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It is more common for educational and psychological data to be nonnormal than to be approximately normal. This tendency may lead to bias and error in point estimates of the Pearson correlation coefficient. In a series of Monte Carlo simulations, the Pearson correlation was examined under conditions of normal and nonnormal data, and it was compared with its major alternatives, including the Spearman rank-order correlation, the bootstrap estimate, the Box-Cox transformation family, and a general normalizing transformation (i.e., rankit), as well as to various bias adjustments. Nonnormality caused the correlation coefficient to be inflated by up to +0.14, particularly when the nonnormality involved heavy-tailed distributions. Traditional bias adjustments worsened this problem, further inflating the estimate. The Spearman and rankit correlations eliminated this inflation and provided conservative estimates. Rankit also minimized random error for most sample sizes, except for the smallest samples (n = 10), where bootstrapping was more effective. Overall, results justify the use of carefully chosen alternatives to the Pearson correlation when normality is violated.

The authors conducted a Monte Carlo simulation of 4 test statistics or comparing dependent correlations with no variables in common. Empirical Type 1 error rates and power estimates were determined for K. Pearson and L. N. G. Filon's (1898) z, O. J. Dunn and V. A. Clark's (1969) z, J. H. Steiger's (1980) original modification of Dunn and Clark's z, and Steiger's modification of Dunn and Clark's z using a backtransformed average z procedure for sample sizes of 10, 20, 50, and 100 under 3 different population distributions. For the Type 1 error rate analyses, the authors evaluated 3 different magnitudes of the predictor-criterion correlations (rho[subscript 12] = rho[subscript 34] = 0.10, 0.30, and 0.70). Likewise, for the power analyses, 3 different magnitudes of discrepancy or effect sizes between correlations with no variables in common (rho[subscript 12] and rho[subscript 14] were examined (values of 0.10, 0.40, and 0.60). All of the analyses were conducted at 3 different levels of predictor intercorrelation. Results indicated that the choice as to which test statistic is optimal, in terms of power and Type 1 error rate, depends not only on sample size and population distribution but also on (a) the predictor intercorrelations and (b) the effect size (for power) or the magnitude of the predictor-criterion correlations (for Type 1 error rate). For the conditions examined in the present study, Pearson and Filon's z had inflated Type 1 error rates when the predictor-criterion correlations were low to moderate. Dunn and Clark's z and the 2 Steiger procedures had similar, but conservative Type 1 error rates when the predictor-criterion correlations were low. Moreover, the power estimates were similar among the 3 procedures.

A Monte Carlo evaluation of four test statistics for comparing dependent zero-order correlations was conducted with four sample sizes and three population distributions. Results indicate that choice of optimal test statistic depends on sample size and distribution, and predictor intercorrelation and effect size or magnitude of the predictor-criterion correlations. (SLD)

Abstract Background Plasmodium falciparum malaria remains a leading cause of morbidity and mortality among African children. Innate immunity provides the first line of defence against P. falciparum infections, particularly in young children that lack naturally-acquired malarial immunity, such as the population examined here. Consistent with the fact that elevated interleukin (IL)-12 is an important component of the innate immune response that provides protective immunity against malaria, we have previously shown that suppression of IL-12 in African children is associated with the development of severe malarial anaemia (SMA). Since the role of IL12B variants in conditioning susceptibility to SMA remains largely unexplored, the association between a single nucleotide polymorphism (1188A→C, rs3212227), SMA (Hb Results Multivariate logistic regression analysis in children with acute malaria (n = 544) demonstrated that carriers of the C allele had increased susceptibility to SMA (CC: OR, 1.674; 95% CI, 1.006-2.673; P = 0.047, and AC: OR, 1.410; 95% CI, 0.953-2.087; P = 0.086) relative to wild type (AA). Although children with SMA had lower IL-12p40/p70 levels than the non-SMA group (P = 0.037), levels did not differ significantly according to genotype. Longitudinal analyses in the entire cohort (n = 756) failed to show any significant relationships between rs3212227 genotypes and either susceptibility to SMA or all-cause mortality throughout the three year follow-up. Conclusion The rs3212227 is a marker of susceptibility to SMA in children with acute disease, but does not appear to mediate functional changes in IL-12 production or longitudinal outcomes during the acquisition of naturally-acquired malarial immunity.

