Temporal Passage: Dynamic Experiences and the B-theory

I take the problem presented by McTaggart (1908) and by more recent A-theorists to be that the B-theory cannot account for our experience of change in virtue of not accepting temporal passage. Accordingly, the goal of my thesis is to show that the B-theorist can account for our experience, whether or not they think that time really passes. I begin with a discussion of tensed language and, specifically, the claim levelled against B-theorists that they cannot even account for our use of tensed language or our holding of tensed beliefs. That is, the problem is meant to be that B-theorists cannot account for the true meaning of tensed sentences because they do not accept that there are any tensed propositions. I argue that the B-theorist is equipped with two plausible solutions. They can either hold that tensed sentences are context-sensitive - i.e. are used differently to tenseless ones depending on the time at which they are uttered, or they can hold that the content of a belief is really a property – i.e. a world, a time, and an individual. However, I argue that just an account of tensed language does not get the B-theorist out of trouble. They still need an account of why it is that we use tensed sentences – that is, they need an account of our tensed experience or what I call our experience of phenomenal temporal passage. Then, in the next chapter, I provide a projectivist account for the B-theorist who thinks that we have illusory perceptions of this phenomenal experience as existing mind-independently. The view is that we project our experience of phenomenal temporal passage onto the world and have the illusory perception that phenomenal temporal passage exists mind-independently. I argue that projectivism adequately accounts for our experience of phenomenal passage. However, the view will only be appealing to theorists who are willing to accept that we are subject to massive illusion. Accordingly, I will explore views according to which our experience of passage is just part of experiencing mind-independent features or properties. These B-passage views identify temporal passage as some part of the mind-independent B-theoretic structure (e.g. causal order or the existence of times). I argue that, while these views provide good accounts of temporal passage on the B-theory, I think that we need an account of, not only temporal passage on the B-theory, but also of our experience of phenomenal temporal passage. Specifically, I think we need a view according to which our experience is an expected outcome of mind-independent features. I think dispositionalism achieves this. Dispositionalism is the view according to which temporal passage is a mind-independent disposition to result in our experience of phenomenal temporal passage. In the thesis, I will explain why I think dispositionalists can account for phenomenal temporal passage as an expected outcome of mind-independent features and is, therefore, the more intuitive view. However, I will conclude that each of the views discussed adequately accounts for our experience – they differ only in what they accept in order to do so.Thesis (MPhil) -- University of Adelaide, School of Humanities, 202

Moving ego versus moving time : investigating the shared source of future-bias and near-bias

It has been hypothesized that our believing that, or its seeming to us as though, the world is in some way dynamical partially explains (and perhaps rationalizes) future-bias. Recent work has, in turn, found a correlation between future-bias and near-bias, suggesting that there is a common explanation for both. Call the claim that what partially explains our being both future- and near-biased is our believing/it seeming to us as though the world is dynamical, the dynamical explanation. We empirically test two versions of the dynamical explanation. The first is the moving ego explanation—according to which it is our belief that the ego moves, or our phenomenology as of the ego moving, that jointly (partially) explains future- and near-bias. The second is the moving time explanation—according to which it is our belief that time robustly passes, or our phenomenology as of robust passage, which jointly (partially) explain future- and near-bias. We found no evidence in favour of either explanation

Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998-2017)

Background The adequacy of the WHO Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. Methods We determined the change in population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998-2017). AMR profiles were assessed by the disc diffusion method and trends over time were evaluated. Results A total 89,643 pediatric blood cultures were performed, and 10,621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1,000 persons in 2002 to 3.4 per 1,000 persons in 2017. Over two decades, resistance of Gram-negative pathogens to all empiric first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (p<0.001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (p<0.001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (p<0.001). Conclusions The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens resistant to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly expanding AMR in childhood BSI

Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998-2016): a surveillance study.

BACKGROUND Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance. METHODS In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time. FINDINGS Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016. INTERPRETATION The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting. FUNDING Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE)

Invasive Streptococcus pneumoniae in Children, Malawi, 2004–2006

Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible

Cheat Sheets for Data Visualization Techniques

This paper introduces the concept of ‘cheat sheets’ for data visualization techniques, a set of concise graphical explanations and textual annotations inspired by infographics, data comics, and cheat sheets in other domains. Cheat sheets aim to address the increasing need for accessible material that supports a wide audience in understanding data visualization techniques, their use, their fallacies and so forth. We have carried out an iterative design process with practitioners, teachers and students of data science and visualization, resulting six types of cheat sheet (anatomy, construction, visual patterns, pitfalls, false-friends and well-known relatives) for six types of visualization, and formats for presentation. We assess these with a qualitative user study using 11 participants that demonstrates the readability and usefulness of our cheat sheets

Modelling the Contributions of Malaria, HIV, Malnutrition and Rainfall to the Decline in Paediatric Invasive Non-typhoidal Salmonella Disease in Malawi.

INTRODUCTION: Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition. METHODS: Trends in monthly numbers of childhood iNTS disease presenting at Queen's Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM). RESULTS: Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence. CONCLUSIONS: These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions

Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages

Objectives ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. Methods We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Results Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. Conclusions There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations

Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

OBJECTIVE: To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. METHODS: Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. RESULTS: 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = -0.91; p<0.001). CONCLUSION: During 2004-2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes