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Heteroleptic dirhodium (II,II) complexes: synthesis, spectroscopy and applications in hydroformylation and hydroaminomethylation catalytic reactions
Get PDFThe synthesis of a series of bis-substituted heteroleptic dirhodium(II,II) complexes containing bridging acetate and chelating bipyridyl ligands is herein described. The protons at the 4- and 4'- positions of the bipyridyl ligands on the model complex 1 were substituted by either the electron withdrawing CF3 (complex 2) or electron donating OMe (complex 3) groups, to observe the electronic influence on the metal complexes. As such, electroanalysis using cyclic voltammetry indicated variations in the metal-centred redox processes for the title complexes. The complexes obtained were used as pre-catalysts for the hydroformylation and hydroaminomethylation of olefins, an unprecedented homogenous catalysis system
An investigation of amygdala and hippocampal subregions and their relation to ageing in anxiety and related disorders
Get PDFBackground Obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD) are debilitating disorders that are associated with (inconsistent) evidence of hippocampal and amygdala volumetric abnormalities. In addition, both OCD and SAD are associated with accentuated biological aging, as indexed by cellular and molecular markers. Nevertheless, little is known about brain aging in OCD and SAD, or the extent to which inconsistencies in hippocampal and amygdala volume findings in these disorders may be due to the differential effect of age on the subfields from which these structures are composed. Accordingly, this dissertation set out to characterise differences in hippocampal and amygdala subfield volumes between healthy controls (HCs) and participants with OCD and SAD in large-scale MRI datasets and relate these to whole and regional brain aging. Methods Hippocampal and amygdala subfield volumes and brain age estimates were derived from T1 weighted MRI images from the OCD Brain Imaging Consortium (De Wit et al., 2014) and the European and South African Research Network in Anxiety Disorders (Bas-Hoogendam et al., 2017). Subfield volumes were segmented using an automated segmentation algorithm from Freesurfer (v6.0). The brain age analysis was performed by using a previously trained machine learning algorithm that provides brain age estimates for the whole brain, as well as for regions of interest (occipital, frontal, temporal, parietal, cingulate, insula, or cerebellar–subcortical features) (Kaufmann et al., 2019). Differences in relative brain age (brain predicted age difference; brain-PAD) were calculated by subtracting chronological age from the predicted brain age. Between-group differences (diagnosis vs HCs) in volumetric and brain-PAD estimates were assessed using a mixed-effects (d) model adjusted for several covariates. Subgroup analyses were performed to determine the association of the main findings with clinical characteristics. Finally, unique associations between subfield volumes and whole brain age were estimated using partial correlation analysis. Results There was no evidence for a difference in subfield volumes between individuals with OCD and HCs. However, we found that psychotropic medication use was associated with significantly smaller hippocampal dentate gyrus (d=-0.26, pFDR=0.042), molecular layer (d=-0.29, pFDR=0.042) and larger lateral (d=0.23, pFDR=0.049) and basal (d=0.25, pFDR=0.049) amygdala subfields than HCs. Individuals with OCD without psychotropic medication use had significantly smaller hippocampal CA1 (d=-0.28, pFDR=0.016) compared to HCs. No association was found for symptom severity. In contrast to the findings for OCD, individuals with SAD demonstrated significantly smaller basal (d= 0.32, pFDR=0.022), accessory basal (d=-0.42, pFDR=0.005) and corticoamygdaloid transition area (d=0.37, pFDR=0.014) amygdala subfields overall compared to HCs, and larger hippocampal CA3 (d=0.34, pFDR=0.024), CA4 (d=0.44, pFDR= 0.007), dentate gyrus (d=0.35, pFDR= 0.022) and molecular layer (d=0.28, pFDR=0.033). In addition, individuals with SAD without comorbid anxiety disorder had smaller lateral amygdala and hippocampal amygdala transition area, compared to HCs. No association was found for psychotropic medication use and symptom severity. Individuals with OCD (n=375) had significantly higher whole brain-PAD (+1.6 years, pFDR=0.006, d=0.20) compared to HCs (n=335), but no differences were observed in the regional models. The effect on whole brain brain-PAD estimates was largely driven by psychotropic medication use as higher relative brain age was evident in individuals with OCD with psychotropic medication use (+2.98 years, d=0.38, p <0.001) compared to HCs, but not in individuals without psychotropic medication use (+0.57 years, d=0.07, p =0.374) compared to HCs. No association was found for symptom