Cytokines and effector molecules are important immunoregulatory molecules in human malaria. Tumor necrosis factor (TNF)-α limits malaria parasitemia but also promotes pathogenesis at high concentrations, whereas prostaglandin E2 (PGE2) inhibits TNF-α production and is reduced in childhood malaria, at least in part, through suppression of cyclooxygenase (COX)-2 following the ingestion of Plasmodium falciparum hemozoin (pfHz; malarial pigment) by peripheral blood mononuclear cells (PBMCs). Although molecular interactions between TNF-α and PGE2 are largely unexplored in human malaria, results presented here show that pfHz-induced suppression of PBMC COX-2 gene products induces overproduction of TNF-α. Moreover, addition of exogenous PGE2 to pfHz-treated PBMCs dose-dependently decreased TNF-α production, whereas experimental COX inhibitors and antipyretics used during human malaria generated increased TNF-α production. Healthy, malaria-exposed children had elevated levels of circulating bicyclo-PGE2/TNF-α, compared with children with malarial anemia (P < .01), with systemic bicyclo-PGE2 and TNF-α significantly associated P < .01 with hemoglobin concentrations (r = 0.745; P < .01). The results of the present study illustrate that pfHz-induced suppression of PGE2 promotes overproduction of TNF-α, which is associated with enhanced malarial anemia. [ABSTRACT FROM AUTHOR]

Cytokines and effector molecules are important immunoregulatory molecules in human malaria. Tumor necrosis factor (TNF)-alpha limits malaria parasitemia but also promotes pathogenesis at high concentrations, whereas prostaglandin E2 (PGE2) inhibits TNF-alpha production and is reduced in childhood malaria, at least in part, through suppression of cyclooxygenase (COX)-2 following the ingestion of Plasmodium falciparum hemozoin (pfHz; malarial pigment) by peripheral blood mononuclear cells (PBMCs). Although molecular interactions between TNF-alpha and PGE2 are largely unexplored in human malaria, results presented here show that pfHz-induced suppression of PBMC COX-2 gene products induces overproduction of TNF-alpha. Moreover, addition of exogenous PGE2 to pfHz-treated PBMCs dose-dependently decreased TNF-alpha production, whereas experimental COX inhibitors and antipyretics used during human malaria generated increased TNF-alpha production. Healthy, malaria-exposed children had elevated levels of circulating bicyclo-PGE2/TNF-alpha, compared with children with malarial anemia (P<.01), with systemic bicyclo-PGE2 and TNF-alpha significantly associated with hemoglobin concentrations (r=0.745; P<.01). The results of the present study illustrate that pfHz-induced suppression of PGE2 promotes overproduction of TNF-alpha, which is associated with enhanced malarial anemia. [ABSTRACT FROM AUTHOR]

Background: The molecular immunological interactions between HIV and malaria are largely undefined. Since tumor necrosis factor (TNF)-alpha is elevated during acute malaria and increases with HIV-1 disease progression, TNF-alpha production may be an important mediator for interactions between malaria and HIV-1., Methods: To examine the stage-specific immunological interactions between HIV and malaria, peripheral blood mononuclear cells (PBMC) and CD14 cells were isolated and cultured from rhesus macaques at different stages of SIV infection. Cultures were stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma in the presence of Plasmodium falciparum-derived hemozoin (Hz) or synthetic Hz (sHz). TNF-alpha transcripts and soluble protein were examined by real time reverse transcription-PCR and ELISA, respectively. The effects of Hz on viral replication were determined by measurement of p27 antigen with varying concentrations of TNF-alpha neutralizing antibodies., Results: Hz and sHz significantly increased LPS- and IFN-gamma-induced TNF-alpha protein and transcripts in PBMC from animals with late stage SIV infection (i.e., AIDS). Hz and sHz also induced high levels of sustained TNF-alpha transcripts in PBMC from the AIDS group. During the late stage of disease, CD14 cells were the primary source of TNF-alpha production. Stimulation of PBMC with Hz and sHz significantly increased viral replication that was dose-dependently reduced by the addition of TNF-alpha neutralizing antibodies., Conclusions: Hz promotes high levels of TNF-alpha production from PBMC during AIDS and increases viral replication in SIV-infected animals.

Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with Plasmodium falciparum malaria has not previously been reported, circulating levels of beta-chemokines (MIP-1alpha, MIP-1beta, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1alpha and MIP-1beta levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. Beta-chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating beta-chemokines, illustrating that PBMCs are a primary source for the observed pattern of beta-chemokine production during acute malaria. Statistical modeling revealed that none of the chemokines was significantly associated with either parasitemia or anemia. Additional investigations in healthy children with a known history of malaria showed that children with prior severe malaria had significantly lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in the ability to produce RANTES in these two groups. Baseline MIP-1alpha and MIP-1beta did not significantly differ between children with prior severe malaria and those with mild malaria. Additional in vitro experiments in PBMCs from healthy, malaria-naïve donors revealed that P. falciparum-derived hemozoin (Hz; malarial pigment) and synthetic Hz (beta-hematin) promote a similar pattern of beta-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of beta-chemokines characterized by increased circulating levels of MIP-1alpha and MIP-1beta and decreased RANTES. Altered patterns of circulating beta-chemokines result, at least in part, from Hz-induced changes in beta-chemokine gene expression in blood mononuclear cells.