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D McGuinness

Publications and source records attributed to D McGuinness.

17 recordsLinked to original sources
PubMed1997

Statistical analysis of highly skewed immune response data.

This paper considers methods of statistical analysis for highly skewed immune response data. Observations from population studies of immunological variables are rarely normally distributed between individuals; typically the distribution shows extreme levels of skewness. In some situations, skewness remains considerable even after transforming the data. Using resampling techniques, applied to several actual datasets of ELISA assay data, we consider the robustness of normal parametric methods, e.g. t tests and linear regression. Despite the skewness of the transformed data, we demonstrate that such methods are quite robust depending on the number of observations, type of analysis and severity of skewness. We also illustrate how bootstrap resampling can be used to provide a valid alternative method of analysis that can be used either for checking normal parametric analysis or as a direct method of analysis. We illustrate this combined approach by analysing real data to test for association between human serum antibodies to malaria merozoite surface proteins, MSP1 and MSP2, and resistance to clinical malaria, and confirm the protective effect of antibodies to MSP1 and demonstrated a similar protective effect for some antibodies to MSP2.

Animals↗
PubMed1997

Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune human sera is associated with antibodies to the gamete surface antigen Pfs230.

Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mosquitoes; these antigens have been proposed as candidates for inclusion in a malaria transmission-blocking vaccine. One possible mechanism of antibody-mediated transmission blocking is complement-mediated gamete lysis. We have used a panel of human sera from geographically distinct regions where malaria is endemic to investigate whether this may be a mechanism of naturally acquired transmission-blocking immunity to P. falciparum. By immunoprecipitation, we have shown that antibody recognition of Pfs230 and Pfs48/45 is limited, despite universal exposure to P. falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum gametes was positively associated with the presence of antibodies to Pfs230 but not with antibodies to the N-terminal region of the precursor molecule (Pfs260), which is shed from the gametocyte surface at the time of gametogenesis. Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and Pfg27/25, were not associated with gamete lysis. All sera which mediate gamete lysis contain immunoglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface proteins as determined by an enzyme-linked immunosorbent assay. These data suggest that Pfs230 is a major target of complement-fixing antibodies which may be important for antibody-mediated transmission-blocking immunity.

Adolescent↗
PubMed1996

Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting.

Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Ps260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness. Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults. Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes of the same protein. An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin).

Adult↗
PubMed1995

Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids.

Patients with beta-thalassemia major often have pubertal delay, the etiology of which has not been fully elucidated. We investigated the pituitary-gonadal response to short-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five young males (aged 13.6-19.0 years) affected by beta-thalassemia major and presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin levels were determined and their isoform profiles were examined, before and after GnRH treatment, in a pool of samples collected every 15 min for 240 min. Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone and 17 beta-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5 and 7 of treatment. Five patients (aged 16.9-26.8 years) with confirmed diagnosis of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH therapy were also studied in the same protocol. Increased sex steroid levels were observed in both groups as a result of treatment. On day 7, the thalassemic patients had increased bioactive luteinizing hormone (LH) and follide-stimulating hormone (FSH), although immunoreactive LH and FSH were comparable to day 0. Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were noted in LH profiles on day 7. Similar results were observed in hypogonadal patients, who also had increased immunoreactive LH and FSH values. We suggest that the early stage of delayed puberty in thalassemia might be characterized by a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release, which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment seems to re-establish partially the correct pituitary-gonadal function.

17-alpha-Hydroxyprogesterone↗
PubMed1993

Assessment of psychosocial experiences in childhood: methodological issues and some illustrative findings.

The development of a new standardised investigator-based interview, PACE (Psychosocial Assessment of Childhood Experiences), for the assessment of acute life events and long-term psychosocial experiences is described. An application of PACE to a sample of 84 children referred to psychiatric clinics and 22 general population controls, is presented. Reliability was assessed using a separate clinic sample of 15 child-parent pairs. The findings showed that PACE has satisfactory reliability and discriminant validity.

Adaptation, Psychological↗
PubMed1992

Attention and para-attentional processing. Event-related brain potentials as tests of a model.

