The management of HIV-associated tuberculosis (TB) is complicated by the pharmacokinetic interactions between rifampicin (RMP) and co-administered protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors. Rifabutin (RBT) is an alternative rifamycin, preferred in patients requiring PIs. Recent studies suggest the current recommended dose of RBT in combination with boosted lopinavir (LPV/r) is suboptimal and there are insufficient pharmacokinetic data evaluating the interaction between RBT coadministered with efavirenz (EFV) and nevirapine (NVP). Pharmacogenomic studies have shown that RMP concentrations are lower in patients from sub-Saharan Africa with polymorphisms of the SLCO1B1gene but there is currently no data on the pharmacogenetic determinants of RBT exposure. The pharmacokinetics of RBT were evaluated at two different doses in HIV co-infected patients before and after the introduction of LPV/r, EFV and NVPbased antiretroviral therapy (ART). After six weeks of standard TB therapy, RBT 300 mg daily was started for four weeks. Thereafter patients were randomized to receive either RBT 150 mg daily or RBT 150 mg three times a week (TPW) with LPV/r, RBT 300mg or 450mg with NVP or RBT- 450mg or 600mg with efavirenz. After four weeks on the first RBT dose, patients switched to the alternate dose and continued until the end of TB treatment. Serial RBT and 25-O-desacetylrifabutin (dRBT) concentrations were measured during a dose interval before patients switched RBT doses. The median AUC0-24 and Cmax, of RBT in patients taking 150mg RBT TPW was significantly reduced when compared to the other treatment arms. 86% of patients whilst on this intermittent RBT arm had an AUC0-24 < 4.5 μg.h/mL, level that has been associated with acquired rifamycin resistance. Rifabutin exposure was maintained within the range of AUCs that have been shown to prevent acquired rifamycin resistance (ARR) with 150mg daily dosing in combination with LPV/r. In addition, the combination of RBT with NVP 300mg resulted in significantly increased exposure of RBT, with significantly higher exposure observed with 600mg RBT. However, the combination of RBT 450mg with EFV resulted in RBT exposure lower than 300mg RBT given alone in the same patients, whereas RBT 600mg plus NVP results in bioavailability of RBT equivalent to 300mg given alone. Rifabutin was well tolerated at all doses. Only three grade 4 laboratory toxicities, elevated transaminases, neutropenia, and uveitis, possibly related to RBT were reported in patients taking NVP. SLCO1B1 rs4149032 C>T polymorphism occurs frequently in African patients in Durban and may be associated with low RBT bioavailability. These findings support recommendations for the higher dose of RBT in combination with LPV and EFV but not with NVP. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

Relationships between the steroid hormones estradiol (E2), testosterone (T), cortisol (CRT) and dehydroepiandrosterone-sulfate (DHEAS), memory and mood were investigated in men, in women estrogen-users and non-users, and in patients with Alzheimer's Disease (AD). In Study 1, 72 year-old healthy men and women estrogen-users performed better than estrogen non-users on Forward and Total Digit Span, which test attention and short-term memory, concomitant with their higher E2 levels. The estrogen-users performed better than the men and the non-users on Delayed Selective Reminding, a test of explicit verbal memory. Men and women with higher CRT levels performed worse on several explicit verbal memory tests compared to those with lower endogenous, CRT levels. In Study 2, male patients with AD performed better than estrogen non-using women with AD on several everyday memory tests, and women estrogen-users with AD performed similarly to the men. Both the men and estrogen-users had higher levels of E2 than the non-users. AD patients with higher endogenous levels of DHEAS performed better than those with lower levels on several everyday memory tests, and AD patients with higher CRT levels were impaired on one aspect of everyday spatial memory, Route Recall. In Study 3, no differences in hormone levels between AD patients and age-matched healthy elderly controls were found. The AD patients were most severely impaired on tasks involving explicit verbal recall compared to healthy controls, and least impaired on short-term memory and concentration tasks. The AD patients reported more dysphoric mood and mental dulling symptoms than healthy age-matched controls, but they did not report feeling less positive about the future. Taken together, these results suggest that higher levels of DHEAS and E2 are related to better memory performance in both healthy elderly men and women and in patients with AD, and higher CRT levels are associated with poorer explicit verbal memory performanc

Previous research indicates that young adults (aged 18-30) tend to exhibit a negativity bias such that they enhance processing of negative emotional stimuli compared to neutral stimuli. Because of age-differences in emotion regulatory goals, older adults (aged 60+) often exhibit enhanced processing for positive rather than for negative stimuli a positivity effect. I examined age-related differences in processing emotional facial expressions using event-related potentials (ERPs) elicited by task-relevant emotional (i.e., angry, sad, happy) and neutral face images and concurrent task-irrelevant central and peripheral probes. The results indicate that young and older have similarities and differences in their processing of emotional expressions. Both groups exhibit enhanced processing of all emotional facial expressions. This suggests that there is neither a negativity bias nor positivity effect in processing task-relevant emotional facial expressions. Instead, both young and older adults enhance processing of all emotional expressions compared to neutral expressions and therefore exhibit an emotional bias. Young and older adults differ in how the emotional faces affect processing of concurrent stimuli. Emotion enhanced processing of concurrent stimuli presented in other areas of the visual field only for the young adults.

