Bibliography: pages 55-61. / A critical evaluation of research investigating the uses of the Trail Making Test (TMT) with children and adults was undertaken. Uses of the TMT in neuropsychological and other clinical settings, as well as the relationship of TMT performance to subject and experimenter variables were considered. A shortened version of the TMT developed for children was administered to 260 normal children, between the ages of 10 years and 14 years 11 months, to examine the relationship of TMT performance to age, full scale intelligence quotient and' gender variables. Comparisons of descriptive data relating to TMT performance were made between the present study and previous research of a analysis (multivariate analysis analysis) showed increasing age performance on Part A and Part findings for further clinical similar nature. Further statistical of variance and multiple regression and FSIQ to be associated with quicker B of the TMT. The implications of these use with the TMT, were considered. Limitations of the present study, in conjunction with suggestions for further research, were discussed.

Bibliography: pages 142-149. / This study may be divided roughly into two sections: a general outline of the infertility field of study, and an empirical investigation of psychological differences between various infertility subgroups. In the outline, specific reference has been made to practical and conceptual problems inherent in the diagnosis of infertility, as these have bearing on the type of research that necessitates a division of infertile subjects into subgroups. An attempt has been made to clearly delineate and describe the possible subgroups under the broad categories of organic and functional diagnoses. Theoretical and diagnostic inconsistencies with regard to the latter group have been discussed in some detail, to arrive at an exact definition. In this respect the psychosomatic model of medicine has been introduced as a point of reference. An overview has been presented of the literature which focuses on psychological aspects of infertility. Attitudes towards, and empirical investigations of psychological factors associated with infertility have been critically discussed. Taking into account some of the biases and errors of previous research, the empirical study was designed to investigate hypothesized psychological differences between respective organically infertile and functionally infertile experimental groups and a fertile control group of married couples. Particular dimensions assessed were interactional family functioning and discrepancies in mutual perceptions between respective husbands and wives. The McMaster Family Assessment Device and the Semantic Differential technique were used as measures of these respective dimensions, and these were administered to both partners. No significant differences were found between any of the groups investigated. On the basis of the findings of the present study and much of the previous research in the field, the basic assumptions that psychopathological factors may be associated with infertility, especially in the case of a functional diagnosis, have been questioned. The counselling and crisis intervention models were proposed as a more appropriate way in which to understand the emotional problems of infertile couples.

Includes abstract. / Includes bibliographical references. / The pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol in 78 patients with tuberculosis were described using non-linear mixed effects modeling. Pharmacodynamic data was comprised of weekly sputum liquid culture (using mycobacterial growth indicator tubes) time to detection results from 144 patients during the first 2 months of treatment. The effect of drug exposure on patient outcomes was investigated. To determine the adequacy of ofloxacin drug exposure, the probability of attaining the required area-under-the-curve to minimum inhibitory concentration ratio (AUC/MIC) of ofloxacin was determined in 65 patients on treatment for multidrug resistant tuberculosis. To improve efficiency in the clinical development of new drug regimens, clinical trial simulation was used to determine the optimal study design for a study investigating the efficacy of a new antitubercular drug regimen. The SLCO1B1 rs4149032 polymorphism existed at a high frequency of 0.70 in South Africans and resulted in a 28% decrease in bioavailability of rifampicin. The rifampicin peak concentration was a significant predictor of the 2 month treatment outcomes. A semimechanistic time to event model was developed to analyze days to positivity (time to detection) data. The model was comprised of a biexponential decay model describing bacillary decline in sputum from patients, followed by a logistic model with a lag time for growth of the mycobacteria in liquid culture. For the current 800 mg daily dose of ofloxacin, the probability of attaining an AUC/MIC target ratio of at least 100 was only 0.45. Based on clinical trial simulation, the optimum parallel study design was comprised of 125 study participants in each of 2 arms to achieve a study power of at least 80%. Increasing the study length beyond 42 days reduced study power perhaps due to increased amounts of censored data. Higher doses of rifampicin are required in the majority of South African patients with tuberculosis. A novel pharmacodynamic model of tuberculosis treatment is presented, which can be used for investigation of covariates such as drug exposure. Ofloxacin should be replaced with a more potent fluoroquinolone for treatment of multidrug resistant tuberculosis. Clinical trials should not be unduly long otherwise this may compromise study power.

Emotion regulatory problems in children, such as uncontrollable tantrums, kicking, and screaming, are a concern for parents. When parents and caregivers have no tools at their disposal to deal effectively with this, they may resort to physical measures of discipline, which may lead to physical abuse and also have negative effects on the wellbeing of the child. There is a need for a set of skills for what to do during these crisis moments. However, the state of evidence on this is unknown. Thus, a systematic review of interventions for emotionally dysregulated children was conducted in order to ascertain the state of evidence and to provide parents, teachers, hospital staff and caregivers with a "toolbox" of skills they can use. The findings of the studies indicated that the skills worked when used in a noncoercive manner. Overall the quality of the studies was weak: most were single-case studies. This review provides tentative suggestions of skills that parents and caregivers may find useful with dysregulated children, but further research into the effectiveness of these skills is needed.

