412 research outputs found
Murlin Croucher: Magician of Slavic Book Collecting
No full textMemorial article in honor of Murlin Croucher, long time Slavic bibliographer at Indiana University. Includes reminiscence of the author and excerpts from letters written by Murlin Croucher
Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines
No full textOf over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.Open Acces
Atlantic Guardian, vol. 02, no. 07 (July 1946)
No full textOur fate is sealed / Ottawa Journal -- The outport millionaire / Ron Pollett -- Newfoundland's place in communications / L. R. Croucher -- Oh, to be in Newfoundland / Nat A. Boynton (plus five pages of pictures -- Heart's Content / E. H. Hopkins -- Guardian angles -- The editor's page.A popular magazine covering Newfoundland news and human interest stories with features such as Newfoundlanders Abroad, the Baby of the Month and community profiles, as well as poetry and short stories. Heavily illustrated with photographs. -- "Atlantic Guardian's platform: to make Newfoundland better known at home and abroad; to promote trade and travel in the Island; to encourage development of the Island's natural resources; to foster good relations between Newfoundland and her neighbors" (on all title pages after vol. 1, no. 4).Published monthly 1945-57, thereafter absorbed by the Atlantic Advocate (1952-92); suspended publication: October 1952-May 1953. Missing issues: vol. 14, nos. 7-8. -- An index to vols. 1-10 by author and/or article type is in vol. 11, no. 1 (January-February 1954), p. 33-48
The molecular ecology of cryptococcus neoformans and cryptococcus gattii in Zambia - implications for clinical epidemiology, virulence and drug resistance
No full textUnderstanding the distribution and population genomics of sapronoses in the environment can lend important insights into their clinical threat. Environmental Cryptococcus neoformans and Cryptococcus gattii isolates in Zambia collected in 2013/14 revealed a north-south ecological divide of the two species complexes, high diversity of molecular types, and clinical phenotype enrichment in VNB-II. However, the number of environmental genomes available for analysis was limited and analytical methods can be improved.
To address this, additional environmental isolates were collected in 2019 to better understand the molecular epidemiology, species distribution and niche preference of C. neoformans and C. gattii in Zambia. Combined analysis of 2013/14 and 2019 isolates revealed high environmental diversity, but a paucity of the main clinical threat, VNI, and abundance of lineages of less clinical significance (VNB and C. gattii). Chromosome copy number variation was identified as an important adaptation mechanism observed solely in clinical C. neoformans isolates. Phenotyping assays suggested clinical VNI to be more heavily melanised, although melanisation was associated with a loss of fitness. Tolerance and heteroresistance to fluconazole were observed in environmental isolates, suggesting these to be inherent internal mechanisms. SDM largely supported an ecological split between the two species complexes, but for the first time this was attributed in large part to soil mineral composition as opposed to climate factors. Hyrax middens were confirmed as preferred niches for C. gattii, but C. neoformans was also identified here for the first time. Analysis of ancient hyrax midden samples suggested possible presence of cryptococcal genomes up to 60,000 calibrated years before the present. First attempts, to our knowledge, of air sampling in Zambia could not confirm presence of aerosolised cryptococcal spores. Findings have implications for geographic risk stratification to inform diagnostic practices, knowledge of occupied niches, and mechanisms of virulence as well as antifungal resistance and tolerance.Open Acces
Evaluation of machine learning algorithms for predictive modelling of antibiotic resistance using genomic and spatiotemporal data
No full textThe discovery of antibiotics transformed public health, as previously life-threatening
bacterial diseases became treatable. However, the selection pressure created by the
widespread use of antibiotics promoted the expansion of many antibiotic resistant
bacterial lineages. Additionally, since the “golden age of antibiotic discovery” (c.1950-
1970), the rate of discovery of novel antibiotics has steeply declined. This compounds
the major public health threat posed by the phenomenon of antibiotic resistance.
To limit the further dissemination of antibiotic resistant bacteria, and improve patient
health outcomes, predictive models could be developed to assist clinicians and public
health agencies in decision making. Here, I consider two distinct applications of machine
learning for predictive modelling in this field:
• Prediction of the antibiotic resistance phenotype of bacterial lineages using
genomic data.
• Forecasting of the future prevalence of antibiotic resistance from surveillance
data.
Across these two related areas I made the following contributions to the field. Firstly, I
established robust protocols for evaluating these models, and demonstrate that without
this it is difficult to fairly evaluate the performance of these models. Secondly, I present
alternative methods for designing predictive models of bacterial phenotype which
generalise accurately across populations, and investigate the utility of conditioning
these models on a graph representation of the bacterial pangenome. Thirdly, I compare
approaches for forecasting the future prevalence of antibiotic resistance in different
species, including different models and data types.