Older adults inadvertently plagiarize more than young adults (McCabe, Smith, & Parks, 2007). One current explanation proposes that this effect can be understood in terms of age-related declines in working and episodic memory (McCabe et al., 2007). The current study tested this hypothesis by placing groups of young and older adult participants under divided attention while performing within the typical experimental paradigm. Results indicated that for some measures, dividing the attention of young adults equated their performance to older adults with full attention. For other measures, older adults still produced more errors. Except for false recall, regression analyses revealed that episodic and working memory accounted for age-related variance in these plagiarism errors. The current findings provide tenuous support for the McCabe et al. (2007) hypothesis and suggest other factors may be at play.

The research presented here focused primarily on an attempt to bridge the two literatures of source memory and metameory on the topic of 'monitoring'. The contributions were two-fold: an investigation of the viability of a metacognitive judgment for SM: the judgment of source learning (JOSL), and a simultaneous investigation of the relationship of age and 'monitoring' in source memory and metacognition. In the first experiment, young participants (18-25 years of age) were asked to predict (using JOSLs) whether they would be able to discriminate between pictures that were presented to them during study, images of words they generated during study, or words they never studied in a later memory test. Participants made either immediate or delayed JOSLs (on a 0-100 scale) for each item presented during the study phase. Experiment 2 was a cross-sectional study comparing young and old adults (60-80 years of age) using a modified version of the previous task. In both experiments, intraindividual correlations of JOSLs with SM (gammas) indicated that delayed JOSLs were accurate predictors of future SM performance. There were no effects of age on gamma correlations of JOSLs with SM. Based on these results, although SM showed an age-related deficit, metacognitive predictions of SM did not show this same effect.

Social ideologies appeared to influence dietary behaviour, physical activity and BMI. These influences varied through different pathways in younger and older baby boomers. Studies provide insight into the segmentation of baby boomer population in relation to concrete social ideologies that could be used for policy development and effective health promotion.

[Truncated abstract] The aim of the present series of studies was to identify barriers to working memory for multifeature visuospatial stimuli in normal aging. Memory for multifeature stimuli requires retention of multiple visuospatial features, as well as the relationships between features within stimuli, known as memory binding. In Experiment 1, younger people (17-25 years) and older people (66-95 years) completed a modification of Wheeler and Treisman’s (2002) visual change detection task, to determine the effects of normal aging on memory binding, and memory for multiple features ... Results indicated that older people did not have a memory binding decrement compared to younger people. Further, younger people performed more accurately when cued to attend to a specific feature, while older people’s performance did not improve with cueing ... Experiment 2 employed the binding condition and the ‘either’ condition, with stimuli presented either sequentially or simultaneously. Results were consistent with Experiment 1, with no age-related binding decrement, regardless of the method of stimulus presentation. In Experiment 1, older people demonstrated a shape memory decrement compared to younger people. Experiments 3A and 3B were performed to determine whether this result did represent a memory decrement per se, or whether it was a consequence of a shape perception decrement ... Compared to younger people, older people demonstrated a similar performance decrement across shape perception and memory tasks, indicating that their performance was mediated by an underlying perceptual decrement. Experiment 4 was conducted to determine if older people had difficulty selectively attending to a feature across multifeature stimuli, as suggested by their failure to benefit from cueing in Experiment 1 ... Older people had a greater performance decrement when the irrelevant feature was incompatible with the correct response, compared to younger people, consistent with a selective attention decrement. Experiment 5B adapted the design of Experiment 4 to both a perception task and a working memory task, while Experiment 5A identified appropriate stimulus features to use in Experiment 5B ... Overall, older people do not have particular difficulty remembering multiple visuospatial features, or binding these features within working memory. Rather, older people’s performance was marked by difficulty selectively attending to a specified feature across multifeature stimuli.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [111]-128).

Thesis (Ph.D.)--University of Melbourne, Centre for Neuroscience and Howard Florey Institute, 2009. / Typescript. Includes bibliographical references.