severity. Partial correlation analysis found a significant negative association between hippocampal and amygdala volume and whole brain PAD in the OCD group (R=-0.224, p=0.00001), but not in the HC group (R=0.081, p=0.138), specifically the lateral nucleus (R=-0.18), CAT(R=-0.13), hippocampal fimbria (R=0.17), and hippocampal fissure (R=0.17) were significant in OCD. Individuals with SAD (n=107) had significantly higher whole brain-PAD (+2.5 years, d=0.33, pFDR=0.010) compared to HCs (n=137), and significantly higher regional brain-PAD in the temporal (+3.80 years, d=0.37, pFDR=0.008,), parietal (+3.57 years, d=0.38, pFDR=0.008), occipital (+3.26 years, d = 0.33, pFDR=0.010), and frontal regions (+2.97 years, d=0.33, pFDR=0.010,) compared to HCs. Brain PAD was higher in SAD without comorbid anxiety disorder, without MDD, and without psychotropic medication use. No association was found for symptom severity. There was no partial correlation between subfields and brain age. Discussion & Conclusion The evidence presented in the thesis suggests that 1) differences in subfield volumes between OCD and HCs were influenced by psychotropic medication use, which is consistent with previous studies that suggest that psychotropic medication status is a strong confounder for subcortical brain volumes observed in OCD, 2) differences in subfield volumes between SAD and HCs were observed in the areas associated with sensory information processing and these differences were partially influenced by psychiatric comorbidity, 3) both OCD and SAD were associated with accentuated brain aging with differential patterns in the whole and regional brain, dependent on clinical characteristics, and 4) only OCD relative brain age was associated with subfield volumes. It is unclear whether our findings in OCD and SAD reflect an adaptive response or are a pre-existing risk factor to these disorders, or both. Future longitudinal analysis is required to investigate whether the observed differences in subfield volume and brain age remain over time
Preliminary evidence that prenatal maternal choline supplementation protects the white matter microstructure of infants born to heavy-drinking women
Get PDFPrenatal alcohol exposure (PAE) is the most widespread preventable cause of neurocognitive and neurodevelopmental disabilities worldwide, known collectively as fetal alcohol spectrum disorders. It has been shown in a small double-blind, randomized choline supplementation trial that prenatal maternal choline supplementation reduces PAE-related postnatal growth restrictions, cognitive deficits, and regional brain volume reductions in infants born to heavydrinking women. The impact of prenatal maternal choline supplementation on white matter (WM) microstructure – an area particularly vulnerable to PAE – has not been assessed. This project used diffusion tensor imaging (DTI) in 43 neonates born to heavy-drinking mothers enrolled in that choline supplementation trial to examine the effects of prenatal maternal choline supplementation on the microstructure of WM connecting select subcortical regions. Given that pre-myelination (at 30-40 weeks gestational age (GA)) and maturation of the axonal cytoskeleton are categorised by stable fractional anisotropy (FA), decreasing axial diffusivity (AD) and radial diffusivity (RD), we hypothesised that neonates with PAE whose mothers had received choline would demonstrate lower AD and RD than those in the placebo arm, and that lower AD and RD would be associated with better cognitive performance. T1-weighted structural magnetic resonance (sMR) and diffusion tensor (DT) imaging (DTI) data were acquired for each neonate between 1-7 weeks postpartum on a 3T Siemens Allegra. Previously, 17 subcortical brain regions (ROIs) had been manually traced on sMR images in Freeview. After DTI pre-processing, the manually traced ROIs were transformed into the DTI space and used as seeds for full probabilistic tractography. FA, AD and RD were extracted for each identified connection. Visual recognition memory scores on the Fagen test of Infant Intelligence (FTII) assessed at 12 months were also available for 34 participants. We examined differences in the DTI measures between the choline and placebo groups, as well as associations of DTI measures with choline dose and FTII scores using robust linear regression. Choline dose was approximated in 2 ways: (1) using maternal treatment adherence (in % packets consumed), with choline dose set to zero for infants in the placebo arm, and (2) computing the total choline (in grams) consumed by the mothers throughout participation in the study (enrolment through to delivery). A total of 22 neonates (14 choline; 11 boys; mean GA (SD) = 41.8 (2.0) weeks) provided usable, non-biased DTI data and FTII scores were available for 14 of these neonates (8 choline). We examined treatment effects in 15 WM connections that were present in a least 