The recurring challenge of the emergence of drug resistance necessitates the continual development of improved antimalarial treatments, which can target parasite strains that display reduced susceptibility towards current therapy. Consequently, a novel series of dual functioning pyridodibemequine (PDBQ) compounds were designed with the intention of reversing resistance in chloroquine-resistant (CQR) strains of Plasmodium falciparum. These hybrid molecules integrate a 4-amino-7-chloroquinoline antiplasmodial core with a modified dibenzylmethylamine side chain, which interacts with the CQR mutant P. falciparum chloroquine resistance transporter (PfCRT) to hinder the efflux of chloroquine (CQ) from its site of action, thereby reversing CQ resistance. The parent compounds of the PDBQ series, which differ in the ortho-, meta-, and para-orientation of the dibenzylmethylamine side chain, displayed favourable in vitro potency against chloroquine-sensitive (CQS) and CQR strains of P. falciparum; however, they were shown to be metabolically labile. Structure elucidation demonstrated that all formed PDBQ metabolites retained the 4-amino-7-chloroquinoline pharmacophore of the parent. Thus, the major metabolites, M1 and M2, generally conserved the in vitro antimalarial activity and selectivity of the parent compounds. Mechanistic studies revealed that the antiplasmodial activity of the PDBQ parent compounds and major metabolites primarily results from the inhibition of haemozoin formation, culminating in a toxic accumulation of ferriprotoporphyrin IX. The parents and major metabolites exhibited minimal toxicity against a mammalian cell line, and the metabolites are proposed to display reduced systemic toxicity, and human ether-a-go-go-related gene liability compared to the parent compounds. Furthermore, the major metabolites generally exhibited similar or improved in vitro solubility, permeability, lipophilicity, and metabolic stability compared to the parent compounds. Therefore, given their favourable in vitro characteristics, the major active metabolites of each parent PDBQ compound were further evaluated in this project to determine their potential as early preclinical antimalarial lead candidates. The proof of concept study presented herein investigated the in vivo pharmacokinetics (PK) of the PDBQ series of parents and major metabolites in a healthy murine model to allow the rational selection of candidates to be evaluated for their in vivo antimalarial efficacy and PK in a P. falciparum-infected murine model. For the PK studies in healthy and malaria-infected mice, analyte detection from whole blood was achieved using high-performance liquid chromatography coupled to tandem mass spectrometry. The bioanalytical methods were developed and partially validated based on a fit-for-purpose approach, which ensured that the generated PK concentration data was reliable and accurate. Lastly, given the significance of combination therapy in delaying the onset of drug resistance, fixed-dose ratio isobologram analyses were performed to probe the potential of the lead candidates to be used synergistically with an antimalarial partner drug possessing a distinct mechanism of action to haemozoin inhibition. Additionally, the ability of the lead candidates to reverse CQ resistance was evaluated in a CQR strain of P. falciparum. A comparative PK study was performed in a healthy murine model to determine whether the parent PDBQ compound should be used as a strategy to deliver the active metabolites or whether the active major metabolite should be directly administered. This was achieved by oral administration of the parent PDBQ compound and subsequent quantification of the parent compound and formation of the major metabolites. In addition, each pre-synthesised major metabolite was orally administered, at the equivalent parent dose, to characterise the PK profile of the individual active metabolite. These PK studies revealed that the overall oral exposure of the antimalarial pharmacophore was markedly greater after direct administration of the preformed metabolite compared to the cumulative oral exposure of the parent and formed metabolites after administration of the parent PDBQ compound. Furthermore, the metabolites attained higher maximal concentrations and maintained circulating concentrations which favourably exceeded their respective in vitro half-maximal inhibitory concentration at 24 h post-oral administration compared to the parent compounds at the equivalent oral dose. These findings substantiated the direct administration of the preformed PDBQ major metabolite over the parent compound. From the series of PDBQ metabolite derivatives, compounds 43M1 and 47M1 displayed the highest maximal concentrations of 8 ± 1 and 9.4 ± 0.5 μM, respectively and the greatest oral exposures of 62 ± 3 and 93 ± 9 µM.h, respectively, after single 20 mg/kg oral administrations of either 43M1 or 47M1. Given their encouraging PK profiles, 43M1 and 47M1 were selected to progress to the subsequent phase of the study which evaluated their in vivo antimalarial efficacy and pharmacokinetic/pharmacodynamic (PK/PD) relationship in a P. falciparum-infected humanised murine model. 43M1 and 47M1 were efficacious against asexual intraerythrocytic P. falciparum infection in humanised mice, where both compounds displayed a 98% reduction in parasitaemia after 4 consecutive daily oral administrations of 20 mg/kg of either 43M1 or 47M1 compared to the untreated control. The PK/PD analysis revealed dose-dependent reductions in parasitaemia; and the doses required to produce 90% of the maximal parasiticidal response (ED90) were 12 and 7.7 mg/kg for 43M1 and 47M1, respectively. Additionally, the oral exposures required to achieve the effect at the ED90 were 6.2 and 18.6 µM.h for 43M1 and 47M1, respectively. 43M1 or 47M1 demonstrated overall in vitro antimalarial synergy with dihydroartemisinin or atovaquone and additivity with methylene blue in CQS and CQR strains of P. falciparum. 43M1 or 47M1 with mefloquine or lumefantrine displayed in vitro antimalarial synergy in a CQS strain of P. falciparum; however, in a CQR strain, antagonism and additivity were displayed with mefloquine and lumefantrine, respectively. Additionally, 43M1 and 47M1 were unable to potentiate the in vitro antiplasmodial activity of CQ in a CQR strain of P. falciparum which suggested that, unlike the parent PDBQ compound, the metabolite did not possess the ability to reverse CQ resistance. The promising in vivo antimalarial efficacy of 43M1 and 47M1 against P. falciparum and their prospective in vitro antimalarial synergy with dihydroartemisinin and atovaquone underlines the potential of 43M1 and 47M1 for further development as preclinical antimalarial candidates.

