimed at assigning advanced practice roles. Methods A postal survey was conducted of a random sample of state government employed Registered nurses and midwives, across various levels and grades of practice in the state of Queensland, Australia, using the modified Advanced Practice Role Delineation tool. Exploratory factor analysis, using principal axis factoring was undertaken to examine factors in the modified tool. Cronbach’s alpha coefficient determined reliability of the overall scale and identified factors. Results There were 658 responses (42% response rate). The five factors found with loadings of ≥.400 for 40 of the 41 APN activities were similar to the five domains in the Strong model. Cronbach’s alpha coefficient was .94 overall and for the factors ranged from 0.83 to 0.95. Conclusion Exploratory factor analysis of the modified tool supports validity of the five domains of the original tool. Further investigation will identify use of the tool in a broader healthcare environment.

A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis

The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear. Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor (IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof during insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measured using qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolonged euglycaemic, hyperinsulinaemic clamp (p-EHC), during the mid-developmental (24 h) and acute (46 h) phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13–32-fold (P < 0.05) at both time-points in the insulin-treated horses. A second aim was to determine if the down-regulation of the receptor genes could be accounted for by an increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horses given a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution. There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulation of both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriate lamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemic laminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapy for hyperinsulinaemic laminitis.

Insulin and the insulin-like growth factor system : a novel theory for hyperinsulinemic laminitis pathogenesis

Research into hyperinsulinemic laminitis has progressed significantly in recent years with the use of the prolonged-euglycemic, hyperinsulinemic clamp (p-EHC). Previous investigations of laminitis pathophysiology have focused on digital vascular dysfunction, inflammation, altered glucose metabolism within the lamellae, and lamellar basement membrane breakdown by metalloproteinases. The etiopathogenesis of laminitis occurring in association with hyperinsulinemia is yet to be fully characterized, but it may not involve these mechanisms. Insulin stimulates cellular proliferation and can also affect other body systems, such as the insulin-like growth factor (IGF) system. Insulin-like growth factor-1 (IGF-1) is structurally homologous to insulin and, like insulin, binds with strong affinity to a specific tyrosine kinase receptor on the cell surface to produce its effects, which include promoting cell proliferation. Receptors for IGF-1 (IGF-1R) are present in the lamellar epidermis. An alternative theory for the pathogenesis of hyperinsulinemic laminitis is that uncontrolled cell proliferation, mediated through both the insulin receptor (InsR) and IGF-1R, leads to lengthening, weakening, and failure of the lamellae. An analysis of the proliferative activity of lamellar epidermal cells during the developmental and acute phases of hyperinsulinemic laminitis, and lamellar gene expression of the InsR and IGF-1R was undertaken.

What drives the commodity price beta of oil industry stocks

We test theoretical drivers of the oil price beta of oil industry stocks. The strongest statistical and economic support comes for market conditions-type variables as the prime drivers: namely, oil price (+), bond rate (+), volatility of oil returns (−) and cost of carry (+). Though statistically significant, exogenous firm characteristics and oil firms' financing decisions have less compelling economic significance. There is weaker support for the prediction that financial risk management reduces the exposure of oil stocks to crude oil price variation. Finally, extended modelling shows that mean reversion in oil prices also helps explain cross-sectional variation in the oil beta.