85 % of the neonates. Three neonates in the choline arm whose mothers had low treatment adherence ( 0.40; p's < 0.05). Finally, better visual recognition memory on the FTII was associated with lower RD (β (ε) = -0.62 (0.27); p = 0.038) in the connection between the left and right thalami, and with higher RD (β (ε) = 0.54 (0.18); p = 0.009) in the WM connection between the right caudate and right putamen. Although choline-related decreases in FA were observed in the connection between the right caudate and right pallidum, the choline-related decreases in AD in the caudate, putamen and pallidum on the right aligned with our hypothesis. Studies of participants with Williams syndrome and attention-deficit/hyperactivity disorder have speculated that the lower FA observed in their control groups may be accredited to higher levels of axonal branching. Given that choline promotes axonal growth and branching in rodent models, the lower FA observed here may be indicative of choline-related increases in axonal branching in the caudate to pallidum connections. Studies of postnatal WM development have found that AD and RD decrease during the first postnatal year. Given that AD provides information on axonal integrity and organization, the age-related decreases for AD have been accredited to increases in axonal growth. Human studies have demonstrated increases in fibre cross-sections in the first 6 months of life and animal studies have shown the importance of choline in axonal growth and elongation. Thus, the choline-related reductions in AD in connections between the caudate, putamen and pallidum on the right suggest accelerated brain development through the promotion of axonal growth in these WM connections. Axonal pruning may also contribute to decreases in AD. Growth-related increases in axonal diameter may explain the association of higher RD seen in the same connection, right caudate to right putamen, with better visual recognition memory. The negative association between visual recognition memory and RD in the connection between the left and right thalami aligns with our hypothesis and several studies conducted in infants, children and adults. These results provide preliminary evidence that choline is associated with the microstructural properties of subcortical WM connections, specifically between the caudate, putamen and pallidum, which are regions known to be affected by PAE. These findings need to be replication in a larger sample and with unexposed controls. Further research is required to examine the impact of prenatal maternal choline supplementation on cortical WM
Investigating ecological drivers and impacts of vegetation change in sub Antarctic tundra
Get PDFUnderstanding the impact of environmental change on vegetation dynamics requires considering the individualistic responses of plant species, which are influenced by their specific habitat requirements and biotic interactions. For instance, habitat generalist species often have broad environmental tolerance, and may be able to adapt to and often dominate in dynamic or disturbed environments, compared to specialists that are adapted to specific environmental conditions and thus have more restricted tolerance to change. This study explores the potential for the combination of topographic, climatic, edaphic and biotic factors to influence different vascular plant species distributional and cover changes in response to the key drivers of change in the sub-Antarctic, focusing on Marion Island (MI). Given the recent origin and relative species poverty of the sub-Antarctic flora, changes in vegetation are expected to result from individual responses rather than collective trends across the entire flora or its communities. To evaluate the appropriate scale for vegetation assessment in species-poor environments, the classification of vegetation on MI was revisited. Various modern classification techniques were used to classify vascular plant species data, and the resulting classifications were compared with previous units. Due to the limited development of strong plant assemblages with discrete boundaries in the sub-Antarctic islands, community-level classification may not be suitable in such species-poor environments. Consequently, this study proposes a species-level approach aligned with continuum theory rather than community theory for more accurate vegetation monitoring in species-poor environments. Since the 1950s, MI has experienced changes in temperature, precipitation, wind conditions, and biotic interactions, with plant species thus experiencing altered environmental conditions. To investigate the vegetation cover changes across different habitats, repeat photography between 1965 and 2020 was used. Results showed an overall increase in vegetation cover in most habitats over the past five decades, accompanied by rapid drying, rising mean air temperature, changing wind direction, increased