Understanding the temporal dynamics of visual hallucinations in Parkinson's Disease with dementia

PhD ThesisBackground Integrative models of visual hallucinations (VH) posit that the symptom requires disruptions to both bottom-up and top-down visual processing. Although many lines of evidence point to a mixture of aberrant processing and disconnection between key nodes in the visual system, in particular the dorsal and ventral attention networks, there have been no attempts to understand the dynamic behaviour of these systems in Parkinson’s disease with dementia (PDD) with VH. Aims The primary aim of this thesis was to explore the correlates of synaptic communication in the visual system and how spatio-temporal dynamics of the early visual system are altered in relation to the severity of VH. The secondary aim was to help understand the balance between the contributions of bottom-up and top-down processing for the experience of VH in PDD. Methods An assortment of investigative approaches, including resting state electroencephalography (EEG), visual evoked potentials (VEPs), and concurrent EEG and transcranial magnetic stimulation (TMS) were applied in a group of PDD patients with a range of VH severities (n = 26) and contrasted with a group of age matched healthy controls (n = 17). Results Latency of the N1 component was similar between groups, suggesting intact transfer between the retina and the cortex. However, PDD patients had an inherent reduction in the amplitude of the VEP components and displayed a pattern of declining P1 latencies in association with more frequent and severe VH. Evoked potentials arising from TMS of the striate cortex were similar in amplitude and latency for each of the components between PDD and controls. However, inter-component activity at several stages was altered in the PDD group, whilst the frequency and severity of VH was positively associated with the amplitudes of several components in the occipital and parietal regions. Finally, attentional modulation as measured by the alpha-band reactivity was also compromised in PDD patients. iv Conclusions These data provide neurophysiological evidence that both early bottom-up and top-down dysfunctions of the visual system occur in PDD patients who hallucinate, thus supporting integrative models of VH.National Institute for Health Research (NIHR) Biomedical Research Unit (BRU)

Partial outpatient oral antibiotic treatment of infective endocarditis is non-inferior to inpatient intravenous antibiotic therapy

A clinical decision report using: Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019; 380:415-424. https://doi.org/10.1056/NEJMoa1808312 for a patient with infective endocarditis and intravenous drug use with desire to leave the hospital

An online learning algorithm for technical trading

We use an adversarial expert based online learning algorithm to learn the optimal parameters required to maximise wealth trading zero-cost portfolio strategies. The learning algorithm is used to determine the relative population dynamics of technical trading strategies that can survive historical back-testing as well as form an overall aggregated portfolio trading strategy from the set of underlying trading strategies implemented on daily and intraday Johannesburg Stock Exchange data. The resulting population time-series are investigated using unsupervised learning for dimensionality reduction and visualisation. A key contribution is that the overall aggregated trading strategies are tested for statistical arbitrage using a novel hypothesis test proposed by Jarrow et al. [31] on both daily sampled and intraday time-scales. The (low frequency) daily sampled strategies fail the arbitrage tests after costs, while the (high frequency) intraday sampled strategies are not falsified as statistical arbitrages after costs. The estimates of trading strategy success, cost of trading and slippage are considered along with an offline benchmark portfolio algorithm for performance comparison. In addition, the algorithms generalisation error is analysed by recovering a probability of back-test overfitting estimate using a nonparametric procedure introduced by Bailey et al. [19]. The work aims to explore and better understand the interplay between different technical trading strategies from a data-informed perspective

Heroin type, injecting behavior, and HIV transmission. A simulation model of HIV incidence and prevalence.

Background and aimsUsing mathematical modeling to illustrate and predict how different heroin source-forms: "black tar" (BTH) and powder heroin (PH) can affect HIV transmission in the context of contrasting injecting practices. By quantifying HIV risk by these two heroin source-types we show how each affects the incidence and prevalence of HIV over time. From 1997 to 2010 PH reaching the United States was manufactured overwhelmingly by Colombian suppliers and distributed in the eastern states of the United States. Recently Mexican cartels that supply the western U.S. states have started to produce PH too, replacing Colombian distribution to the east. This raises the possibility that BTH in the western U.S. may be replaced by PH in the future.DesignWe used an agent-based model to evaluate the impact of use of different heroin formulations in high- and low-risk populations of persons who inject drugs (PWID) who use different types of syringes (high vs. low dead space) and injecting practices. We obtained model parameters from peer-reviewed publications and ethnographic research.ResultsHeating of BTH, additional syringe rinsing, and subcutaneous injection can substantially decrease the risk of HIV transmission. Simulation analysis shows that HIV transmission risk may be strongly affected by the type of heroin used. We reproduced historic differences in HIV prevalence and incidence. The protective effect of BTH is much stronger in high-risk compared with low-risk populations. Simulation of future outbreaks show that when PH replaces BTH we expect a long-term overall increase in HIV prevalence. In a population of PWID with mixed low- and high-risk clusters we find that local HIV outbreaks can occur even when the overall prevalence and incidence are low. The results are dependent on evidence-supported assumptions.ConclusionsThe results support harm-reduction measures focused on a reduction in syringe sharing and promoting protective measures of syringe rinsing and drug solution heating

PLEP-0001 – Purpose and Guidelines for PlasmaPy Enhancement Proposals

PlasmaPy Enhancement Proposals (PLEPs) are design documents that provide information to the PlasmaPy community, describe decision-making processes, or propose major changes or enhancements to the code. PLEPs are intended to be the primary mechanism for proposing major changes to the direction of PlasmaPy, collecting community feedback, and documenting the reasoning behind major decisions. This document describes the process for creating and deciding upon PLEPs

Pathways for Nutrient Loss to Water; Slurry and Fertilizer Spreading

End of project reportThere are almost 150,000 farms in Ireland and these contribute substantial quantities of N and P to inland and coastal waters. Some of these nutrients are carried from wet soils by overland flow and by leaching from dry soils. Farm practice can reduce the loss from farms by judicious management of nutrients. Improvements are required to diminish export of nutrients without impairing operations on the farm. Literature regarding nutrient loss from agriculture was reviewed in this project and maps were prepared to predict best slurry spreading times around Ireland. Two further maps were prepared to show slurry storage requirement on farms