An exploration of sociodemographic and psychosocial determinants of cognitive performance in a peri-urban clinic population of people with HIV in Cape Town, South Africa

Introduction. Numerous studies, conducted in many different countries, report that cognitive impairment is highly prevalent in people with HIV (PWH). Such impairment can affect adherence to antiretroviral therapy (ART), and adherence is, in turn, essential for PWH to achieve viral suppression. The gold standard to confirm cognitive impairment is a neuropsychological assessment. However, accurate interpretation of neuropsychological test performance requires consideration of, for instance, how impairment is determined and how accurately the contribution of non-HIV factors to poor cognitive test performance is described. These non-HIV factors include sociodemographic variables (e.g., age, sex, educational attainment), psychosocial variables (e.g., socioeconomic status, food security, quality of life), psychiatric variables (e.g., depression, problematic alcohol use), and other medical co-morbidities. Because many existing studies of PWH do not account for (a) the fact that current quantitative methods for defining cognitive impairment may not accurately reflect HIV-associated brain injury, and (b) possible contributions of non-HIV factors to cognitive test performance, it is possible that the reported prevalence rates of cognitive impairment in PWH are inaccurate (or, at least, do not solely reflect the contributions of HIV disease to the impairment). Another uncertainty in the HIV neuropsychology literature concerns sex differences in the cognitive performance of PWH. Some recent studies suggest that women with HIV (WWH) may present with greater cognitive impairment than men with HIV (MWH). Such a sex difference is of potentially significant concern for South African clinicians because two-thirds of the population of PWH in this country are women. However, there is no definitive empirical evidence regarding whether this sex difference exists to a clinically significant degree (in South Africa, specifically, as well as globally) and what its underlying mechanisms might be. To address the knowledge gaps outlined above, this thesis set out to explore the following aims: (1) investigate sex differences in the cognitive performance of PWH by reviewing the current published literature; (2) determine if sex differences exist in a clinic sample of South African PWH; (3) determine how much variation in reported prevalence rates of HIV-associated cognitive impairment are due to the method used to define impairment, and which method correlates best with MRI biomarkers of HIVrelated brain injury in a South African sample of PWH; (4) investigate the contribution of sociodemographic and psychosocial variables, as well as HIV-disease factors and other medical and psychiatric comorbidities, to cognitive performance in a South African sample of PWH; and (5) investigate associations between cognitive performance and ART adherence in 10 a South African sample of PWH. Each of these aims was explored in a separate study. Hence, this thesis reports on findings from five separate journal manuscripts. Method. Study 1 was a systematic review and meta-analysis summarizing the findings of published studies investigating differences in cognitive performance between WWH and MWH. An extensive systematic search of the literature across several databases found 4062 unique articles of potential interest. After thorough screening of that pool of articles, 11 studies (total N = 3333) were included in the narrative systematic review and 6 studies (total N = 2852) were included in the meta-analysis. Effect sizes were calculated to estimate between-sex differences in cognitive performance, both globally and within discrete cognitive domains. Study 2 investigated sex differences in cognitive performance in a sample of PWH with comorbid MDD (N = 105). All participants were attending community clinics in Khayelitsha, a peri-urban community in Cape Town, South Africa, and were part of a larger research program for a randomised controlled trial of a cognitive-behavioral treatment for ART adherence and depression (CBT-AD). As part of this program, they completed baseline neuropsychological, psychiatric, and sociodemographic assessments. T-tests and multivariable regressions controlling for covariates compared baseline cognitive performance of WWH and MWH, both globally and within discrete cognitive domains. Study 3 applied 20 different quantitative methods of determining cognitive impairment to existing data from a different sample of PWH (N = 148). These individuals had also been recruited from community clinics in Khayelitsha, and had completed a comprehensive neuropsychological assessment and a 3T structural MRI and diffusion tensor imaging (DTI) session. Logistic regression models investigated the association between each method and HIV-related neuroimaging abnormalities. Study 4 again used data from the sample of PWH with comorbid MDD who participated in the larger CBT-AD research program. This study investigated which sociodemographic, psychosocial, psychiatric, and medical variables (as measured at baseline) were associated with baseline cognitive performance. Post-baseline, 33 participants were assigned to CBT-AD and 72 to standard-of-care treatment; 81 participants (nCBT-AD = 29) had a follow-up assessment 8 months post-baseline. This study also investigated whether, from baseline to follow-up, depression and cognitive performance improved significantly more in the participants who had received CBT-AD, and examined associations between post-intervention improvements in depression and cognitive performance. Study 5 assessed ART adherence in the same sample of PWH with comorbid MDD. Mixed-effects regression models estimated the relationship between ART adherence (as measured by both self-report and objective measures, and by degree of HIV viral suppression) with cognitive performance 11 and with other sociodemographic, psychosocial, and psychiatric variables at both baseline and follow-up. Results. Study 1: Analyses suggested that, in terms of overall cognitive functioning, there were no significant differences in cognitive performance between WWH and MWH. However, WWH did perform significantly more poorly than MWH in the domains of psychomotor coordination and visuospatial learning and memory. Additionally, the review suggested that cognitive differences between WWH and MWH might be accounted for by sex-based variation in educational and psychiatric characteristics among study samples. Study 2: Analyses suggested that, in our sample of PWH with comorbid MDD, there were no significant differences in cognitive performance between WWH and MWH. Study 3: Findings suggested that there was marked variation in rates of cognitive impairment (20– 97%) depending on which method was used to define impairment, and that none of these methods accurately reflected HIV-associated brain injury. Study 4: Analyses suggested that less education and greater food insecurity were the strongest predictors of global cognitive performance. Improvement in depression severity was not significantly associated with improved cognitive performance, except in the domain of Attention/Working Memory. Overall, factors associated with cognitive performance were unrelated to HIV disease and other medical factors. Study 5: Analyses identified poor global cognitive performance as a potential barrier to achieving HIV suppression. Conclusion. Taken together, the findings from the five studies contained within this thesis suggest that one oft-mooted sociodemographic influence on cognitive performance in PWH, sex, was not a consistent influence on such performance. However, non-biological (mainly psychosocial and socioeconomic) factors were stronger predictors of cognitive performance in PWH than medical factors (including HIV-disease variables). Current quantitative criteria for defining cognitive impairment in PWH also do not accurately reflect the biological effects of HIV in the brain. The implication of these findings is that research studies may be misclassifying PWH as cognitively impaired and consequently overestimating the prevalence of cognitive impairment in this population. When conducting clinical assessments of PWH, future research studies should measure and consider the strong influence of psychosocial and socioeconomic factors on cognitive test performance. Ideally, a diagnosis of impairment should only be made after a comprehensive clinical assessment that includes a detailed history taking. Overall, we need new criteria for defining cognitive impairment in diverse global populations of PWH. Ideally these criteria should be applicable to both research and clinical settings. Assessing for cognitive impairment among PWH and then providing 12 appropriate support could help achieve viral suppression in patients with non-optimal adherence to ART. At public policy levels, addressing larger psychosocial issues (e.g., food insecurity and low educational attainment) may also help improve cognitive performance in PWH