invasive plant species cover, and higher invasive house mouse abundance. Climate change and invasive species were identified as the primary interactive drivers of vegetation change. The increase in cover was primarily driven by more responsive species, such as habitat generalists, while habitat specialists either showed minimal changes or a decrease in cover. Since edaphic properties are an often overlooked component of habitat suitability or changes therein, the edaphic properties were modelled for the first time on MI to determine the spatial variation of key soil 4 properties across MI using boosted regression trees. The impact of temperature change on plant species distribution was then examined through species distribution models incorporating edaphic properties along with climatic, topographic and biotic factors. By considering a combination of climatic (changing), biotic, and non-climatic (fixed) predictors, the study aimed to determine the direction and constraints of species distributional changes under past and future temperature scenarios. Although the habitat requirements of vascular plant species on MI were species-specific, with species distributions predicted by differential variables, the responses of most generalist plant species to warming were similar, whereas responses of specialist species were similar. With continued warming, the habitat suitability of generalist plant species were predicted to increase on MI, within the physical constraints imposed by the environment, and toward the west, whereas the habitat suitability of most specialist species was not predicted to increase with warming. The results support the overarching hypothesis of this study that vegetation change on MI occurred as a consequence of the interaction of factors, key among them being climate change and invasive species. This research emphasises the individualistic responses of vascular plant species to environmental change in species-poor and/or young environments. Most habitat generalists have increased in cover and expanded their ranges, and these trends are projected to continue with warming, within the physical limitations of the environment. In contrast, the habitat suitability of specialist species show limited change, with no significant changes in cover observed or changes in range predicted with warming. Consequently, a comprehensive assessment of habitat suitability for different plant species requires considering a combination of topographic, climatic, edaphic, and biotic factors. This study highlights the importance of studying individualistic responses and understanding the specific habitat requirements of individual vascular plant species, which may be overlooked when focusing solely on species assemblage
Youth perceptions (18-24) on the role of youth clubs in delivering family planning information and services in Blantyre district, Malawi
Get PDFBackground: Unmet need for family planning is a significant health problem for youth in Malawi. In order to promote family planning uptake, youth clubs were established to provide a safe and friendly environment for the youth to access sexual and reproductive health information and services. Although these tailored youth clubs exist, evidence on family planning utilisation in this population has been collected in clinics and hospitals rather than youth clubs. This study explored the perspectives of the youth on the role of youth clubs in delivering family planning information and services including condom distribution. Methods: An exploratory qualitative study design was used for this study. Four focus group discussions and ten semi-structured interviews were used to collect information from young boys and girls aged between 18 – 24. Participants were purposively sampled and were asked to give a written consent before the commencement of the interviews. The discussions and semi-structured interviews were tape-recorded and transcribed verbatim. Transcripts were coded manually and analysed using thematic analysis. Results: Youth clubs played a role in creating awareness about family planning methods and promoting positive sexual and reproductive health wellbeing of young people. The youth identified effective facilitation skills, trained peer educators and dynamic collaborations with health service providers as the facilitators of smooth delivery of family planning information. The perceived barriers to the smooth delivery of family planning information in the clubs included limited availability of resources and religious/cultural biases. Conclusions: Youth clubs are crucial in empowering the youth with knowledge and understanding about family planning hence enabling them to make informed decisions about their sexual and reproductive health and wellbeing. Effective delivery of family planning information and services in youth clubs requires strong partnerships with relevant stakeholders such as local health service providers and non-governmental organisations through leveraging their expertise, resources and networks hence strengthening the impact of family planning initiatives