I conclude that there is potential for machine learning to be very impactful in this
setting. However, to maximise this impact more appropriate datasets with which to train
and evaluate predictive models of antibiotic resistance need to be collated. In the final
chapter I describe what I believe to be the key features of an appropriate data collection
protocol to support the development of these models.Open Acces
Whole genome alignments of 15 sequence clusters of similar isolates
No full textFifteen FASTA format whole genome alignments, each corresponding to one of the monophyletic sequence clusters identified through population clustering and phylogenetics as described in Croucher et al (2013) Nat. Genet. 45:656-663. Alignments were generated through mapping of paired Illumina reads to a reference sequence, itself omitted from the alignment, using SMALT. Files are compressed as a single archive using tar and gzip
The narrative/storytelling approach in brand development for towns
No full textThe narrative or storytelling approach is often associated with folklore and other aspects of socialisation rather than a scientific and systematic approach to conceptualising a phenomenon. However, there is a growing body of literature centred on both the practical applications and relevant theory on the authenticity of applying the storytelling approach in brand development and there is evidence to prove the efficacy of this approach in the process. Denning (2007) demonstrates the application of the narrative in general management and branding. Boje (2006; 2008) highlights the story as a reflection of the respective entity in any given situation, be it the individual, the department or the organisation. In formulating a conceptual frame on the application of storytelling in brand development for towns this paper focuses on four key variables which are a) the history of the town, b) the criteria for effective branding, c) the narrative approach in brand building and d) the town strategy for growth, infrastructure, geography.
Lucado(2005) presents the s.t.o.r.y as representing strengths, topic, optimal conditions, relationship and yes. This logical flow of developments shows that the whole process will consolidate a given phenomenon. Ultimately the narrative-based brand development approach concludes that all phenomenon is centred on the story, and the effectiveness of the brand depends on the management of the story in conjunction with the marketing concept and its related variables
Women, work and war : industrial mobilisation and demobilisation, Coventry and Bolton, 1940-1946
No full textThe emphasis in this thesis is on women's popular
attitudes towards the two processes of industrial mobilisation
and demobilisation which took place between 1940 and 1946.
Although the work includes a survey of the national picture of
those two processes, it concentrates on case studies in two towns
which exhibited different characteristics of women's employment,
Coventry and Bolton. This is done in an attempt to see if the
tradition of women's employment affected their attitudes towards
war work. In Coventry, the best sources of women's employment
were for single women. During the nineteen-thirties it was obvious
that the motor industry employed increasing numbers of women, but, again,
the unmarried. The economic participation rate in Coventry was slightly
lower than the national average. On the other hand, the cotton industry
in Bolton customarily had engaged married women as well as single women,
therefore, the women's economic participation rate was about 10 per cent.
higher than the national average. Local custom with regard to married
women's employment appears to have affected women's ideas About their
domestic responsibilities. Coventry women were more reserved and more
conscious of their domestic role. However, the comparison between the
two towns also brought out similarities as well as differences in women's
attitudes to industrial mobilisation. During demobilisation, the
similarities between Coventry and Bolton were more strongly marked.
The majority of women war workers had no intention of staying on in the
factory, in jobs which were still largely thought of as 'men's work'.
Most women thought that their well-being was dependent on men's secure
employment and high wages. They did not want to do anything to threaten
it. There seems to have been little antagonism between men and women
during the mobilisation and demobilisation period
The evolution of multi-strain bacterial populations
No full textNon UBCUnreviewedAuthor affiliation: Imperial College LondonResearche
Examining recombination and intra-genomic conflict dynamics in the evolution of anti-microbial resistant bacteria
No full textThe spread of antimicrobial resistance (AMR) among pathogenic bacterial species threatens to undercut much of the progress made in treating infectious diseases. AMR genes can disseminate between and within populations via horizontal gene transfer (HGT). Selfish mobile genetic elements (MGEs) can encode resistance and spread between host cells. Homologous recombination can alter the core genes of pathogens with resistant donors via HGT too. MGEs may be cured from host genomes through transformation. Hence, MGEs may be able to avoid deletion by disrupting transformation. This work aims to understand how the dynamics of these processes affect the epidemiology of AMR pathogens.
To understand these dynamics, I co-developed a new version of the popular recombination detection tool Gubbins. Through simulation studies, I find this new version to be both accurate in reconstructing the relationships between isolates, and efficient in terms of its use of computational resources.
I then apply Gubbins to both AMR lineages and species-wide datasets of the pathogen Streptococcus pneumoniae. I find that recombination frequently occurs around core genes involved in both drug resistance and the host immune response. Additionally, an MGE was able to successfully spread within a population by disrupting the transformation machinery, preventing its loss from the host.
Finally, I investigate two recent examples of MGEs disrupting transformation in the gram-negative species Acinetobacter baumannii and Legionella pneumophila. I find that while these insertions may decrease the efficiency of transformations within cells, the observed recombination rates largely reflect the selection pressures on isolates. With MGEs only partially able to inhibit these observable transformation events.
These results show how selection pressures from clinical interventions shape pathogen genomes through diverse, often interspecies, recombination events. The spread of MGEs can also be favoured by both these selection pressures, and their ability to disrupt host cell machinery.Open Acces
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