A multicomponent intervention to optimise nurseepatient communication in the intensive care unit: A mixed-methods acceptability and feasibility study

Background Mechanically ventilated patients in intensive care units may experience communication challenges owing to intubation, which affects nurse–patient communication. Several strategies may optimise communication, but only one previous study has tested a multicomponent intervention. Implementing such an intervention can be challenging because communication strategies may be set aside by lifesaving care tasks and procedures. In a previous study, we designed a communication intervention based on pre-existing clinical methods and evidence-based approaches. The present study evaluated the intervention to determine if it was necessary to adjust its components and the implementation strategy. Objectives The objective of this study was to evaluate the feasibility and assess nurses’ acceptability of a patient-centred, multicomponent communication intervention prototype in an intensive care unit. Methods The overall frame was the Medical Research Council's framework for developing complex interventions. Indicators of feasibility and acceptability were used for the evaluation. A mixed-methods design was applied including a survey with open-ended text boxes and qualitative observations as data sources. Quantitative data were analysed descriptively, and qualitative data were explored using content analysis. Data were compiled and displayed in a side-by-side comparison. The data were collected between September 2020 and March 2021. Nurses from four intensive care units at a university hospital in Denmark participated in the study. All nurses who were on active duty during the implementation of the intervention were enrolled for the survey and participant observations. Results Overall, the results provided insight into the feasibility based on fidelity and context as well as nurses’ acceptability based on adherence, appropriateness, convenience, and effectiveness. Qualitative and quantitative results yielded partially contrasting findings but highlighted how the intervention may be optimised to enhance fit with clinical practice and overcome implementation challenges. Conclusion The intervention was feasible and acceptable. However, implementation needs to be repeated to allow nurses to fully understand and use the intervention.publishedVersio