Jewish folksong: an ethnomusicological study of categories of Yiddish folksongs within the context of Jewish life in Eastern Europe, from the nineteenth century up to World War II, including partisan songs, and songs of the Holocaust and resistance
No full textThis study sets out to provide a cultural analysis of 56 Yiddish folksongs which are representative of some of the bestknown folksong styles among Ashkenazi Jews. Actual research was carried out over two years, mainly in Cape Town, with short visits abroad to the United Kingdom, and to Israel. The research procedure is based on Gerhard Kubik's 'integrated-study' approach. Accordingly, I approached my subject from several perspectives: historical, sociological, musicological, literary, and linguistic - and researched it on an emic basis. The research material was obtained from a number of sources - from oral information, literature, song collections and sound recordings, and from personal observation. The aim of this study is: (i) to identify intrinsic structural and stylistic features within Yiddish folksongs; (ii) to investigate significant traits concerning their performance practice in their original social contexts, and in presently 'controlled' contexts. The study design is as follows: there are two main parts, Part I and Part II. Part I comprises three chapters: ( i) Chapter 1 is an Introduction giving a historical and socio-cultural overview of Ashkenazi folksong, and the work of pioneer folksong investigators; Chapter 2 surveys historical and political factors which have been largely responsible for the great diversity of Jewish musical traditions, and delineates the various Jewish communities living in geographically defined areas today. The need for comparative studies spanning these different communities is stressed; Chapter 3 is concerned with the history of the Yiddish language, its emergence and development as a spoken language (with dialects), and as a literary language with a standardized orthography; (ii) Part II comprises two chapters: Chapter 1 explains the reasons for my adoption of certain research. procedures, and pays particular attention to the socio-cultural background and content of the songs, and their arrangement according to genre. Each song is handled as a distinct item, and transcriptions and texts of all the songs appear at, or near the end of, each genre description. Recorded performances of 27 of the 56 songs appear on a cassette tape which accompanies this study; their texts and music appear on yellow pages, to make for easy location. Chapter 2 concentrates on the purely musicological aspects of the songs. Particular attention is drawn to the way in which songs of 1 shtetl' (village/ small town) origin have been transformed to accommodate the necessities of their mass distribution. A Summary concludes this study, in which attention is also drawn to the 1 recreative 1 aspects of Yiddish folksongs, which persist despite the impact of the huge Jewish folklore industry, and the mass media. A plea is made for a synchronic 'context sensitive' approach to the study of CURRENT performances of Yiddish music, in different performance environments, along the lines advanced by ethnomusicologist Regula Burckhardt Qureshi (1987). This study contains a Preface, and a Glossary of Yiddish and Hebrew terminology, a Bibliography and a Discograph
What the f*ck just happened? : A study of the post-rape decision-making on safety, response and justice by adolescent girls in South Africa
Get PDFOne in every three South African teenagers has experienced sexual violence but how they respond to their victimisation remains a paradoxical yet pivotal question. Teenagers must decide whether to seek (in)formal support following being raped, which has implications for their protection, health, and well-being. However, the role of adolescent rape survivors as decision-makers remains under-investigated. Therefore, this study aims to understand the multifaceted factors that influence the decision-making on safety, response, and the pursuit of justice by teenage girls following sexual victimisation. Drawing from interviews with female teenage survivors of sexual violence (n=40), caregivers of survivors (n=11), key informants working in the field of sexual violence (n=16), and adolescent peer educators (n=18), my primary research question examines the underlying ‘how' and ‘why' of the post-victimisation decision-making on safety, response, and justice by South African teenagers; and how Bourdieu's theoretical concepts of habitus, capital, field, and practice offer a novel framing for understanding their decision-making following sexual victimisation. Through the lens of Bourdieu's ‘Theory of Practice', I foreground the