ORCID Profile
0000-0002-7162-2590
Current Organisations
University of Melbourne
,
Walter Sisulu University
,
University of Botswana
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Publisher: Elsevier BV
Date: 03-2018
Publisher: Oxford University Press (OUP)
Date: 13-05-2017
DOI: 10.1093/CID/CIX430
Publisher: American Society for Microbiology
Date: 24-08-2020
DOI: 10.1128/JCM.00441-20
Abstract: Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in in iduals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg levels may provide important prognostic information and enable treatment stratification. We performed a laboratory-based validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) against the current gold standard CrAg tests. We assessed the diagnostic accuracy of the CrAgSQ in HIV-positive in iduals undergoing CrAg screening, determined the relationship between CrAgSQ scores and dilutional CrAg titers, assessed interrater reliability, and determined the clinical correlates of CrAgSQ scores.
Publisher: Oxford University Press (OUP)
Date: 04-2020
DOI: 10.1093/CID/CIAA356
Abstract: Evidence to inform cryptococcal antigen (CrAg)–screening guidelines among ART-experienced populations is lacking. We performed a study evaluating the utility of reflex CrAg screening in Gaborone, Botswana. CD4 count data were collected from the HIV reference laboratory from 2014–2016. CrAg screening was performed on s les with CD4 ≤100 cells/µL beginning January 2015. The proportion of CD4 counts ≤100 cells/µL was determined and the frequency of repeat CrAg testing described. Analyses ascertained the impact of ART status on CrAg prevalence and outcomes, and whether CrAg titers could be used for risk stratification. Overall, 5.6% (3335/59 300) of in iduals tested had CD4 ≤100 cells/μL 2108 s les with CD4 ≤100 cells/μL from 1645 unique patients were CrAg tested. Over half of s les were from ART-experienced in iduals: 40.9% (863) on ART and 12.1% (255) defaulters 22% (463) of CrAg tests were on repeat s les. CrAg prevalence was 4.8% (72/1494 95% CI, 3.8–6.0%) among outpatients and 21.9% (32/151 95% CI, 15.3–28.5%) among inpatients. CrAg prevalence rates did not differ by ART status, but 6-month mortality was significantly lower in CrAg-positive in iduals on ART at screening. Ten CrAg positives were identified through repeat testing. A CrAg titer cutoff ≥1:80 provided the best discrimination for 6-month survival. CrAg-positivity rates in an ART-experienced population were comparable to those seen in ART-naive populations. Repeat screening identified in iduals who seroconverted to CrAg positivity and were at risk of cryptococcal disease. CrAg titers ≥1:80 can help identify the in iduals at highest risk of death for more intensive management.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 09-2019
Publisher: IOP Publishing
Date: 08-2022
Abstract: Objective. Retinal prostheses have had limited success in vision restoration through electrical stimulation of surviving retinal ganglion cells (RGCs) in the degenerated retina. This is partly due to non-preferential stimulation of all RGCs near a single stimulating electrode, which include cells that conflict in their response properties and their contribution to visiual processing. Our study proposes a stimulation strategy to preferentially stimulate in idual RGCs based on their temporal electrical receptive fields (tERFs). Approach. We recorded the responses of RGCs using whole-cell patch cl ing and demonstrated the stimulation strategy, first using intracellular stimulation, then via extracellular stimulation. Main results . We successfully reconstructed the tERFs according to the RGC response to Gaussian white noise current stimulation. The characteristics of the tERFs were extracted and compared based on the morphological and light response types of the cells. By re-delivering stimulation trains that were composed of the tERFs obtained from different cells, we could preferentially stimulate in idual RGCs as the cells showed lower activation thresholds to their own tERFs. Significance. This proposed stimulation strategy implemented in the next generation of recording and stimulating retinal prostheses may improve the quality of artificial vision.
Publisher: IOP Publishing
Date: 03-08-2018
Abstract: Retinal prostheses aim to provide visual percepts to blind people affected by diseases caused by photoreceptor degeneration. One of the main challenges presented by current devices is neural adaptation in the retina, which is believed to be the cause of fading-an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to understand the neural adaptation generated in retinal ganglion cells (RGCs) during electrical stimulation. Current visual prostheses use electrical pulses with fixed frequencies and litudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IPI), the latter taken from an exponential distribution. Our observations suggest that stimulation with random IPIs result in lower adaptation rates than stimulation with constant IPIs at frequencies of 50 Hz and 200 Hz. We also found a high proportion of lower litude action potentials, or spikelets. The spikelets were more prominent at high stimulation frequencies (50 Hz and 200 Hz) and were less susceptible to adaptation, but it was not clear if they propagated along the axon. Using random IPI stimulation in retinal prostheses reduces the decay of RGCs and this could potentially reduce fading of electrically induced visual perception.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2019
Publisher: Elsevier BV
Date: 09-2023
Publisher: IOP Publishing
Date: 06-2023
Abstract: Objective . Kalman filtering has previously been applied to track neural model states and parameters, particularly at the scale relevant to electroencephalography (EEG). However, this approach lacks a reliable method to determine the initial filter conditions and assumes that the distribution of states remains Gaussian. This study presents an alternative, data-driven method to track the states and parameters of neural mass models (NMMs) from EEG recordings using deep learning techniques, specifically a long short-term memory (LSTM) neural network. Approach . An LSTM filter was trained on simulated EEG data generated by a NMM using a wide range of parameters. With an appropriately customised loss function, the LSTM filter can learn the behaviour of NMMs. As a result, it can output the state vector and parameters of NMMs given observation data as the input. Main results . Test results using simulated data yielded correlations with R squared of around 0.99 and verified that the method is robust to noise and can be more accurate than a nonlinear Kalman filter when the initial conditions of the Kalman filter are not accurate. As an ex le of real-world application, the LSTM filter was also applied to real EEG data that included epileptic seizures, and revealed changes in connectivity strength parameters at the beginnings of seizures. Significance . Tracking the state vector and parameters of mathematical brain models is of great importance in the area of brain modelling, monitoring, imaging and control. This approach has no need to specify the initial state vector and parameters, which is very difficult to do in practice because many of the variables being estimated cannot be measured directly in physiological experiments. This method may be applied using any NMM and, therefore, provides a general, novel, efficient approach to estimate brain model variables that are often difficult to measure.