Prevalence and diversity of Chlamydiales in Swiss ruminant farms

Chlamydia and Chlamydia-related bacteria are known to infect various organisms and may cause a wide range of diseases, especially in ruminants. To gain insight into the prevalence of these bacteria in the ruminant environment, we applied a pan-Chlamydiales PCR followed by sequencing to 72 ruminant environmental samples from water, feed bunks and floors. Chlamydiales from four family-level lineages were detected indicating a high biodiversity of Chlamydiales in ruminant farms. Parachlamydiaceae were detected in all three types of environmental samples and was the most abundant family-level taxon (60%). In contrast, only one bacterium from each of the following family-level lineages was identified: Chlamydiaceae, Criblamydiaceae and Simkaniaceae. The observed high prevalence of Parachlamydiaceae in water samples may suggest water as the main source of contamination for ruminants as well as their environment due to spoilage. The absence of reported infections in the investigated ruminant farms might indicate that either detected Chlamydiales are of reduced pathogenicity or infective doses have not been reache

Strengthening and supporting nurses’ communication with mechanically ventilated patients in the intensive care unit: Development of a communication intervention

Background Nurse-patient communication in intensive care units is challenged by the fact that patients are voiceless due to intubation and mechanical ventilation. Difficult communication affects nurses negatively, and it requires knowledge and expertise to facilitate communication in this complex and technologically tense setting. Augmentative and alternative communication has been suggested as a way of optimising communication; several approaches can be combined in a multi-component intervention. Also, a communication algorithm has been proposed as a way of providing structure in patient communication. To enhance transparency and avoid poorly reported interventions, this paper describes the process, rationale and reflections behind developing a communication intervention called the ICU-COM. Objectives To present the development process of a communication intervention prototype that aims to support and strengthen nurses’ communication with mechanically ventilated patients in an intensive care unit. Design The Medical Research Council's framework for developing complex interventions in health was applied. The approach was target-population centred. Settings The intervention was developed and tailored to four intensive care unit departments at Aarhus University Hospital in Denmark. Participants Intensive care nurses and various experts, namely, speech-language pathologists, graphic designers, a software company, the local Centre for E-learning and nurse specialists were involved in its development. Results An intervention consisting of: 1) a multi-component communication bundle, 2) delivery of the bundle via a teaching session and 3) initial implementation via nurse communication guides was developed. The communication bundle contained: 1) a communication strategy with a BASIS framework and algorithm, 2) a nurse education programme and 3) low-tech and high-tech communication tools. Conclusions A systematic approach was applied in the development process. However, the acceptability and feasibility of the intervention is at present unknown.publishedVersio

Likelihood and Bayesian signal processing methods for the analysis of auditory neural and behavioral data

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references.Developing a consensus on how to model neural and behavioral responses and to quantify important response properties is a challenging signal processing problem because models do not always adequately capture the data and different methods often yield different estimates of the same response property. The threshold, the first stimulus level for which a difference between baseline activity and stimulus-driven activity exists, is an example of such a response property for both neural and behavioral responses.In the first and second sections of this work, we show how the state-space model framework can be used to represent neural and behavioral responses to auditory stimuli with a high degree of model goodness-of-fit. In the first section, we use likelihood methods to develop a state-space generalized linear model and estimate maximum likelihood parameters for neural data. In the second section, we develop the alternative Bayesian state-space model for behavioral data. Based on the estimated joint density, we then illustrate how important response properties, such as the neural and behavioral threshold, can be estimated, leading to lower threshold estimates than current methods by at least 2 dB. Our methods provide greater sensitivity, obviation of the hypothesis testing framework, and a more accurate description of the data.Formulating appropriate models to describe neural data in response to natural sound stimulation is another problem that currently represents a challenge. In the third section of the thesis, we develop a generalized linear model for responses to natural sound stimuli and estimate maximum likelihood parameters. Our methodology has the advantage of describing neural responses as point processes, capturing aspects of the stimulus response such as past spiking history and estimating the contributions of the various response covariates, resulting in a high degree of model goodness-of-fit.(cont) Using our model parameter estimates, we illustrate that decoding of the natural sound stimulus in our model framework produces neural discrimination performance on par with behavioral data.These findings have important implications for developing theoretically-sound and practical definitions of the neural response properties, for understanding information transmission within the auditory system and for design of auditory prostheses.by Anna A. Dreyer.Ph.D

Predicting lateralization performance at high frequencies from auditory-nerve spike timing

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (leaves 77-82).Psychophysical sensitivity to interaural time differences (ITD) in the envelope of high- frequency sinusoidally amplitude-modulated (SAM) tones is generally poorer than that to low- frequency pure tones (PT). ITD sensitivity at high frequencies might be improved using "transposed stimuli" (TS), which seek to produce the same temporal discharge patters in high- frequency neurons as in low-frequency neurons for PT. Here, we study ITD sensitivity for PT, SAM tones and TS using neurophysiology, psychoacoustics and computational models. Phase locking of auditory-nerve fibers in anesthetized cats was characterized using both the synchronization index and autocorrelograms. With both measures, phase locking is stronger for PT than TS, and for TS than for SAM tones. Phase locking to SAM tones and TS degrades with increasing stimulus level, while remaining more stable for PT. ITD discrimination was measured in humans for stimuli presented either in quiet or with band-reject noise intended to restrict listening to a narrow frequency band. Performance improves slightly with increasing stimulus level for all three stimuli both with and without noise. ITD sensitivity to TS is comparable to PT performance only in the absence of noise. To relate psychophysical performance to auditory-nerve activity, we developed a physiologically-based optimal binaural processor model with delay lines and coincidence detectors. In the no-noise condition, model performance is stable with stimulus level, consistent with psychophysics. However, in the band- reject noise condition, model performance for SAM tones and TS degrades with increasing level. .(cont.) These results have implications for the relative roles of peripheral patterns of activity and the binaural processor in accounting for ITD sensitivity at low versus high frequenciesby Anna Alexandra Dreyer.M.Eng

The Christ narrative in the film As it is in heaven

The Christ narrative in the film As it is in heaven. In this article the public-theological motives in the film As it is in heaven is analised to demonstrate the film producer Kay Pollack’s ideal to communicate through the film that people should live their lives here and now authentically without seeking excuses for being happy. In this article the principles of narratology is applied in the analysis of the film’s plot, characterisation, plotted time and narrated spaces. It is also argued that the protagonist in the film can be regarded as a ‘Christ-figure’ and that the film conveys a ‘Christ narrative’ in a secularised context. Societal issues such as emotional abuse and violence against children, women, people with disability and animals constitute building blocks of the narrative. Ecclesiastical hypocrisy and outdated sexual values endorsed by the institutional church are replaced by a choir consisting of common people which leads a whole world to sing in harmony.This article is based on the research of Anet Dreyer- Kruger’s PhD dissertation, entitled ‘Filmhermeneutiek: Die huwelik, intimiteit, seksualiteit en die Christusnarratief’.http://www.hts.org.zatm201

Function and Regulation of Chloroplast Peroxiredoxin IIE

Peroxiredoxins (PRX) are thiol peroxidases that are highly conserved throughout all biological kingdoms. Increasing evidence suggests that their high reactivity toward peroxides has a function not only in antioxidant defense but in particular in redox regulation of the cell. Peroxiredoxin IIE (PRX-IIE) is one of three PRX types found in plastids and has previously been linked to pathogen defense and protection from protein nitration. However, its posttranslational regulation and its function in the chloroplast protein network remained to be explored. Using recombinant protein, it was shown that the peroxidatic Cys121 is subjected to multiple posttranslational modifications, namely disulfide formation, S-nitrosation, S-glutathionylation, and hyperoxidation. Slightly oxidized glutathione fostered S-glutathionylation and inhibited activity in vitro. Immobilized recombinant PRX-IIE allowed trapping and subsequent identification of interaction partners by mass spectrometry. Interaction with the 14-3-3 υ protein was confirmed in vitro and was shown to be stimulated under oxidizing conditions. Interactions did not depend on phosphorylation as revealed by testing phospho-mimicry variants of PRX-IIE. Based on these data it is proposed that 14-3-3υ guides PRX‑IIE to certain target proteins, possibly for redox regulation. These findings together with the other identified potential interaction partners of type II PRXs localized to plastids, mitochondria, and cytosol provide a new perspective on the redox regulatory network of the cell