adolescent decision-maker and show that the context in which experiences are gained, tendencies are developed, and resources are acquired matters for how they respond to rape. The findings suggest that the teenagers' decisions are not made in a vacuum, isolated from the violence happening all the time, all around them. Growing up in some of South Africa's most violent and marginalised communities, they learn how to navigate crime, recognise sexual violence, seek safety, and cope with deficiencies in resources, which becomes the foundation for their decision-making following being raped. I argue that responding to dangerous situations has become a routinised practice for the young women, and that understanding their post-rape decisions requires paying attention to their everyday reality as a source of routine, socialising experiences, available support and monetary resources, sources of information, and recourseseeking options within their communities. None of these experiences and conditions alone sufficiently explains the decision-making, but it is the interplay between learning, support, information, resources, and safety provisions and response that explains how and why teens respond to their sexual victimisatio
Characterising vaginal Lactobacillus strains from young South African women with persistently optimal vaginal microbiota – Developing the framework for an African vaginal probiotic product development platform for reproductive health
Get PDFBackground: Bacterial vaginosis (BV) is a genital condition with a high prevalence in sub-Saharan Africa, which can cause adverse sexual and reproductive health outcomes. Treatment with antibiotics such as metronidazole results in only a brief resolution of the vaginal dysbiosis present in BV and the recurrence rates are high. Probiotics have been explored as a possible adjunctive treatment option, but most commercially available formulations do not contain vaginally-derived strains and there is limited evidence for their efficacy in local populations. Therefore, there is an urgent need for the development of vaginal probiotics tailored towards sub-Saharan African women containing strains with useful probiotic characteristics that have the potential to persistently colonise the female genital tract. Aim: This project aimed to isolate and characterise Lactobacillus strains from young South African women with a stable optimal vaginal microbiota for consideration as candidate strains in a vaginal probiotic product. Methods: Samples from a previously completed study cohort where hormonal contraceptive preferences were examined in adolescent and young women in Cape Town (UChoose) were used for this study. Samples were collected from healthy, HIV uninfected young women (aged 15-19) at three timepoints, 16 weeks apart. To identify women with a stable and optimal vaginal microbiota over time, vaginal microbial communities were classified using VALENCIA. Lactobacillus spp. were selectively isolated from participants with longitudinally stable Lactobacillus crispatus- dominant communities and assayed for their ability to inhibit Prevotella bivia, a BV-associated organism using a soft agar overlay method. Candidates with strong inhibition potential against P. bivia were characterised further fortheir inhibition potential against regionally relevant BV-associated organismsisolated from women within the same study cohort, as well astheir growth at physiologically relevant pH (pH 4, 4.5 and 5), their ability to produce lactic acid and finally their resistance to commonly used BV and urinary tract infection antibiotics. Additionally, whole genome sequencing (WGS) data were available for three strains and these were assessed to determine additional safety characteristics of the probiotic candidates. The strains were screened for antimicrobial resistance genes using several online databases (ResFinder, ARG-ANNOT, CARD, NCBI AMRFinderPlus and VFDB), the presence of integrated prophages using VirSorter and phage defence mechanisms using the DefenseFinder tool. Lastly, putative bacteriocins were identified using BAGEL4. Results: The most common community state type (CST) identified across all participants and visits was the highly diverse CST IV, which is dominated by a variety of anaerobes and shows a strong association with BV. In total 3 participants had an optimal, L. crispatus-dominant vaginal microbiota (CST I) across all three study visits and did not use any antibiotics during the study. Samples from these participants yielded a combined 337 isolates. Isolates displayed a wide variety in inhibition potential against P. bivia ATCC 29303T . The isolates selected for further characterisation were all identified as L. crispatus using 16S rRNA sequencing. More than half of the selected isolates inhibited local Prevotella strains more than they inhibited the P. bivia ATCC 29303T type strain. All L. crispatusisolates produced some of each lactic acid isomer, with the top three L-lactate producers all isolated from the same participant (UC101). No correlation was found between the amount of lactate produced and antimicrobial activity against Prevotella strains suggesting that the inhibition was not lactate dependent. All isolates were resistant to metronidazole, but susceptible to other BV and urinary tract infection treatment antibiotics indicating that co administration with metronidazole is a possibility for these candidate probiotic strains. Of the three genomes analysed, two of the isolates harboured plasmids. No previously characterised antimicrobial resistance determinants were identified. Each of the three strains harboured five putative bacteriocins, which may play a role in activity against competing bacterial strains. Additionally, 12 putative prophages were identified, with none found on the plasmid. Overall, seven different potential phage defence mechanisms were identified on the bacterial chromosomes. Conclusion: The proportion of women with longitudinally stable, optimal vaginal communities in our setting was relatively low. However, targeting samples provided by these women for the isolation of potential probiotic bacteria yielded a large number of isolates with inhibitory activity against a BV-associated pathogen. Phenotypic variation among isolates illustrates the importance of screening multiple strains of the same species per sample. The WGS screen did not identify any virulence or antimicrobial resistance genes suggesting that the probiotic candidates are safe to use. The putative bacteriocins found in the isolates could be targeted for future research. This pilot study provides proof-of-principle for a pipeline that will screen L. crispatus strains with probiotic potential from African women to treat BV and improve reproductive health in Africa
Access to acute stroke care: a description of stroke patients' journey to a district hospital
Get PDFIntroduction The burden of stroke in Africa has increased in the last two decades, with the population undergoing a rapid epidemiological transition, with a rise in the incidence of stroke risk factors together with the gradual aging of the population. Evidence-based guidelines for acute stroke care are often not feasible in resource challenged settings but even when resources are available, considerable delays to definitive care exists. This study aims to describe the factors that influence time from symptom onset to hospital arrival in patients that present to a district level hospital Emergency Centre with confirmed ischaemic strokes. Methods A descriptive analysis was performed using retrospective folder and database review. All adult patients with a confirmed ischaemic stroke presenting to Mitchells Plain Hospital Emergency Centre during the study period of 12 months (1st of January 2019 to 31st of December 2019), were eligible for inclusion. Data were collected from existing electronic patient databases and the time from onset of symptoms to hospital arrival was extracted from the clinical notes. Results A total of 730 (2%) patients presented with a diagnosis of stroke, of which 381 (52%) were included (CT confirmed ischaemic strokes). Only 48 (13%) presented within 4.5 hours of symptom onset and the median time from onset of symptoms to presentation to the hospital was 24 hours (IQR 12-72 hours). The majority of patients (31%) arrived via a primary public emergency medical service (EMS) call, while 29% presented directly to the hospital as self-referrals with private transport. Primary public EMS calls had the shortest call-to-hospital-arrival time (1 hour and 31 minutes), even though the median time from symptom onset to hospital arrival was still 16 hours. Conclusion The median time from symptom onset to hospital arrival for patients with stroke symptoms is much longer than what evidence-based guidelines suggest. The chain of survival for emergency stroke care is only as strong as its weakest link and the data from this study suggest that improvement campaigns should target stroke education and access to care
Population pharmacokinetic modelling to optimise treatment for children with Rifampicin-resistant TB and HIV
Get PDFThe global burden of rifampicin- and/or multidrug-resistant (RR/MDR) -TB, i.e. Mycobacterium tuberculosis resistant to rifampicin and/or isoniazid is increasing, especially in settings with high HIV prevalence. Optimising the prevention and treatment of RR/MDR-TB in children in such settings is critically important. Population pharmacokinetic modelling, the state-of-the art technique to interpret pharmacological data, can play a pivotal role for therapeutic optimization in children, since it enables characterisation and inclusion of the effects of important developmental factors, thus allowing for determination and evaluation of effective yet safe RR/MDR treatment in children