In 1972 when we began to analyze the vast amount of material from the laboratories of physiological psychologists, we had only a vague conceptualization of what a model of attention might look like. We began where everyone else had, with the view that everything had something to do with "arousal" but with Lacey's (1967) warning in mind that all of the dependent variables might not actually be measuring aspects of the same process. With this warning in mind, we were forced by the data to organize them into a three-systems mode. Since the first publication of this model in 1975, we have found increasing amounts of evidence to support and extend it. This evidence is briefly reviewed in the present paper in terms of the techniques employed in various types of investigation. Further, the current review of data has made it possible to specify the para-attentional substrate (the extrinsic lemniscal primary projection systems) upon which the three systems described in the earlier model operate. The earlier model was based on psychophysiological, neurobehavioral and neurochemical analyses while the current specification results from the results of recordings of event-related brain electrical responses. The conclusions derived from these results can be summarized as follows: First. It has become possible to distinguish controlled attention from the para-attentional pre- and post-attentive automatic processes upon which controls operate. Second. The pre- and post-attentive processes appear to be coordinate with activity in the extrinsic lemniscal primary sensory projection systems. Processing in these systems is reflected in the early components of event-related brain electrical potentials. These extrinsic systems are, however, not just throughputs for further processing. Rather, they are sensitive to the history of reinforcement which the subject has experienced. The concept of a limited channel capacity must, therefore, be modified to encompass this ability of organisms to improve, through practice, their competence to process a great deal of information in parallel. Competence, not capacity, limits central processing span. Third. A set of intrinsic extralemniscal processing systems has been identified to operate via a tecto-tegmental pathway to the reticular nucleus of the thalamus. The later components (N2P3, etc.) of event-related potentials have been shown to reflect processing in these systems and those that control them. Activity in these systems has been related to targeted conscious awareness.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗
PubMed1982

Lateral asymmetry: hard or simple-minded?

A letter or a three-dimensional shape was presented in the center of the visual field. Following the off-set of this stimulus either a comparison letter or a three-dimensional shape was flashed briefly in either the right or left visual field. The subject's task was to respond SAME, or DIFFERENT. The stimuli could be in the same plane, rotated in two dimensions (letters) or in three dimensions (three-dimensional shapes). The left visual field presentations (right hemisphere) of same-pair matches for letters only produced faster reaction times and fewer errors. In all other conditions reaction time measures showed no hemisphere effects. By contrast, error score data indicated that the left hemisphere was overwhelmingly more accurate.

Adolescent↗
PubMed1980

A decisional analysis of the effects of inferotemporal lesions in the rhesus monkey.

Modified signal detection procedures were used to analyze the effects of inferotemporal cortical resections. The results demonstrated (a) a severe difficulty in responding to differences in luminance; (b) a severe difficulty in responding to differences in luminance; (b) a small but consistent change in sensitivity (d'), which is attributed to an increased sensitivity to noise or a deficiency in the suppression of irrelevant aspects of the environment; and (c) an enhanced bias to respond to a nonrewarded stimulus (a lowering of criterion). This altered bias contrasts with the results obtained from limbic resections in a previous experiment which produced a marked increase in bias to a rewarded contingency without influencing discrimination or detection.

Animals↗
PubMed1977

The effect of chronic anxiety level upon self control of heart rate.

A sample of 90 subjects were rated on the IPAT anxiety scale and 5 subjects (3 male and 2 female) per group were selected from each of the high and low anxiety categories. All subjects were naive participants in heart rate biofeedback sessions utilising analogue visual feedback. Following a heart rate baseline (no feedback) session, all subjects were required to raise their heart rate and lower their heart rate in two separate trials, a visual "target" criteria being provided. The data collected consisted of a resting baseline heart rate value, mean heart rate increase, and mean heart decrease values expressed as beats per minute. Results indicated a marked ability for highly anxious subjects to self-induce heart rate increases only and for low anxious subjects to decrease their heart rate only.

Anxiety↗
PubMed1976

Away from a unisex psychology: individual differences in visual sensory and perceptual processes.

Four tests of visual perception were given to twenty-five men and twenty-five women. These were a test of acuity, threshold for four field positions, visual persistence, and a measure of comfortable brightness. Subjects also completed five personality questionnaires. In most measures, differences were found to be related to sex rather than to personality factors. In fact, the analyses performed suggest that persenality tests do not measure equivalent processes in men and women. Correlational anaylsis showed all visual functions to be independent of one another with the exception of photopic acuity and scotopic threshold, which were highly correlated. Two new findings on the visual system emerged which have not been reported elsewhere: (i) Four distinct dark adaptation curves were produced, and have been labeled as exponential, flat-exponential, linear, and plateau. All subjects fell into one of these categories and showed a consistent trend to exhibit these curves for all field positions. (ii) Highly significant differences were found in sensitivity for the four visual fields, the upper field was superior, followed by the right, then left, with the lower visual field considerably poorer.

Adolescent↗
PubMed1976

Sex differences in visual persistence: experiments on the Ganzfeld and afterimages.

Sex differences were investigated in two experiments on visual persistence: the Ganzfeld and the afterimage. Males were found to hold visual sensation longer than females, particularly in the Ganzfeld where there was little overlap of scores. Variability of experience in the Ganzfeld was also greater for males and they commonly reported 'blank-out' effects while females did not. There was further evidence from both experiments that females are more responsive to the long-wave region of the frequency spectrum.

Adolescent↗