Publisher: SAGE Publications
Date: 02-2015
DOI: 10.1016/J.AUSMJ.2014.10.002
Abstract: Research on trust in business collaborations is generally founded on the premises that: a) cognitive trust is initially defined within contractual procedures b) positive experiences lead to adjustments in contractual and/or informal arrangements, and c) cognitive trust is eventually supplanted by affective trust. This dynamic, process view of trust fails to capture the impact of trust experiences in external collaborations on trust emergence in a focal collaboration, and the complexity of trust co-evolution as each actor interprets and responds to the other's communication, behaviour and action. A complexity conceptualisation of trust as a self-organising, adaptive phenomenon can help us better understand the way trust develops. Through engaging with complexity theories as metaphors to enrich trust theory, trust is described as ‘self-organising’ as new cognitive, interpretive schema are evoked, and ‘adapting’ in response to trust experiences external to the collaboration. A complexity perspective evokes a new field of research questions and rich methodological opportunities.
Publisher: Oxford University Press (OUP)
Date: 23-10-2018
DOI: 10.1093/OFID/OFY267
Abstract: Cryptococcal meningitis (CM) causes 10%–20% of HIV-related deaths in Africa. Due to limited access to liposomal hotericin and flucytosine, most African treatment guidelines recommend hotericin B deoxycholate (AmB-d) plus high-dose fluconazole outcomes with this treatment regimen in routine care settings have not been well described. Electronic national death registry data and computerized medical records were used to retrospectively collect demographic, laboratory, and 1-year outcome data from all patients with CM between 2012 and 2014 at Botswana’s main referral hospital, when recommended treatment for CM was AmB-d 1 mg/kg/d plus fluconazole 800 mg/d for 14 days. Cumulative survival was estimated at 2 weeks, 10 weeks, and 1 year. There were 283 episodes of CM among 236 in iduals 69% (163/236) were male, and the median age was 36 years. All patients were HIV-infected, with a median CD4 count of 39 cells/mm3. Two hundred fifteen person-years of follow-up data were captured for the 236 CM patients. Complete outcome data were available for 233 patients (99%) at 2 weeks, 224 patients (95%) at 10 weeks, and 219 patients (93%) at 1 year. Cumulative mortality was 26% (95% confidence interval [CI], 20%–32%) at 2 weeks, 50% (95% CI, 43%–57%) at 10 weeks, and 65% (95% CI, 58%–71%) at 1 year. Mortality rates following HIV-associated CM treated with AmB-d and fluconazole in a routine health care setting in Botswana were very high. The findings highlight the inadequacies of current antifungal treatments for HIV-associated CM and underscore the difficulties of administering and monitoring intravenous hotericin B deoxycholate therapy in resource-poor settings.
Publisher: Oxford University Press (OUP)
Date: 22-11-2022
DOI: 10.1093/JAC/DKAC389
Abstract: Single, high-dose liposomal hotericin B (LAmB AmBisome, Gilead Sciences) has demonstrated non-inferiority to hotericin B deoxycholate in combination with other antifungals for averting all-cause mortality from HIV-associated cryptococcal meningitis. There are limited data on the pharmacokinetics (PK) of AmBisome. The aim of this study was to describe population PK of AmBisome and conduct a meta-analysis of the available studies to suggest the optimal dosing for cryptococcal meningoencephalitis. Data from a Phase II and Phase III trial of high-dose, short-course AmBisome for cryptococcal meningoencephalitis were combined to develop a population PK model. A search was conducted for trials of AmBisome monotherapy and meta-analysis of clinical outcome data was performed. A two-compartment model with first-order clearance of drug from the central compartment fitted the data best and enabled the extent of inter-in idual variability in PK to be quantified. Mean (SD) population PK parameter estimates were: clearance 0.416 (0.363) L/h volume of distribution 4.566 (4.518) L first-order transfer of drug from central to peripheral compartments 2.222 (3.351) h−1, and from peripheral to central compartment 2.951 (4.070) h−1. Data for the meta-analysis were insufficient to suggest optimal dosing of AmBisome for cryptococcal meningoencephalitis. This study provides novel insight into the PK of AmBisome at the population level and the variability therein. Our analysis also serves to highlight the paucity of data available on the pharmacodynamics (PD) of AmBisome and underscores the importance of thorough and detailed PK/PD analysis in the development of novel antifungals, by demonstrating the challenges associated with post hoc PK/PD analysis.
No related grants have been discovered for Artemio Soto-Breceda.