Studies conducted in the area of burns have recently begun to document the psychological implications of the condition. Burn survivors are often reported to suffer from post-traumatic stress disorder, depression, and social withdrawal. Difficulties in the self-concept domain have also been reported. No study in the country has captured the incidence of burns and its consequences, from the caregivers' perspective. It is this group of people that have been identified as playing a vital role in the child's recovery and adjustment. It is this same group that is also considered to be at high risk for experiencing ""caregiver burden"" linked with caring for the ill child.

No description available.

Includes bibliographical references. / Globally Sub-Saharan Africa carries the biggest burden of patients infected with human immunodeficiency virus (HIV). Tuberculosis is the most common opportunistic infection in patients infected with HIV. Although antiretroviral therapy (ART) has decreased the burden of tuberculosis in HIV-infected patients, the incidence of tuberculosis remains higher than in the general population. HIV-tuberculosis co-infection requires dual treatment with ART and tuberculosis treatment, exposing patients to multiple drug-drug interactions. As ART programs mature, more patients will be changed from first-line to second-line ART. In South Africa, the adult second-line ART consists of the protease inhibitor (PI) lopinavir/ritonavir (LPV/r) and 2 nucleoside reverse transcriptase inhibitors (NRTls). This review will focus on the data of the drug-drug interactions between the PIs and rifampicin, with an emphasis on LPV/r.

Includes bibliographical references / South Africa has a very high rate of HIV infection, particularly among women. This exploratory study investigated the role of revictimization in the relationship between childhood sexual abuse and adult HIV positive status among women being treated at district clinics in Cape Town The present study utilized both psychological and feminist theories to understand internal psychological dynamics and contextual factors that impact on revictimization leading to increased HIV risk. A qualitative feminist methodology with a collective case study design utilizing five in-depth interviews was conducted with HIV positive women who had experienced child sexual abuse. The central findings of the study revealed psychological patterns of negative stigmatization, self-blame, mistrust and isolation which may fuel a dependent need for connection with intimate partners, thereby increasing risk for revictimization. Revictimization was pervasively present in adulthood, with HIV infection being a consequence of ongoing sexual and/or physical assault in long-term intimate relationship. Participants reported not using condoms consistently. For these participants, an incapacity to insist on condom use by partners was understood in the context of ongoing sexual and physical violence and threats by their partners, rather than unassertiveness as has been commonly noted. In essence, it was noted in this study that participants who experienced child sexual abuse were disempowered due to both psychological processes and broader social inequities which made them particularly vulnerable to contracting HIV. However, the findings are provisional due to the methodology utilized. Recommendations for future research and HIV prevention and policy are offered.

The vast majority of fatherhood studies in South Africa have generally focused on absent, non-resident and unmarried fathers. Therefore, there has been a lack of studies that specifically investigate fathering perceptions and experiences, particularly among Black African men who are present in their children's lives and share residence with them. This study sought answers on how Black co-resident men perceive and experience fatherhood, through uncovering the fathers' understanding of their children's primary needs and factors that influence their parenting practices. Understanding their involvement included exploring their responsibilities, depth of their engagement, as well as the frequency of accessibility to their children. This study used a qualitative design, and specifically the exploratory approach, through face-to-face semi-structured interviews to understand the ways in which men who share residence with their children make sense of fatherhood. The interviews were conducted with twelve (12) Black fathers, sharing residence with their partners and young children aged zero to seventeen (17) years in Cape Town. Probing questions were asked to identify the meaning and unique understanding of their parenting practices, as well as their perceptions about their children's primary needs. Lamb et al.'s (1985) fathering involvement theoretical framework was used to further identify how the participants characterise responsibility, engagement and accessibility in their involvement with their children. The findings of this study suggested that resident fathers are generally involved in their children's lives right from conception. However, their level of involvement was different based on their cultural, socio-economic, and social experiences. Most fathers in this study still struggled to adjust their behaviour around child-care activities, such as changing nappies. Furthermore, they still considered child-care activities as something that was the responsibility of the mother, and when they got involved, they regarded that as helping the mother. Finally, this study confirmed that co-resident fathers are involved, and willing to participate, but often chose the activities they preferred, such as playing with or entertaining their children rather than actual child-caring roles.